array:24 [
  "pii" => "S2254887418300122"
  "issn" => "22548874"
  "doi" => "10.1016/j.rceng.2017.12.004"
  "estado" => "S300"
  "fechaPublicacion" => "2018-03-01"
  "aid" => "1457"
  "copyright" => "Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI)"
  "copyrightAnyo" => "2017"
  "documento" => "article"
  "crossmark" => 1
  "subdocumento" => "fla"
  "cita" => "Rev Clin Esp. 2018;218:74-88"
  "abierto" => array:3 [
    "ES" => false
    "ES2" => false
    "LATM" => false
  ]
  "gratuito" => false
  "lecturas" => array:2 [
    "total" => 9
    "formatos" => array:2 [
      "HTML" => 5
      "PDF" => 4
    ]
  ]
  "Traduccion" => array:1 [
    "es" => array:19 [
      "pii" => "S0014256517302886"
      "issn" => "00142565"
      "doi" => "10.1016/j.rce.2017.12.003"
      "estado" => "S300"
      "fechaPublicacion" => "2018-03-01"
      "aid" => "1457"
      "copyright" => "Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI)"
      "documento" => "article"
      "crossmark" => 1
      "subdocumento" => "fla"
      "cita" => "Rev Clin Esp. 2018;218:74-88"
      "abierto" => array:3 [
        "ES" => false
        "ES2" => false
        "LATM" => false
      ]
      "gratuito" => false
      "lecturas" => array:2 [
        "total" => 380
        "formatos" => array:2 [
          "HTML" => 226
          "PDF" => 154
        ]
      ]
      "es" => array:13 [
        "idiomaDefecto" => true
        "cabecera" => "<span class="elsevierStyleTextfn">ART&#205;CULO ESPECIAL</span>"
        "titulo" => "Tratamiento de la diabetes mellitus tipo 2 en el paciente anciano"
        "tienePdf" => "es"
        "tieneTextoCompleto" => "es"
        "tieneResumen" => array:2 [
          0 => "es"
          1 => "en"
        ]
        "paginas" => array:1 [
          0 => array:2 [
            "paginaInicial" => "74"
            "paginaFinal" => "88"
          ]
        ]
        "titulosAlternativos" => array:1 [
          "en" => array:1 [
            "titulo" => "Treatment of type 2 diabetes mellitus in elderly patients"
          ]
        ]
        "contieneResumen" => array:2 [
          "es" => true
          "en" => true
        ]
        "contieneTextoCompleto" => array:1 [
          "es" => true
        ]
        "contienePdf" => array:1 [
          "es" => true
        ]
        "resumenGrafico" => array:2 [
          "original" => 0
          "multimedia" => array:7 [
            "identificador" => "fig0005"
            "etiqueta" => "Figura 1"
            "tipo" => "MULTIMEDIAFIGURA"
            "mostrarFloat" => true
            "mostrarDisplay" => false
            "figura" => array:1 [
              0 => array:4 [
                "imagen" => "gr1.jpeg"
                "Alto" => 1478
                "Ancho" => 2506
                "Tamanyo" => 264090
              ]
            ]
            "descripcion" => array:1 [
              "es" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Algoritmo del tratamiento de la diabetes mellitus tipo2 en el paciente anciano&#46;</p> <p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">arGLP1&#58; agonistas del receptor del <span class="elsevierStyleItalic">glucagon-like peptide-1&#59;</span> iDPP4&#58; inhibidores de la dipeptidil peptidasa-4&#59; iSGLT2&#58; inhibidores del cotransportador sodio-glucosa tipo 2&#46;</p> <p id="spar0035" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">a</span> Repaglinida y pioglitazona pueden emplearse en pacientes con FG &#60; 30 ml&#47;min&#44; pero su uso no es recomendable por el riesgo de efectos adversos&#58; hipoglucemias &#40;repaglinida&#41;&#59; retenci&#243;n hidrosalina&#44; insuficiencia cardiaca y fracturas &#40;pioglitazona&#41;&#46;</p> <p id="spar0040" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">b</span> Empagliflozina&#44; canagliflozina y liraglutida han demostrado reducci&#243;n de la morbimortalidad cardiovascular en pacientes con diabetes tipo 2 de alto riesgo vascular&#46;</p> <p id="spar0045" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">c</span> Saxagliptina deben evitarse en pacientes con insuficiencia cardiaca&#46;</p> <p id="spar0050" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">d</span> Pioglitazona est&#225; contraindicada en pacientes con insuficiencia cardiaca o en riesgo de fracturas&#46;</p>"
            ]
          ]
        ]
        "autores" => array:1 [
          0 => array:2 [
            "autoresLista" => "R&#46; G&#243;mez-Huelgas, F&#46; G&#243;mez Peralta, L&#46; Rodr&#237;guez Ma&#241;as, F&#46; Formiga, M&#46; Puig Domingo, J&#46;J&#46; Mediavilla Bravo, C&#46; Miranda, J&#46; Ena"
            "autores" => array:8 [
              0 => array:2 [
                "nombre" => "R&#46;"
                "apellidos" => "G&#243;mez-Huelgas"
              ]
              1 => array:2 [
                "nombre" => "F&#46;"
                "apellidos" => "G&#243;mez Peralta"
              ]
              2 => array:2 [
                "nombre" => "L&#46;"
                "apellidos" => "Rodr&#237;guez Ma&#241;as"
              ]
              3 => array:2 [
                "nombre" => "F&#46;"
                "apellidos" => "Formiga"
              ]
              4 => array:2 [
                "nombre" => "M&#46;"
                "apellidos" => "Puig Domingo"
              ]
              5 => array:2 [
                "nombre" => "J&#46;J&#46;"
                "apellidos" => "Mediavilla Bravo"
              ]
              6 => array:2 [
                "nombre" => "C&#46;"
                "apellidos" => "Miranda"
              ]
              7 => array:2 [
                "nombre" => "J&#46;"
                "apellidos" => "Ena"
              ]
            ]
          ]
        ]
      ]
      "idiomaDefecto" => "es"
      "Traduccion" => array:1 [
        "en" => array:9 [
          "pii" => "S2254887418300122"
          "doi" => "10.1016/j.rceng.2017.12.004"
          "estado" => "S300"
          "subdocumento" => ""
          "abierto" => array:3 [
            "ES" => false
            "ES2" => false
            "LATM" => false
          ]
          "gratuito" => false
          "lecturas" => array:1 [
            "total" => 0
          ]
          "idiomaDefecto" => "en"
          "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2254887418300122?idApp=WRCEE"
        ]
      ]
      "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0014256517302886?idApp=WRCEE"
      "url" => "/00142565/0000021800000002/v1_201802240414/S0014256517302886/v1_201802240414/es/main.assets"
    ]
  ]
  "itemSiguiente" => array:19 [
    "pii" => "S2254887417301376"
    "issn" => "22548874"
    "doi" => "10.1016/j.rceng.2017.11.001"
    "estado" => "S300"
    "fechaPublicacion" => "2018-03-01"
    "aid" => "1450"
    "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46; and Sociedad Espa&#241;ola de Medicina Interna &#40;SEMI&#41;"
    "documento" => "article"
    "crossmark" => 1
    "subdocumento" => "ssu"
    "cita" => "Rev Clin Esp. 2018;218:89-97"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:2 [
      "total" => 2
      "PDF" => 2
    ]
    "en" => array:13 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Review</span>"
      "titulo" => "Characteristics of patients with myelomatous pleural effusion&#46; A systematic review"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "es"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "89"
          "paginaFinal" => "97"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Caracter&#237;sticas de los pacientes con derrame pleural mielomatoso&#46; Revisi&#243;n sistem&#225;tica"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "es" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig0005"
          "etiqueta" => "Figure 1"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr1.jpeg"
              "Alto" => 1672
              "Ancho" => 2667
              "Tamanyo" => 218564
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">PRISMA flow diagram of the reviewed literature&#46; Abbreviation&#58; PRISMA&#44; Preferred Reporting Items for Systematic reviews and Meta-Analyses&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "V&#46; Riveiro, L&#46; Ferreiro, M&#46;E&#46; Toubes, A&#46; Lama, J&#46;M&#46; &#193;lvarez-Doba&#241;o, L&#46; Vald&#233;s"
          "autores" => array:6 [
            0 => array:2 [
              "nombre" => "V&#46;"
              "apellidos" => "Riveiro"
            ]
            1 => array:2 [
              "nombre" => "L&#46;"
              "apellidos" => "Ferreiro"
            ]
            2 => array:2 [
              "nombre" => "M&#46;E&#46;"
              "apellidos" => "Toubes"
            ]
            3 => array:2 [
              "nombre" => "A&#46;"
              "apellidos" => "Lama"
            ]
            4 => array:2 [
              "nombre" => "J&#46;M&#46;"
              "apellidos" => "&#193;lvarez-Doba&#241;o"
            ]
            5 => array:2 [
              "nombre" => "L&#46;"
              "apellidos" => "Vald&#233;s"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "es" => array:9 [
        "pii" => "S0014256517302618"
        "doi" => "10.1016/j.rce.2017.11.001"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => false
          "ES2" => false
          "LATM" => false
        ]
        "gratuito" => false
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "es"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0014256517302618?idApp=WRCEE"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2254887417301376?idApp=WRCEE"
    "url" => "/22548874/0000021800000002/v1_201802230423/S2254887417301376/v1_201802230423/en/main.assets"
  ]
  "itemAnterior" => array:19 [
    "pii" => "S2254887418300249"
    "issn" => "22548874"
    "doi" => "10.1016/j.rceng.2018.01.003"
    "estado" => "S300"
    "fechaPublicacion" => "2018-03-01"
    "aid" => "1466"
    "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46; and Sociedad Espa&#241;ola de Medicina Interna &#40;SEMI&#41;"
    "documento" => "simple-article"
    "crossmark" => 1
    "subdocumento" => "edi"
    "cita" => "Rev Clin Esp. 2018;218:72-3"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:2 [
      "total" => 1
      "PDF" => 1
    ]
    "en" => array:10 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Editorial</span>"
      "titulo" => "Clinical scales&#58; Tools for the diagnosis of unstable angina"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "72"
          "paginaFinal" => "73"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Escalas cl&#237;nicas&#58; una herramienta para el diagn&#243;stico de angina inestable"
        ]
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "A&#46; Alqu&#233;zar-Arb&#233;, B&#46; Lopez Barbeito"
          "autores" => array:2 [
            0 => array:2 [
              "nombre" => "A&#46;"
              "apellidos" => "Alqu&#233;zar-Arb&#233;"
            ]
            1 => array:2 [
              "nombre" => "B&#46;"
              "apellidos" => "Lopez Barbeito"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "es" => array:9 [
        "pii" => "S0014256518300250"
        "doi" => "10.1016/j.rce.2018.01.005"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => false
          "ES2" => false
          "LATM" => false
        ]
        "gratuito" => false
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "es"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0014256518300250?idApp=WRCEE"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2254887418300249?idApp=WRCEE"
    "url" => "/22548874/0000021800000002/v1_201802230423/S2254887418300249/v1_201802230423/en/main.assets"
  ]
  "en" => array:20 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Special article</span>"
    "titulo" => "Treatment of type 2 diabetes mellitus in elderly patients"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "74"
        "paginaFinal" => "88"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "R&#46; G&#243;mez-Huelgas, F&#46; G&#243;mez Peralta, L&#46; Rodr&#237;guez Ma&#241;as, F&#46; Formiga, M&#46; Puig Domingo, J&#46;J&#46; Mediavilla Bravo, C&#46; Miranda, J&#46; Ena"
        "autores" => array:8 [
          0 => array:4 [
            "nombre" => "R&#46;"
            "apellidos" => "G&#243;mez-Huelgas"
            "email" => array:1 [
              0 => "ricardogomezhuelgas&#64;hotmail&#46;com"
            ]
            "referencia" => array:5 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
              2 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">c</span>"
                "identificador" => "aff0015"
              ]
              3 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">d</span>"
                "identificador" => "aff0020"
              ]
              4 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "F&#46;"
            "apellidos" => "G&#243;mez Peralta"
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">e</span>"
                "identificador" => "aff0025"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">f</span>"
                "identificador" => "aff0030"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "L&#46;"
            "apellidos" => "Rodr&#237;guez Ma&#241;as"
            "referencia" => array:3 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">g</span>"
                "identificador" => "aff0035"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">h</span>"
                "identificador" => "aff0040"
              ]
              2 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">i</span>"
                "identificador" => "aff0045"
              ]
            ]
          ]
          3 => array:3 [
            "nombre" => "F&#46;"
            "apellidos" => "Formiga"
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">j</span>"
                "identificador" => "aff0050"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">k</span>"
                "identificador" => "aff0055"
              ]
            ]
          ]
          4 => array:3 [
            "nombre" => "M&#46;"
            "apellidos" => "Puig Domingo"
            "referencia" => array:4 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">l</span>"
                "identificador" => "aff0060"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">m</span>"
                "identificador" => "aff0065"
              ]
              2 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">n</span>"
                "identificador" => "aff0070"
              ]
              3 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#241;</span>"
                "identificador" => "aff0075"
              ]
            ]
          ]
          5 => array:3 [
            "nombre" => "J&#46;J&#46;"
            "apellidos" => "Mediavilla Bravo"
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">o</span>"
                "identificador" => "aff0080"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">p</span>"
                "identificador" => "aff0085"
              ]
            ]
          ]
          6 => array:3 [
            "nombre" => "C&#46;"
            "apellidos" => "Miranda"
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">q</span>"
                "identificador" => "aff0090"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">r</span>"
                "identificador" => "aff0095"
              ]
            ]
          ]
          7 => array:3 [
            "nombre" => "J&#46;"
            "apellidos" => "Ena"
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">s</span>"
                "identificador" => "aff0100"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">d</span>"
                "identificador" => "aff0020"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:20 [
          0 => array:3 [
            "entidad" => "Servicio de Medicina Interna&#44; Hospital Regional Universitario de M&#225;laga&#44; M&#225;laga&#44; Spain"
            "etiqueta" => "a"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "Instituto de Investigaci&#243;n Biom&#233;dica de M&#225;laga &#40;IBIMA&#41;&#44; Spain"
            "etiqueta" => "b"
            "identificador" => "aff0010"
          ]
          2 => array:3 [
            "entidad" => "CIBER de Obesidad y Nutrici&#243;n &#40;CIBEROBN&#41;&#44; Instituto de Salud Carlos III&#44; Spain"
            "etiqueta" => "c"
            "identificador" => "aff0015"
          ]
          3 => array:3 [
            "entidad" => "Sociedad Espa&#241;ola de Medicina Interna &#40;SEMI&#41;&#44; Spain"
            "etiqueta" => "d"
            "identificador" => "aff0020"
          ]
          4 => array:3 [
            "entidad" => "Unidad de Endocrinolog&#237;a y Nutrici&#243;n&#44; Hospital General de Segovia&#44; Segovia&#44; Spain"
            "etiqueta" => "e"
            "identificador" => "aff0025"
          ]
          5 => array:3 [
            "entidad" => "Sociedad Espa&#241;ola de Diabetes &#40;SED&#41;&#44; Spain"
            "etiqueta" => "f"
            "identificador" => "aff0030"
          ]
          6 => array:3 [
            "entidad" => "Servicio de Geriatr&#237;a&#44; Hospital Universitario de Getafe&#44; Madrid&#44; Spain"
            "etiqueta" => "g"
            "identificador" => "aff0035"
          ]
          7 => array:3 [
            "entidad" => "CIBER de Fragilidad y Envejecimiento Saludable &#40;CIBERFES&#41;&#44; Instituto de Salud Carlos III&#44; Spain"
            "etiqueta" => "h"
            "identificador" => "aff0040"
          ]
          8 => array:3 [
            "entidad" => "Sociedad Espa&#241;ola de Medicina Geri&#225;trica &#40;SEMEG&#41;&#44; Spain"
            "etiqueta" => "i"
            "identificador" => "aff0045"
          ]
          9 => array:3 [
            "entidad" => "Unidad de Geriatr&#237;a&#44; Hospital Universitari de Bellvitge&#44; L¿Hospitalet de Llobregat&#44; Barcelona&#44; Spain"
            "etiqueta" => "j"
            "identificador" => "aff0050"
          ]
          10 => array:3 [
            "entidad" => "Sociedad Espa&#241;ola de Geriatr&#237;a y Gerontolog&#237;a &#40;SEGG&#41;&#44; Spain"
            "etiqueta" => "k"
            "identificador" => "aff0055"
          ]
          11 => array:3 [
            "entidad" => "Servicio de Endocrinolog&#237;a y Nutrici&#243;n&#44; Hospital Germans Trias i Pujol&#44; Badalona&#44; Barcelona&#44; Spain"
            "etiqueta" => "l"
            "identificador" => "aff0060"
          ]
          12 => array:3 [
            "entidad" => "Institut d&#8217;Investigaci&#243; en Ci&#232;ncies de la Salut Germans Trias i Pujol&#44; Badalona&#44; Barcelona&#44; Spain"
            "etiqueta" => "m"
            "identificador" => "aff0065"
          ]
          13 => array:3 [
            "entidad" => "CIBER de Diabetes y Enfermedades Metab&#243;licas Asociadas &#40;CIBERDEM&#41;&#44; Instituto de Salud Carlos III&#44; Spain"
            "etiqueta" => "n"
            "identificador" => "aff0070"
          ]
          14 => array:3 [
            "entidad" => "Sociedad Espa&#241;ola de Endocrinolog&#237;a y Nutrici&#243;n &#40;SEEN&#41;&#44; Spain"
            "etiqueta" => "&#241;"
            "identificador" => "aff0075"
          ]
          15 => array:3 [
            "entidad" => "Centro de Salud Burgos Rural&#44; Burgos&#44; Spain"
            "etiqueta" => "o"
            "identificador" => "aff0080"
          ]
          16 => array:3 [
            "entidad" => "Sociedad Espa&#241;ola de Medicina General &#40;SEMERGEN&#41;&#44; Spain"
            "etiqueta" => "p"
            "identificador" => "aff0085"
          ]
          17 => array:3 [
            "entidad" => "Centro de Salud Buenavista&#44; Toledo&#44; Spain"
            "etiqueta" => "q"
            "identificador" => "aff0090"
          ]
          18 => array:3 [
            "entidad" => "Sociedad Espa&#241;ola de M&#233;dicos Generales y de Familia &#40;SEMG&#41;&#44; Spain"
            "etiqueta" => "r"
            "identificador" => "aff0095"
          ]
          19 => array:3 [
            "entidad" => "Servicio de Medicina Interna&#44; Hospital Marina Baixa&#44; La Vila Joiosa&#44; Alicante&#44; Spain"
            "etiqueta" => "s"
            "identificador" => "aff0100"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Corresponding author&#46;"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "Tratamiento de la diabetes mellitus tipo 2 en el paciente anciano"
      ]
    ]
    "resumenGrafico" => array:2 [
      "original" => 0
      "multimedia" => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1519
            "Ancho" => 2506
            "Tamanyo" => 258442
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Treatment algorithm for type 2 diabetes mellitus in elderly patients&#46;</p> <p id="spar0020" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; DPP4i&#58; dipeptidyl peptidase-4 inhibitors&#59; GLP-1RA&#58; glucagon-like peptide-1 receptor agonists&#59; SGLT2i&#58; sodium-glucose cotransporter 2 inhibitors&#46;</p> <p id="spar0025" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">a</span> Repaglinide and pioglitazone can be used in patients with GFR &#60;30<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#44; but their use is not recommended due to the risk of adverse effects&#58; hypoglycemia &#40;repaglinide&#41;&#59; salt and fluid retention&#44; heart failure and fractures &#40;pioglitazone&#41;&#46;</p> <p id="spar0030" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">b</span> Empagliflozin&#44; canagliflozin and liraglutide have shown reduced cardiovascular morbidity and mortality in patients with high vascular risk type 2 diabetes&#46;</p> <p id="spar0035" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">c</span> Saxagliptin should be avoided for patients with heart failure&#46;</p> <p id="spar0040" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">d</span> Pioglitazone is contraindicated for patients with heart failure or at risk for fractures&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Background</span><p id="par0005" class="elsevierStylePara elsevierViewall">Aging is characterized by a progressive loss of an individual&#39;s functional capacity&#46; The elderly population is biologically heterogeneous&#44; thereby necessitating a comprehensive assessment&#44; one that includes functional aspects in the decision-making process&#46;<a class="elsevierStyleCrossRef" href="#bib0930"><span class="elsevierStyleSup">1</span></a> Although there is no consensus on the definition of an individual as elderly&#44; this document uses the operational definition of having an age greater than 75 years or presenting frailty&#46;<a class="elsevierStyleCrossRef" href="#bib0935"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Demographic predictions put Spain as one of the most aged countries in the world&#46; In 2050&#44; 12&#37; of the Spanish population will be 80 years of age or older&#46;<a class="elsevierStyleCrossRef" href="#bib0940"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Type 2 diabetes mellitus &#40;DM2&#41; is a disease closely linked to aging&#44; and its prevalence increases markedly with age&#46; This situation is due to the combination of insulin secretion deficiency&#44; insulin resistance &#40;related to the increase in visceral&#44; intermuscular and intramuscular adiposity&#41;&#44; sarcopenia and physical inactivity in elderly patients&#46; In Spain&#44; 63&#37; of patients with diabetes &#40;of whom more than 90&#37; have DM2&#41; are older than 65 years&#44;<a class="elsevierStyleCrossRef" href="#bib0945"><span class="elsevierStyleSup">4</span></a> and more than a third of the population older than 75 years has diabetes&#46;<a class="elsevierStyleCrossRef" href="#bib0950"><span class="elsevierStyleSup">5</span></a> It has been predicted that the number of patients with diabetes older than 70 years will quadruple worldwide in the next 3 decades due to the increase in DM2&#46;<a class="elsevierStyleCrossRef" href="#bib0955"><span class="elsevierStyleSup">6</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Antidiabetic treatment and the objectives of glycemic control in elderly patients with DM2 should be individualized according to their biopsychosocial characteristics&#46; In elderly patients for whom the benefits of intensive antidiabetic treatment are limited&#44; the basic objectives should be to improve the quality of life&#44; preserve functionality and prevent adverse effects&#44; especially hypoglycemia&#46;<a class="elsevierStyleCrossRef" href="#bib0960"><span class="elsevierStyleSup">7</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Treatment of DM2 in the elderly was the subject of a consensus document published in 2012 and endorsed by several Spanish scientific societies&#46;<a class="elsevierStyleCrossRef" href="#bib0965"><span class="elsevierStyleSup">8</span></a> Since then&#44; new therapeutic groups and evidence have emerged that warrant an update to this consensus document&#46; The present document focuses on the therapeutic aspects of DM2 in elderly patients&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Functional capacity&#44; frailty and diabetes</span><p id="par0030" class="elsevierStylePara elsevierViewall">Frailty is a clinical syndrome associated with aging&#44; characterized by the presence of at least 3 of the following criteria&#58; involuntary weight loss&#44; exhaustion&#44; muscle weakness&#44; slowness of gait and physical hypoactivity &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0935"><span class="elsevierStyleSup">2</span></a> Frailty is the main predictor of disability&#44; dependence and mortality in the elderly&#44;<a class="elsevierStyleCrossRef" href="#bib0970"><span class="elsevierStyleSup">9</span></a> including those with diabetes&#44;<a class="elsevierStyleCrossRef" href="#bib0975"><span class="elsevierStyleSup">10</span></a> and is a more potent prognostic marker than the comorbidity burden&#46;<a class="elsevierStyleCrossRef" href="#bib0980"><span class="elsevierStyleSup">11</span></a> Diabetes is a risk factor for the development of frailty&#44;<a class="elsevierStyleCrossRef" href="#bib0985"><span class="elsevierStyleSup">12</span></a> both for predisposing patients to sarcopenia and cognitive dysfunction and for microvascular and macrovascular complications &#40;retinopathy&#44; polyneuropathy&#44; dysautonomia&#44; renal failure and cardiovascular disease&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0930"><span class="elsevierStyleSup">1</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">Early detection of frailty and sarcopenia are key aspects in the management of elderly patients in general<a class="elsevierStyleCrossRefs" href="#bib0990"><span class="elsevierStyleSup">13&#44;14</span></a> and in those who have diabetes in particular&#46;<a class="elsevierStyleCrossRef" href="#bib0930"><span class="elsevierStyleSup">1</span></a> The objectives of glycemic control should be based on the patient&#39;s functional status&#44; because neither frail elderly patients nor those with established functional impairment will benefit from strict glycemic control&#44;<a class="elsevierStyleCrossRef" href="#bib1000"><span class="elsevierStyleSup">15</span></a> which can simultaneously increase the risk of hypoglycemia&#46;<a class="elsevierStyleCrossRef" href="#bib1005"><span class="elsevierStyleSup">16</span></a> A recent study concluded that the degree of glycemic control in institutionalized elderly patients was not related to persistent functional impairment or death&#44; which highlighted the need to be conservative when managing diabetes in this population&#46;<a class="elsevierStyleCrossRef" href="#bib1010"><span class="elsevierStyleSup">17</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The early implementation of multimodal and multidisciplinary interventions in elderly patients with DM2&#44; based on nutritional education and promoting physical activity&#44; has been shown effective for maintaining functional autonomy&#46;<a class="elsevierStyleCrossRef" href="#bib1015"><span class="elsevierStyleSup">18</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Hypoglycemia in elderly patients</span><p id="par0045" class="elsevierStylePara elsevierViewall">The risk of severe hypoglycemia increases exponentially with age&#46; A recent epidemiological study&#44; performed on a Spanish population&#44; reported that more than two-thirds of cases of severe hypoglycemia treated in emergency departments occurred in individuals older than 60 years&#44; and 46&#37; occurred in those older than 76 years&#46;<a class="elsevierStyleCrossRef" href="#bib1020"><span class="elsevierStyleSup">19</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">In Spain&#44; the mean age of patients with diabetes hospitalized for severe hypoglycemia exceeded 70 years&#46;<a class="elsevierStyleCrossRef" href="#bib1025"><span class="elsevierStyleSup">20</span></a> Even so&#44; overtreatment of hyperglycemia remains the rule&#44; as demonstrated by published data from the United States<a class="elsevierStyleCrossRef" href="#bib1030"><span class="elsevierStyleSup">21</span></a> and Spain&#46;<a class="elsevierStyleCrossRef" href="#bib1035"><span class="elsevierStyleSup">22</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Elderly patients are more exposed to polypharmacy&#44; drug interactions and adverse drug effects&#46; Hypoglycemia secondary to the use of antidiabetic agents &#40;insulin&#44; sulfonylureas&#41; represents the second leading cause of hospitalization in emergency departments due to adverse drug effects&#46;<a class="elsevierStyleCrossRef" href="#bib1040"><span class="elsevierStyleSup">23</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">The higher rate of severe hypoglycemia is partly explained by the fact that&#44; due to the lack of adrenergic alarm symptoms&#44; asymptomatic hypoglycemia is more common in the elderly&#44;<a class="elsevierStyleCrossRef" href="#bib1045"><span class="elsevierStyleSup">24</span></a> even in those who have poor glycemic control&#46;<a class="elsevierStyleCrossRef" href="#bib1050"><span class="elsevierStyleSup">25</span></a> Elderly patients with cognitive disorder are a special risk group for severe hypoglycemia&#46;<a class="elsevierStyleCrossRef" href="#bib1055"><span class="elsevierStyleSup">26</span></a> Hypoglycemia in the elderly is associated with delirium&#44; cognitive impairment&#44; falls and fractures&#44; stroke&#44; cardiac arrhythmia and increased mortality&#46;<a class="elsevierStyleCrossRefs" href="#bib1060"><span class="elsevierStyleSup">27&#8211;29</span></a> Preventing hypoglycemia should therefore be a therapeutic priority&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">As a general rule for elderly patients&#44; it is recommended that treatment be started with antidiabetic agents with low hypoglycemic risk &#40;especially metformin and dipeptidyl peptidase-4 inhibitors &#91;DPP-4i&#93;&#41; at low doses&#44; with a progressive increase in dose&#44; monitoring the response after each increase&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1075"><span class="elsevierStyleSup">30</span></a> As much as possible&#44; drugs associated with a high risk of hypoglycemia &#40;sulfonylureas and insulin&#44; especially prandial and mixtures&#41; should be avoided&#46;<a class="elsevierStyleCrossRef" href="#bib0965"><span class="elsevierStyleSup">8</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">General principles in the treatment of elderly patients with type 2 diabetes</span><p id="par0070" class="elsevierStylePara elsevierViewall">The general principles that should govern the treatment of elderly patients with DM2 are as follows&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1&#46;</span><p id="par0075" class="elsevierStylePara elsevierViewall">The therapeutic plan and glycemic control objectives should be based on a comprehensive patient assessment that accounts for the comorbidities&#44; functional and cognitive capacity&#44; affective disorders &#40;with special emphasis on depressive conditions&#41; and social support&#44; which together help estimate the patient&#39;s total and active life expectancy&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2&#46;</span><p id="par0080" class="elsevierStylePara elsevierViewall">It is essential to establish a shared decision-making process with the patient and their caregiver&#40;s&#41; that includes their wishes&#44; expectations&#44; preferences and capabilities&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">3&#46;</span><p id="par0085" class="elsevierStylePara elsevierViewall">The antidiabetic treatment objectives should be to preserve functional capacity and improve the quality of life&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">4&#46;</span><p id="par0090" class="elsevierStylePara elsevierViewall">Special attention should be paid to the contraindications&#44; adverse effects and potential drug interactions of antidiabetic drugs&#46;</p></li></ul></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Glycemic control objectives for elderly patients</span><p id="par0095" class="elsevierStylePara elsevierViewall">The glycemic control objectives for elderly patients should be adapted to the patients&#8217; functional and cognitive status&#44; comorbidities and life expectancy&#46;<a class="elsevierStyleCrossRef" href="#bib0965"><span class="elsevierStyleSup">8</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">Based on the individual assessment&#44; 3 possibilities should be considered&#58; 1&#41; healthy elderly individuals with good functional and cognitive status&#44; low comorbidity burden and good life expectancy&#58; the therapeutic interventions and objectives may be similar to those of young adults with diabetes &#40;HbA1c&#44; 7&#8211;7&#46;5&#37;&#41;<a class="elsevierStyleCrossRef" href="#bib1080"><span class="elsevierStyleSup">31</span></a>&#59; 2&#41; frail elderly with functional disability&#44; dementia and&#47;or limited life expectancy&#58; Symptomatic hypoglycemia and hyperglycemia should be prevented&#46; A reasonable objective would be to maintain an HbA1c level of 7&#46;5&#8211;8&#46;5&#37;<a class="elsevierStyleCrossRefs" href="#bib0965"><span class="elsevierStyleSup">8&#44;32</span></a>&#59; and 3&#41; elderly patients undergoing palliative care&#58; The priority should be to preserve the quality of life&#44; prevent symptomatic hyperglycemia and hypoglycemia and reduce the burden associated with antidiabetic treatment&#46; In this context&#44; measuring HbA1c is not relevant&#46; Blood sugar should be kept below the renal threshold for glucose &#40;&#60;200<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#41;&#46; The treatment should be simplified&#44; avoiding drugs that induce hypoglycemia and those associated with gastrointestinal symptoms and hyporexia&#46; Prandial insulin can be discontinued or substituted by oral drugs&#46; The number of capillary blood sugar checks should be decreased or even eliminated&#46;<a class="elsevierStyleCrossRef" href="#bib1090"><span class="elsevierStyleSup">33</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Nonpharmacological treatment&#58; nutrition and physical activity</span><p id="par0105" class="elsevierStylePara elsevierViewall">There is little evidence of the benefits of lifestyle changes &#40;therapeutic education&#44; nutrition counseling&#44; individualized physical activity&#41; for elderly or frail patients with DM2&#46;<a class="elsevierStyleCrossRef" href="#bib1080"><span class="elsevierStyleSup">31</span></a> A study is currently underway to analyze the impact of lifestyle changes on the functional capacity and quality of life of frail and &#8220;prefrail&#8221; elderly patients with DM2&#46;<a class="elsevierStyleCrossRef" href="#bib1095"><span class="elsevierStyleSup">34</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">The Look AHEAD study included patients younger than 75 years &#40;mean age&#44; 59 years&#41; with DM2 and obesity and found that although an intensive multifactorial intervention aimed at weight loss did not manage to reduce cardiovascular events&#44;<a class="elsevierStyleCrossRef" href="#bib1100"><span class="elsevierStyleSup">35</span></a> it did improve the achievement of the objectives of metabolic control&#44; cardiovascular risk factors&#44; functional status and quality of life&#46;<a class="elsevierStyleCrossRef" href="#bib1105"><span class="elsevierStyleSup">36</span></a> This benefit was greater in the older subgroup &#40;65&#8211;75 years&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1110"><span class="elsevierStyleSup">37</span></a> Nutrition education programs have shown improved metabolic control in the elderly&#46;<a class="elsevierStyleCrossRef" href="#bib1115"><span class="elsevierStyleSup">38</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Excessively low-calorie diets should be avoided in elderly patients due to increased risk of hypoglycemia and malnutrition&#44; as these diets typically provide few proteins&#46; This fact is important because sarcopenic obesity is frequent in the elderly and is characterized by a high body mass index &#40;BMI&#41; and low muscle mass&#46; Highly restrictive diets can therefore worsen sarcopenia&#44; which is associated with functional impairment&#44; a risk of falls and institutionalization&#46;<a class="elsevierStyleCrossRefs" href="#bib1120"><span class="elsevierStyleSup">39&#44;40</span></a> Elderly patients might also need calcium and vitamin D and B12 supplements&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">The elderly are often believed not to benefit from variable-intensity physical exercise programs&#44; not being able to perform them or not having good adherence&#46; However&#44; physical activity&#44; especially multicomponent activity &#40;aerobic&#44; resistance&#44; flexibility and balance&#41;&#44; has shown its efficacy in the elderly with diabetes&#44; improving not only glycemic control but also functional independence&#44; self-esteem and quality of life&#46; Its practice should therefore be recommended&#46;<a class="elsevierStyleCrossRef" href="#bib1130"><span class="elsevierStyleSup">41</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">The prescription of physical activity should be adapted to the patient&#39;s limitations and preferences&#46; Before implementing a physical activity program&#44; the presence of potential contraindications&#44; geriatric syndromes and limitations resulting from drug treatment should be ruled out&#46; When starting a program&#44; it is important to prevent orthostatic hypotension&#44; dehydration and hypoglycemia &#40;especially in patients treated with insulin or secretagogues&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1130"><span class="elsevierStyleSup">41</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">Aerobic activities should be preferably indicated&#44; although they are often limited by the associated comorbidity &#40;e&#46;g&#46;&#44; cardiovascular and muscle-skeletal diseases&#41;&#46; Aerobic exercises prevent falls&#44; sarcopenia and functional impairment in patients with diabetes<a class="elsevierStyleCrossRef" href="#bib1135"><span class="elsevierStyleSup">42</span></a> and improves the cardiovascular risk profile&#46;<a class="elsevierStyleCrossRef" href="#bib1140"><span class="elsevierStyleSup">43</span></a> Even a simple program of regular strolls decreases glycemia under fasting conditions&#44; HbA1c and triglyceride levels in elderly patients with DM2&#46;<a class="elsevierStyleCrossRef" href="#bib1145"><span class="elsevierStyleSup">44</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">Resistance training to increase muscle mass is considered an essential component for preventing and treating DM2 in the elderly and is the program of choice for frail elderly patients&#46; Moderate to high-intensity exercises are&#44; in contrast to previous assumptions&#44; more effective for glycemic control and are generally safe for the elderly population&#46; Exercises reaching 60&#8211;70&#37; of the maximum load are usually considered sufficient &#40;in weight training&#44; the maximum weight that can be lifted in a certain exercise to perform one repetition is called a one-repetition maximum&#41;&#46; Resistance training has shown metabolic benefits in elderly patients with DM2 &#40;improved insulin sensitivity&#44; reduced blood glucose under fasting conditions and reduced visceral adiposity&#41;<a class="elsevierStyleCrossRef" href="#bib1150"><span class="elsevierStyleSup">45</span></a> and is associated with improved muscle strength and mobility and reduced falls&#46;<a class="elsevierStyleCrossRef" href="#bib1155"><span class="elsevierStyleSup">46</span></a> However&#44; to maintain the benefits of resistance training&#44; continuous supervision is usually required&#46;<a class="elsevierStyleCrossRef" href="#bib1160"><span class="elsevierStyleSup">47</span></a> Lastly&#44; balance training reduces falls in the elderly with DM2&#46;<a class="elsevierStyleCrossRef" href="#bib1165"><span class="elsevierStyleSup">48</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Pharmacotherapy</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Metformin</span><p id="par0140" class="elsevierStylePara elsevierViewall">Although no specific clinical trials have evaluated the safety and efficacy of metformin in the elderly&#44; clinical experience supports its use as the basis of DM2 therapy in any age group&#44;<a class="elsevierStyleCrossRefs" href="#bib1170"><span class="elsevierStyleSup">49&#8211;51</span></a> especially for patients with a high BMI&#44;<a class="elsevierStyleCrossRef" href="#bib1185"><span class="elsevierStyleSup">52</span></a> although it is also effective in those with normal weight&#46; Metformin acts through numerous mechanisms&#44; although the main mechanism appears to be the activation of adenosine monophosphate-kinase&#44; which leads to a reduction in the release of glucose by the liver&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Metformin does not usually cause hypoglycemia and has been shown to be useful in patients with cardiovascular disease or stable heart failure&#46;<a class="elsevierStyleCrossRef" href="#bib1190"><span class="elsevierStyleSup">53</span></a> Nevertheless&#44; the use of metformin in the elderly can be associated with adverse events such as gastrointestinal intolerance&#44; dysgeusia&#44; hyporexia and vitamin B12 deficiency&#44;<a class="elsevierStyleCrossRef" href="#bib1195"><span class="elsevierStyleSup">54</span></a> the latter of which should be periodically monitored&#46;<a class="elsevierStyleCrossRef" href="#bib1200"><span class="elsevierStyleSup">55</span></a> Metformin is contraindicated for patients with glomerular filtration rates &#60;30<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#46;<a class="elsevierStyleCrossRefs" href="#bib1205"><span class="elsevierStyleSup">56&#44;57</span></a> Although lactic acidosis is uncommon&#44; half of patients older than 65 years present undiagnosed renal function&#46;<a class="elsevierStyleCrossRef" href="#bib1215"><span class="elsevierStyleSup">58</span></a> It is therefore important to periodically monitor the renal function and reduce the dosage if the glomerular filtration rate is &#60;45<span class="elsevierStyleHsp" style=""></span>mL&#47;min or discontinue it if &#60;30<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#46;<a class="elsevierStyleCrossRefs" href="#bib1220"><span class="elsevierStyleSup">59&#44;60</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">The use of metformin should be avoided in conditions of tissue hypoxia&#44; respiratory failure&#44; acute heart failure&#44; hepatic impairment and when there is acute intercurrent disease&#44; when iodinated contrast media is administered or when there is a risk of functional renal failure &#40;vomiting&#44; diarrhea&#41;&#46; The usefulness of metformin is highly limited in patients with anorexia and low weight&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Treatment should be started with a progressive titration from 425<span class="elsevierStyleHsp" style=""></span>mg&#47;day &#40;half of an 850-mg tablet&#41; to 1700<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#46; Higher dosages are not recommended because they increase the adverse effects without improving the efficacy&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Five percent of patients have to discontinue using the drug due to poor gastrointestinal tolerance&#44; a rate that can be higher in elderly patients&#46;<a class="elsevierStyleCrossRef" href="#bib1230"><span class="elsevierStyleSup">61</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Sulfonylureas</span><p id="par0165" class="elsevierStylePara elsevierViewall">These are low-cost and widely used drugs&#46; They reduce the microvascular complications of DM2<a class="elsevierStyleCrossRef" href="#bib1235"><span class="elsevierStyleSup">62</span></a> and increase the release of insulin by blocking the adenosine triphosphate-sensitive potassium channels in pancreatic beta cells&#46; Sulfonylureas should be used with caution given that the risk of severe hypoglycemia increases exponentially with age&#44; especially with glibenclamide&#44;<a class="elsevierStyleCrossRef" href="#bib1240"><span class="elsevierStyleSup">63</span></a> which is contraindicated for elderly patients&#44;<a class="elsevierStyleCrossRef" href="#bib1245"><span class="elsevierStyleSup">64</span></a> with glimepiride<a class="elsevierStyleCrossRef" href="#bib1250"><span class="elsevierStyleSup">65</span></a> or especially gliclazide being preferable&#44;<a class="elsevierStyleCrossRef" href="#bib1255"><span class="elsevierStyleSup">66</span></a> which produces the least hypoglycemia&#46;<a class="elsevierStyleCrossRefs" href="#bib1260"><span class="elsevierStyleSup">67&#44;68</span></a> Sulfonylureas also induce weight gain and are not recommended for patients with renal failure or high cardiovascular risk&#46; Hypoglycemia is boosted in the presence of renal or hepatic failure&#44; the concomitant administration of other oral diabetes drugs or insulin&#44; a recent hospital discharge&#44; advanced age&#44; reduced dietary intake and the use of 5 or more drugs&#46;<a class="elsevierStyleCrossRef" href="#bib1270"><span class="elsevierStyleSup">69</span></a> Sulfonylureas have multiple drug interactions &#40;salicylates&#44; dicoumarin agents&#44; sulfonamides&#44; &#64257;brates&#44; allopurinol&#44; methotrexate&#44; diuretics&#44; beta-blockers&#44; corticosteroids&#41;&#44; which complicate their use in polymedicated patients&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Meglitinides &#40;repaglinide&#44; nateglinide&#41;</span><p id="par0170" class="elsevierStylePara elsevierViewall">These are secretagogues&#44; as are sulfonylureas&#44; but with faster and shorter action and a higher cost&#46; They act preferentially on postprandial hyperglycemia&#46; Their more limited pharmacokinetic profile reduces the risk of hypoglycemia compared with sulfonylureas&#44;<a class="elsevierStyleCrossRef" href="#bib1275"><span class="elsevierStyleSup">70</span></a> especially in elderly patients with erratic eating patterns&#46;<a class="elsevierStyleCrossRef" href="#bib1280"><span class="elsevierStyleSup">71</span></a> Repaglinide&#44; due to its mainly biliary elimination&#44; can be used for patients with moderate to advanced renal failure&#46;<a class="elsevierStyleCrossRef" href="#bib1285"><span class="elsevierStyleSup">72</span></a> Combining the drug with gemfibrozil<a class="elsevierStyleCrossRef" href="#bib1290"><span class="elsevierStyleSup">73</span></a> or other drugs that activate or inhibit cytochrome P450 is contraindicated&#46; The drug should be administered approximately 15<span class="elsevierStyleHsp" style=""></span>min before meals&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Alpha-glucosidase inhibitors &#40;acarbose&#44; miglitol&#41;</span><p id="par0175" class="elsevierStylePara elsevierViewall">These drugs inhibit intestinal alpha-glucosidase&#44; slowing digestion and intestinal absorption of carbohydrates&#46; These inhibitors are especially aimed at controlling postprandial glycemia&#44; especially in patients who have carbohydrate-rich diets&#46; The drugs have systemic effects and can reduce the risk of cardiovascular events and arterial hypertension&#46;<a class="elsevierStyleCrossRef" href="#bib1295"><span class="elsevierStyleSup">74</span></a> Although the drugs do not induce hypoglycemia and can be potentially useful for some elderly patients with diabetes&#44;<a class="elsevierStyleCrossRefs" href="#bib1300"><span class="elsevierStyleSup">75&#44;76</span></a> their use can be limited by their low efficacy and high rate of adverse gastrointestinal effects &#40;flatulence&#44; diarrhea&#41;&#44; both in monotherapy and especially in combination with metformin&#46; These inhibitors can change digoxin and acenocoumarol levels&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Thiazolidinediones &#40;pioglitazone&#41;</span><p id="par0180" class="elsevierStylePara elsevierViewall">These agents act by increasing peripheral insulin sensitivity&#46; Thiazolidinediones provide longer-lasting glycemic control than metformin and sulfonylureas&#46;<a class="elsevierStyleCrossRef" href="#bib1310"><span class="elsevierStyleSup">77</span></a> Pioglitazone does not produce hypoglycemia and acts favorably on the lipid profile &#40;increased HDL-cholesterol and reduced triglyceride levels&#41;&#46; Pioglitazone can be beneficial in the secondary prevention of cardiovascular events &#40;proACTIVE study&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib1315"><span class="elsevierStyleSup">78</span></a> with reduced all-cause mortality&#46;<a class="elsevierStyleCrossRef" href="#bib1320"><span class="elsevierStyleSup">79</span></a> The drug has also been shown to histologically improve nonalcoholic steatohepatitis in patients with prediabetes or DM2&#46;<a class="elsevierStyleCrossRef" href="#bib1325"><span class="elsevierStyleSup">80</span></a> However&#44; pioglitazone has various adverse effects that limit its use in the elderly&#44;<a class="elsevierStyleCrossRefs" href="#bib1330"><span class="elsevierStyleSup">81&#44;82</span></a> such as weight gain&#44; salt and fluid retention&#44; dilutional anemia&#44; increased risk of heart failure&#44;<a class="elsevierStyleCrossRef" href="#bib1340"><span class="elsevierStyleSup">83</span></a> increased risk of fractures &#40;especially in postmenopausal women&#41;<a class="elsevierStyleCrossRef" href="#bib1345"><span class="elsevierStyleSup">84</span></a> and the possibility of accelerating cognitive impairment&#46;<a class="elsevierStyleCrossRef" href="#bib1350"><span class="elsevierStyleSup">85</span></a> The increased risk of bladder cancer with the long-term use of pioglitazone is a subject of debate&#46;<a class="elsevierStyleCrossRefs" href="#bib1355"><span class="elsevierStyleSup">86&#44;87</span></a></p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Dipeptidyl peptidase-4 inhibitors &#40;sitagliptin&#44; vildagliptin&#44; saxagliptin&#44; linagliptin&#44; alogliptin&#41;</span><p id="par0185" class="elsevierStylePara elsevierViewall">These drugs act by inhibiting the proteolytic dipeptidyl peptidase-4 &#40;DPP-4&#41; enzyme&#44; which degrades the incretin hormones&#44; increasing the availability and action of endogenous glucagon-like peptide-1 &#40;GLP-1&#41;&#46; DPP4i have been shown to be useful in monotherapy&#44; in combination with other hypoglycemic agents and in triple therapy&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">These oral drugs are well tolerated&#44; effective and safe in the short<a class="elsevierStyleCrossRefs" href="#bib1365"><span class="elsevierStyleSup">88&#44;89</span></a> and long term&#44;<a class="elsevierStyleCrossRefs" href="#bib1375"><span class="elsevierStyleSup">90&#44;91</span></a> in elderly and young patients with diabetes&#46;<a class="elsevierStyleCrossRef" href="#bib1385"><span class="elsevierStyleSup">92</span></a> The drugs have no effect on gastric emptying&#44; do not induce reduced central intake and do not cause gastrointestinal intolerance or weight loss&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">DPP4i do not induce hypoglycemia &#40;glucose-dependent mechanism&#41;&#44; do not change body weight and have no significant drug interactions&#44; which makes them an attractive therapeutic option for treating DM2 in the elderly&#46; These inhibitors do not require dose adjustments in elderly patients&#46; Several studies have shown the safety and efficacy of vildagliptin&#44;<a class="elsevierStyleCrossRefs" href="#bib1390"><span class="elsevierStyleSup">93&#8211;95</span></a> sitagliptin&#44;<a class="elsevierStyleCrossRefs" href="#bib1405"><span class="elsevierStyleSup">96&#44;97</span></a> saxagliptin&#44;<a class="elsevierStyleCrossRefs" href="#bib1405"><span class="elsevierStyleSup">96&#8211;101</span></a> linagliptin<a class="elsevierStyleCrossRefs" href="#bib1435"><span class="elsevierStyleSup">102&#8211;104</span></a> and alogliptin<a class="elsevierStyleCrossRef" href="#bib1450"><span class="elsevierStyleSup">105</span></a> in elderly patients&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">DPP4i have shown their cardiovascular safety in clinical trials performed on patients with high cardiovascular risk&#44;<a class="elsevierStyleCrossRefs" href="#bib1455"><span class="elsevierStyleSup">106&#8211;108</span></a> including patients older than 75 years&#46;<a class="elsevierStyleCrossRef" href="#bib1470"><span class="elsevierStyleSup">109</span></a> In the SAVOR-TIMI 53 study&#44;<a class="elsevierStyleCrossRef" href="#bib1455"><span class="elsevierStyleSup">106</span></a> the use of saxagliptin was associated with a significant increase in hospitalizations for heart failure&#44; especially among patients with high baseline levels of B-type natriuretic peptide &#40;BNP&#41; or with a prior history of heart failure or chronic renal failure&#46;<a class="elsevierStyleCrossRefs" href="#bib1475"><span class="elsevierStyleSup">110&#44;111</span></a> The EXAMINE study<a class="elsevierStyleCrossRef" href="#bib1460"><span class="elsevierStyleSup">107</span></a> also observed a greater tendency &#40;although not significant&#41; to develop heart failure among patients treated with alogliptin&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">However&#44; extensive observational studies in standard clinical practice<a class="elsevierStyleCrossRef" href="#bib1485"><span class="elsevierStyleSup">112</span></a> and the TECOS study with sitagliptin<a class="elsevierStyleCrossRef" href="#bib1490"><span class="elsevierStyleSup">113</span></a> could not confirm an association between these drugs and an increased rate of heart failure&#46; Furthermore&#44; separate meta-analyses of patients with DM2 treated with vildagliptin<a class="elsevierStyleCrossRef" href="#bib1495"><span class="elsevierStyleSup">114</span></a> or linagliptin<a class="elsevierStyleCrossRef" href="#bib1500"><span class="elsevierStyleSup">115</span></a> support its cardiovascular safety and the absence of heart failure risk&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">Vildagliptin is the only DPP4i that has had a clinical trial with patients with DM2 and chronic heart failure &#40;NYHA functional class <span class="elsevierStyleSmallCaps">I&#8211;III</span>&#41; with a left ventricular ejection fraction &#60;40&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib1505"><span class="elsevierStyleSup">116</span></a> Treatment with vildagliptin&#44; compared with placebo&#44; was not associated with significant changes in the latter&#44; thereby meeting the objective of noninferiority&#46;<a class="elsevierStyleCrossRef" href="#bib1505"><span class="elsevierStyleSup">116</span></a></p><p id="par0215" class="elsevierStylePara elsevierViewall">DPP4i can be used safely&#44; without the risk of hypoglycemia&#44; at any stage of chronic renal failure&#46; All of these inhibitors require dose adjustments in cases of moderate to severe renal failure&#44; except for linagliptin&#44; which is eliminated by the bile duct&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">DPP4i have few drug interactions&#44; an important advantage for elderly patients&#44; for whom polypharmacy is common&#46;<a class="elsevierStyleCrossRef" href="#bib1510"><span class="elsevierStyleSup">117</span></a> Vildagliptin is not metabolized by cytochrome P450 and therefore has a lower risk of interactions&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Glucagon-like peptide-1 receptor agonists &#40;exenatide&#44; liraglutide&#44; lixisenatide&#44; exenatide-LAR&#44; dulaglutide&#41;</span><p id="par0225" class="elsevierStylePara elsevierViewall">GLP-1 receptor agonists &#40;GLP-1 RA&#41; act by activating GLP-1 receptors&#44; which results in increased insulin secretion and reduced glucagon secretion&#44; depending on the blood glucose level&#46; The agonists also slow gastric emptying and increase the feeling of central satiety&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">These drugs induce significant weight loss and are therefore an option when weight loss is a priority &#40;e&#46;g&#46;&#44; elderly with advanced gonarthrosis&#44; sleep apnea syndrome&#44; hypoventilation&#44; steatohepatitis and metabolic syndrome&#41;&#46; However&#44; weight loss and reduced appetite can have undesirable effects in frail elderly patients&#44; for whom hyporexia and malnutrition are common&#46; The presence of sarcopenic obesity is common among elderly patients &#40;excess adiposity with little lean mass due to loss of muscle mass&#41;&#46; Sarcopenia is a marker of a poor functional and vital prognosis&#46; Weight loss &#40;a desirable objective in most patients with DM2&#41; at the cost of lean mass can therefore be counterproductive&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">GLP-1 RAs do not induce hypoglycemia but are associated with frequent gastrointestinal discomfort &#40;nausea&#44; vomiting and diarrhea&#41;&#46; In addition to their high cost&#44; the agonists require subcutaneous administration &#40;daily in 2 doses in the case of exenatide&#59; daily in 1 dose for liraglutide and lixisenatide&#59; and weekly with exenatide-LAR and dulaglutide&#41;&#46; We should therefore ensure that the patient or caregiver have an appropriate level of dexterity before prescribing these drugs&#46; Although there is controversy on the possible onset of pancreatitis with the use of GLP-1 RAs&#44; various studies have not confirmed this association&#44; considering that the higher incidence of pancreatitis is the result of having diabetes&#46;<a class="elsevierStyleCrossRef" href="#bib1515"><span class="elsevierStyleSup">118</span></a></p><p id="par0240" class="elsevierStylePara elsevierViewall">GLP-1 RAs have shown a good cardiovascular safety profile in patients with DM2 of high vascular risk&#46; Compared with placebo&#44; lixisenatide<a class="elsevierStyleCrossRef" href="#bib1520"><span class="elsevierStyleSup">119</span></a> and exenatide LAR<a class="elsevierStyleCrossRef" href="#bib1525"><span class="elsevierStyleSup">120</span></a> have shown noninferiority&#44; while liraglutide<a class="elsevierStyleCrossRef" href="#bib1530"><span class="elsevierStyleSup">121</span></a> and semaglutide &#40;an unmarketed GLP-1 RA that is administered weekly&#41;<a class="elsevierStyleCrossRef" href="#bib1535"><span class="elsevierStyleSup">122</span></a> showed a reduction in cardiovascular events&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">There have been no specific studies with GLP-1 RA in elderly individuals&#46; All analyses by subgroups in patients 65 years of age or older achieved a greater reduction in HbA1c&#44; fewer hypoglycemic events and greater weight loss&#44; although with more gastrointestinal effects than the comparator &#40;glimepiride&#44;<a class="elsevierStyleCrossRef" href="#bib1540"><span class="elsevierStyleSup">123</span></a> sitagliptin&#44;<a class="elsevierStyleCrossRefs" href="#bib1545"><span class="elsevierStyleSup">124&#44;125</span></a> insulin glargine<a class="elsevierStyleCrossRefs" href="#bib1555"><span class="elsevierStyleSup">126&#8211;128</span></a> or placebo&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1570"><span class="elsevierStyleSup">129</span></a> Significant differences have not been observed in terms of safety and efficacy compared with younger patients&#46;<a class="elsevierStyleCrossRef" href="#bib1575"><span class="elsevierStyleSup">130</span></a> In a meta-analysis with lixisenatide<a class="elsevierStyleCrossRef" href="#bib1570"><span class="elsevierStyleSup">129</span></a> and in a grouped analysis with liraglutide&#44;<a class="elsevierStyleCrossRef" href="#bib1575"><span class="elsevierStyleSup">130</span></a> the results for patients older than 65 years were similar to those observed in other age groups&#46; Nevertheless&#44; none of these studies included vulnerable or frail elderly individuals&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall">In conclusion&#44; GLP-1 RAs can be used with caution in elderly patients&#44; customizing their indication &#40;e&#46;g&#46;&#44; elderly patients with obesity and good functional status&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1580"><span class="elsevierStyleSup">131</span></a> These drugs should not be administered to frail elderly patients<a class="elsevierStyleCrossRef" href="#bib1075"><span class="elsevierStyleSup">30</span></a> or those with a history of pancreatitis and&#47;or glomerular filtration rates &#60;30<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#46;<a class="elsevierStyleCrossRef" href="#bib1585"><span class="elsevierStyleSup">132</span></a></p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Sodium-glucose cotransporter 2 inhibitors &#40;dapagliflozin&#44; canagliflozin&#44; empagliflozin&#41;</span><p id="par0255" class="elsevierStylePara elsevierViewall">These drugs inhibit the sodium-glucose cotransporter 2 &#40;SGLT2&#41; in the renal tubule&#44; preventing the reabsorption of glucose and inducing glycosuria&#46; Given that their mechanism of action is independent of insulin&#44;<a class="elsevierStyleCrossRef" href="#bib1590"><span class="elsevierStyleSup">133</span></a> SGLT2 inhibitors are effective in all stages of DM2 and do not produce hypoglycemia&#46; Due to their glycosuric effect&#44; SGLT2 inhibitors induce a mean weight loss of 1&#46;8&#8211;2<span class="elsevierStyleHsp" style=""></span>kg&#44; at the expense especially of fat mass&#44; and have a hypotensive effect that causes a mean reduction in systolic blood pressure of &#8722;4&#46;45<span class="elsevierStyleHsp" style=""></span>mmHg&#46;<a class="elsevierStyleCrossRefs" href="#bib1595"><span class="elsevierStyleSup">134&#44;135</span></a> Glycosuria causes osmotic diuresis and polyuria&#46;</p><p id="par0260" class="elsevierStylePara elsevierViewall">These are effective drugs that have shown superiority in glycemic control against sulfonylureas<a class="elsevierStyleCrossRefs" href="#bib1605"><span class="elsevierStyleSup">136&#44;137</span></a> and sitagliptin&#46;<a class="elsevierStyleCrossRef" href="#bib1615"><span class="elsevierStyleSup">138</span></a> The expected reduction in HbA1c levels varies between 0&#46;7&#37; and 1&#37;&#44; sustained up to 3 years of follow-up&#46;</p><p id="par0265" class="elsevierStylePara elsevierViewall">SGLT2 inhibitors are administered in a single daily dose orally&#44; are effective in monotherapy<a class="elsevierStyleCrossRef" href="#bib1620"><span class="elsevierStyleSup">139</span></a> &#40;if there is a contraindication or intolerance to metformin&#41;&#44; as a second hypoglycemic agent and in triple therapy&#46; Hypoglycemia can occur when combining these inhibitors with sulfonylureas or insulin&#46; Therefore&#44; the dosage needs to be reduced or the discontinuation of the sulfonylureas needs to be assessed&#46;<a class="elsevierStyleCrossRef" href="#bib1625"><span class="elsevierStyleSup">140</span></a></p><p id="par0270" class="elsevierStylePara elsevierViewall">In the EMPA-REG study&#44; performed on patients with DM2&#44; cardiovascular disease and a glomerular filtration rate &#62;30<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#46;72<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#44; empagliflozin decreased overall mortality by 32&#37;&#44; hospitalizations for heart failure by 35&#37; and mortality due to cardiovascular causes by 38&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib1630"><span class="elsevierStyleSup">141</span></a> In this study&#44; empagliflozin showed a nephroprotective effect&#44; delaying the progression of renal failure and the need for dialysis&#46;<a class="elsevierStyleCrossRef" href="#bib1635"><span class="elsevierStyleSup">142</span></a> Based on these results&#44; the latest guidelines from the European Society of Cardiology recommend considering the use of the SGLT2 inhibitor empagliflozin in patients with heart failure and DM2&#46;<a class="elsevierStyleCrossRef" href="#bib1640"><span class="elsevierStyleSup">143</span></a></p><p id="par0275" class="elsevierStylePara elsevierViewall">More recently&#44; the results of the study on equivalent cardiovascular safety with canagliflozin have been published&#46;<a class="elsevierStyleCrossRef" href="#bib1645"><span class="elsevierStyleSup">144</span></a> This study involved a grouped analysis of the CANVAS and CANVAS-R studies&#44; which included 10&#44;142 patients with DM2 and high cardiovascular risk&#46; The patients treated with canagliflozin had a 14&#37; reduction &#40;hazard ratio &#91;HR&#93;&#44; 0&#46;8&#59; 95&#37; confidence interval &#91;95&#37; CI&#93; 0&#46;75&#8211;0&#46;97&#41; in the risk of events included globally in the primary endpoint &#40;a composite of death by cardiovascular cause&#44; nonfatal myocardial infarction and nonfatal stroke&#41;&#46; Statistical significance was not reached&#44; however&#44; in reducing each of these events separately&#46; Hospitalization for heart failure was reduced by 33&#37; &#40;HR&#44; 0&#46;67&#59; 95&#37; CI 0&#46;52&#8211;0&#46;87&#41;&#46; The results showed renal benefits with canagliflozin&#44; reducing both the progression of albuminuria &#40;HR&#44; 0&#46;73&#59; 95&#37; CI 0&#46;67&#8211;0&#46;79&#41; and the composite result of a sustained reduction of 40&#37; in the estimated glomerular filtration rate and death by renal causes &#40;HR&#44; 0&#46;60&#59; 95&#37; CI 0&#46;47&#8211;0&#46;77&#41;&#46; A more detailed analysis of these results is being performed&#44; which has still not been incorporated in the international recommendations&#46;</p><p id="par0280" class="elsevierStylePara elsevierViewall">The most common adverse effect of these drugs is genital mycoses&#44; especially in women&#46; A slight increase has also been reported in urinary tract infections&#46;<a class="elsevierStyleCrossRef" href="#bib1645"><span class="elsevierStyleSup">144</span></a> In elderly individuals&#44; we should consider the potential adverse effects related to volume depletion secondary to osmotic diuresis &#40;dehydration&#44; electrolyte disorders&#44; hypotension and renal failure&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1650"><span class="elsevierStyleSup">145</span></a> Given the drugs&#8217; hypotensive effect&#44; it is important to rule out the presence of orthostatic hypotension&#44; which is common in elderly patients with diabetes&#46;<a class="elsevierStyleCrossRef" href="#bib1655"><span class="elsevierStyleSup">146</span></a> Although a study with canagliflozin observed an increased number of fractures &#40;extremities but not hip&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib1660"><span class="elsevierStyleSup">147</span></a> possibly related to an increased risk of falls&#44; this association was not confirmed in a subsequent study&#46;<a class="elsevierStyleCrossRef" href="#bib1665"><span class="elsevierStyleSup">148</span></a> The CANVAS study confirmed a greater tendency for fractures in patients treated with canagliflozin versus placebo &#40;HR&#44; 1&#46;23&#59; 95&#37; CI 0&#46;99&#8211;1&#46;52&#41;&#46; In this study&#44; treatment with canagliflozin was associated with a higher risk of amputation&#44; mainly of toes and the metatarsal &#40;6&#46;3 vs&#46; 3&#46;4 participants with amputation per 1000 patient-years&#44; which corresponds to a risk ratio of 1&#46;97&#59; 95&#37; CI 1&#46;41&#8211;2&#46;75&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1645"><span class="elsevierStyleSup">144</span></a> Finally&#44; rare cases of normoglycemic ketoacidosis have been reported &#40;with only slightly elevated blood glucose readings&#41;&#44; especially in long-standing DM2 in conditions of insulinopenia or latent autoimmune diabetes in adults in which an insulin dose reduction was performed&#46; Normoglycemic ketoacidosis has also been reported in fasting conditions&#44; with excessive alcohol consumption&#44; extreme physical exercise and intercurrent acute processes&#46;<a class="elsevierStyleCrossRef" href="#bib1670"><span class="elsevierStyleSup">149</span></a></p><p id="par0285" class="elsevierStylePara elsevierViewall">The action of these drugs depends on the renal function&#44; such that their efficacy decreases when the glomerular filtration rate is &#60;60<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#46;72<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#46; Dapagliflozin should not be administered below this filtration rate&#59; however&#44; empagliflozin and canagliflozin may be used&#44; with reduced dosages&#44;<a class="elsevierStyleCrossRefs" href="#bib1675"><span class="elsevierStyleSup">150&#44;151</span></a> for GFRs between 45 and 60<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#46;72<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> and discontinued for GFRs &#60;30<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#46;72<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#46;</p><p id="par0290" class="elsevierStylePara elsevierViewall">There is little experience on the use of SGLT2 inhibitors in the elderly population and should therefore be indicated with caution and individually in selected patients&#46;<a class="elsevierStyleCrossRef" href="#bib1685"><span class="elsevierStyleSup">152</span></a> Canagliflozin has had a number of studies with elderly patients of up to 80 years of age&#44; which has shown a safety and efficacy comparable to that with younger patients&#46;<a class="elsevierStyleCrossRefs" href="#bib1650"><span class="elsevierStyleSup">145&#44;147&#44;148&#44;153&#8211;155</span></a> Furthermore&#44; the analysis by age subgroup with empagliflozin<a class="elsevierStyleCrossRef" href="#bib1620"><span class="elsevierStyleSup">139</span></a> and dapagliflozin<a class="elsevierStyleCrossRefs" href="#bib1705"><span class="elsevierStyleSup">156&#8211;158</span></a> has shown similar results to those obtained in younger patients&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Insulin</span><p id="par0295" class="elsevierStylePara elsevierViewall">Insulin is the most potent hypoglycemic agent and acts by activating the insulin receptors&#44; decreasing glucose production by the liver and promoting the peripheral use of glucose&#46; In Spain&#44; 20&#37; of patients with diabetes older than 75 years were treated with insulin in monotherapy or combined with other antidiabetic agents&#46;<a class="elsevierStyleCrossRef" href="#bib1720"><span class="elsevierStyleSup">159</span></a></p><p id="par0300" class="elsevierStylePara elsevierViewall">Patients older than 80 years treated with insulin have a greater risk of severe hypoglycemia&#44;<a class="elsevierStyleCrossRef" href="#bib1060"><span class="elsevierStyleSup">27</span></a> falls and fractures&#46;<a class="elsevierStyleCrossRef" href="#bib1725"><span class="elsevierStyleSup">160</span></a> To minimize these risks&#44; insulin therapy for the elderly should be individualized&#44; emphasizing patient safety&#46; It is worth remembering that HbA1c levels are not a reliable predictor of the risk of hypoglycemia&#46;<a class="elsevierStyleCrossRef" href="#bib1730"><span class="elsevierStyleSup">161</span></a></p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Basal insulinization</span><p id="par0305" class="elsevierStylePara elsevierViewall">The starting daily dose should be lower &#40;0&#46;1&#8211;0&#46;2<span class="elsevierStyleHsp" style=""></span>IU&#47;kg&#41; than for younger patients with DM2&#44; especially for frail elderly patients&#44; those with low weight and those with renal failure&#46; Dose adjustments should be performed gradually and progressively&#46;</p><p id="par0310" class="elsevierStylePara elsevierViewall">When treatment is started with a basal insulin&#44; it is recommended that the treatment with metformin be maintained to reduce the insulin requirements&#46;<a class="elsevierStyleCrossRef" href="#bib1735"><span class="elsevierStyleSup">162</span></a> The combination of basal insulin and oral secretagogues &#40;sulfonylureas&#44; glinides&#41; is not safe for elderly patients due to the high risk of hypoglycemia&#46; The maintenance or discontinuation of other noninsulin antidiabetic drugs should be individually assessed&#44; considering the complexity of the treatment and its costs&#46;<a class="elsevierStyleCrossRef" href="#bib1735"><span class="elsevierStyleSup">162</span></a></p><p id="par0315" class="elsevierStylePara elsevierViewall">Although they have not demonstrated superiority in glycemic control&#44; basal insulin analogs &#40;glargine 100<span class="elsevierStyleHsp" style=""></span>U and 300<span class="elsevierStyleHsp" style=""></span>U&#44; detemir&#44; degludec&#41; have a lower risk of hypoglycemia &#40;especially nocturnal&#41; than human neutral protamine Hagedorn insulin&#44;<a class="elsevierStyleCrossRefs" href="#bib1740"><span class="elsevierStyleSup">163&#8211;165</span></a> and can therefore be preferable for elderly patients despite the drugs&#8217; higher cost&#46; Compared with insulin glargine 100<span class="elsevierStyleHsp" style=""></span>U&#44; both insulin glargine 300U<a class="elsevierStyleCrossRef" href="#bib1755"><span class="elsevierStyleSup">166</span></a> and insulin degludec<a class="elsevierStyleCrossRefs" href="#bib1760"><span class="elsevierStyleSup">167&#44;168</span></a> have shown a lower rate of hypoglycemia &#40;especially nocturnal&#41; and greater flexibility in the administration schedule&#44; due to their lower variability and longer drug action&#46; These characteristics favorably place these new insulins for the management of elderly institutionalized patients&#44; although studies are needed on this population&#46;<a class="elsevierStyleCrossRef" href="#bib1770"><span class="elsevierStyleSup">169</span></a></p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Basal insulin intensification</span><p id="par0320" class="elsevierStylePara elsevierViewall">When the glycemic control objectives are not met with a basal insulin regimen&#44; the insulin therapy needs to be intensified&#44; either by adding a dose of prandial insulin in the main meal &#40;basal-plus&#41;&#44; in the 3 main meals &#40;basal-bolus&#41; or transitioning to a regimen of 2 or 3 daily doses of premixed insulin&#46; These complex insulin therapy regimens are associated with a significant risk of hypoglycemia<a class="elsevierStyleCrossRefs" href="#bib1740"><span class="elsevierStyleSup">163&#44;170&#44;171</span></a> and represent a significant burden of care&#44; including the need for repeated capillary blood glucose checks&#46;</p><p id="par0325" class="elsevierStylePara elsevierViewall">If prandial insulin is required&#44; rapid-acting insulin analogs are preferable to regular insulin due the former&#39;s lower rate of hypoglycemia&#46;<a class="elsevierStyleCrossRef" href="#bib1785"><span class="elsevierStyleSup">172</span></a> Biphasic or premixed insulins&#44; such as insulin aspart and insulin glulisine&#44; can be administered after meals<a class="elsevierStyleCrossRefs" href="#bib1775"><span class="elsevierStyleSup">170&#44;173&#44;174</span></a> and improve glycemic control in patients poorly controlled with basal insulin but are associated with a higher risk of hypoglycemia and weight gain&#46;<a class="elsevierStyleCrossRefs" href="#bib1780"><span class="elsevierStyleSup">171&#44;175</span></a> Premixed insulins have an inflexible pharmacokinetic profile and are therefore only indicated for elderly patients with regular schedules and patterns of dietary intake and physical activity&#46; In these cases&#44; premixed insulins can provide glycemic control similar to that of the more complex basal-bolus regimen&#46;<a class="elsevierStyleCrossRef" href="#bib1805"><span class="elsevierStyleSup">176</span></a></p><p id="par0330" class="elsevierStylePara elsevierViewall">In elderly patients with difficult-to-control or highly progressed DM2 with insulinopenia and a good capacity for self-care&#44; the basal-bolus regimen can provide appropriate glycemic control with a good safety profile and patient satisfaction&#46;<a class="elsevierStyleCrossRef" href="#bib1810"><span class="elsevierStyleSup">177</span></a></p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Insulin devices</span><p id="par0335" class="elsevierStylePara elsevierViewall">Another issue to consider is the various devices for administering insulin and choosing that which best fits the patient&#39;s abilities and capabilities&#46; By far&#44; the most widely used is the pen type&#46; To detect elderly patients with problems in self-administering insulin&#44; a test known as the &#8220;clock-drawing test&#8221; is employed to assess cognitive impairment and the presence of constructional apraxia&#46;<a class="elsevierStyleCrossRef" href="#bib1815"><span class="elsevierStyleSup">178</span></a> The test consists of having the patient draw &#40;on a blank sheet of paper&#41; a clock indicating ten past eleven&#46;</p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Combined therapies</span><p id="par0340" class="elsevierStylePara elsevierViewall">In the elderly&#44; it is essential to simplify insulin therapy as much as possible to reduce the risk of hypoglycemia and minimize the burden of care associated with the complex insulin regimens&#46;<a class="elsevierStyleCrossRef" href="#bib1730"><span class="elsevierStyleSup">161</span></a> As has been mentioned&#44; oral diabetes drugs should be maintained &#40;except for sulfonylureas&#47;glinides&#41; with the basal insulin to reduce the insulin requirements and risks of hypoglycemia&#46;<a class="elsevierStyleCrossRefs" href="#bib1735"><span class="elsevierStyleSup">162&#44;179</span></a> DPP4i have an especially appropriate profile in this population due to their low risk of hypoglycemia and broad experience with their use in elderly patients with frailty and renal failure&#46; Their combination with basal insulin allows for the insulin dosage to be reduced and minimizes the adverse effects of the insulin &#40;hypoglycemia&#44; weight gain&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1825"><span class="elsevierStyleSup">180</span></a></p><p id="par0345" class="elsevierStylePara elsevierViewall">The combined therapy of basal insulin and GLP-1 RA provides excellent glycemic control and a lower risk of hypoglycemia than the complex insulin regimens&#46;<a class="elsevierStyleCrossRef" href="#bib1830"><span class="elsevierStyleSup">181</span></a> There have been studies with fixed-dose combinations of basal insulin and GLP-1 RA &#40;degludec and liraglutide&#59; glargine and lixisenatide&#41; that facilitate the posology and improve the gastrointestinal tolerance to GLP-1 RA&#46; These combinations can therefore play a role in treating DM2 in the elderly&#46; Nevertheless&#44; the lesser experience with using these combinations in the elderly&#44; a lack of specific studies and the combinations&#8217; higher cost make careful patient selection a necessity&#46;</p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Therapy deintensification</span><p id="par0350" class="elsevierStylePara elsevierViewall">Elderly patients with diabetes are frequently overtreated&#46;<a class="elsevierStyleCrossRefs" href="#bib1030"><span class="elsevierStyleSup">21&#44;22</span></a> Antidiabetic therapy deintensification is therefore appropriate after a comprehensive geriatric assessment has been conducted&#44; indicating less complex and safer regimens &#40;with a lower risk of hypoglycemia&#44; lower burden of care&#44; better tolerance and no drug interactions&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1835"><span class="elsevierStyleSup">182</span></a> The simplification of complex insulin regimens in elderly patients reduces the risk of hypoglycemia and the burden of care&#44; without compromising glycemic control&#46;<a class="elsevierStyleCrossRef" href="#bib1730"><span class="elsevierStyleSup">161</span></a> In this respect&#44; it is worth remembering that a high HbA1c level does not rule out the risk of hypoglycemia in the elderly&#46;<a class="elsevierStyleCrossRefs" href="#bib1050"><span class="elsevierStyleSup">25&#44;161</span></a></p></span></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Therapeutic algorithm for type 2 diabetes in elderly patients &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;</span><p id="par0355" class="elsevierStylePara elsevierViewall"> The planning of DM2 therapy for elderly patients should be based on a comprehensive geriatric assessment&#46; If the elderly patient is frail&#44; dependent or has moderate to severe dementia&#44; the priority objective is to prevent symptomatic hypoglycemia and hyperglycemia&#46; The antidiabetic agents recommended in these cases would be metformin and DPP4i&#46; Other antidiabetic drugs not associated with a significant risk of hypoglycemia have adverse effects that limit their use in this population&#44; effects such as hypotension&#44; dehydration and renal failure &#40;with SGLT2i&#41; and nausea&#44; vomiting&#44; diarrhea and weight loss &#40;with GLP-1 RA&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0360" class="elsevierStylePara elsevierViewall">Renal failure is a prevalent comorbidity in elderly patients with diabetes and affects the treatment options&#46;<a class="elsevierStyleCrossRef" href="#bib1840"><span class="elsevierStyleSup">183</span></a> In Spain&#44; the prevalence of stage 4 and 5 chronic kidney disease &#40;glomerular filtration rate &#60;30<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#41; in patients with DM2 aged 70&#8211;79 years and &#8805;80 years is approximately 30&#37; and 50&#37;&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib1845"><span class="elsevierStyleSup">184</span></a> In these circumstances&#44; the preferred therapeutic options are DPP4i and insulin&#46; Although repaglinide and pioglitazone may be used from a pharmacokinetic standpoint&#44; their adverse effects profile &#40;hypoglycemia with repaglinide&#59; heart failure and fractures with pioglitazone&#41; make them an inadvisable option&#46;<a class="elsevierStyleCrossRef" href="#bib1850"><span class="elsevierStyleSup">185</span></a></p><p id="par0365" class="elsevierStylePara elsevierViewall">Finally&#44; for elderly patients with a high cardiovascular risk and none of the previously mentioned clinical limitations &#40;moderate&#8211;severe renal failure&#44; frailty&#44; dementia&#41;&#44; the priority should be to select antidiabetic drugs that have shown cardiovascular benefits&#44; such as empagliflozin and liraglutide&#46; Other drugs that have shown cardiovascular safety include metformin&#44; pioglitazone and DPP4i&#46;</p></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Conflict of interest</span><p id="par0370" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:14 [
        0 => array:3 [
          "identificador" => "xres991073"
          "titulo" => "Abstract"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abst0005"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec954991"
          "titulo" => "Keywords"
        ]
        2 => array:3 [
          "identificador" => "xres991072"
          "titulo" => "Resumen"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abst0010"
            ]
          ]
        ]
        3 => array:2 [
          "identificador" => "xpalclavsec954992"
          "titulo" => "Palabras clave"
        ]
        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Background"
        ]
        5 => array:2 [
          "identificador" => "sec0010"
          "titulo" => "Functional capacity&#44; frailty and diabetes"
        ]
        6 => array:2 [
          "identificador" => "sec0015"
          "titulo" => "Hypoglycemia in elderly patients"
        ]
        7 => array:2 [
          "identificador" => "sec0020"
          "titulo" => "General principles in the treatment of elderly patients with type 2 diabetes"
        ]
        8 => array:2 [
          "identificador" => "sec0025"
          "titulo" => "Glycemic control objectives for elderly patients"
        ]
        9 => array:2 [
          "identificador" => "sec0030"
          "titulo" => "Nonpharmacological treatment&#58; nutrition and physical activity"
        ]
        10 => array:3 [
          "identificador" => "sec0035"
          "titulo" => "Pharmacotherapy"
          "secciones" => array:14 [
            0 => array:2 [
              "identificador" => "sec0040"
              "titulo" => "Metformin"
            ]
            1 => array:2 [
              "identificador" => "sec0045"
              "titulo" => "Sulfonylureas"
            ]
            2 => array:2 [
              "identificador" => "sec0050"
              "titulo" => "Meglitinides &#40;repaglinide&#44; nateglinide&#41;"
            ]
            3 => array:2 [
              "identificador" => "sec0055"
              "titulo" => "Alpha-glucosidase inhibitors &#40;acarbose&#44; miglitol&#41;"
            ]
            4 => array:2 [
              "identificador" => "sec0060"
              "titulo" => "Thiazolidinediones &#40;pioglitazone&#41;"
            ]
            5 => array:2 [
              "identificador" => "sec0065"
              "titulo" => "Dipeptidyl peptidase-4 inhibitors &#40;sitagliptin&#44; vildagliptin&#44; saxagliptin&#44; linagliptin&#44; alogliptin&#41;"
            ]
            6 => array:2 [
              "identificador" => "sec0070"
              "titulo" => "Glucagon-like peptide-1 receptor agonists &#40;exenatide&#44; liraglutide&#44; lixisenatide&#44; exenatide-LAR&#44; dulaglutide&#41;"
            ]
            7 => array:2 [
              "identificador" => "sec0075"
              "titulo" => "Sodium-glucose cotransporter 2 inhibitors &#40;dapagliflozin&#44; canagliflozin&#44; empagliflozin&#41;"
            ]
            8 => array:2 [
              "identificador" => "sec0080"
              "titulo" => "Insulin"
            ]
            9 => array:2 [
              "identificador" => "sec0085"
              "titulo" => "Basal insulinization"
            ]
            10 => array:2 [
              "identificador" => "sec0090"
              "titulo" => "Basal insulin intensification"
            ]
            11 => array:2 [
              "identificador" => "sec0095"
              "titulo" => "Insulin devices"
            ]
            12 => array:2 [
              "identificador" => "sec0100"
              "titulo" => "Combined therapies"
            ]
            13 => array:2 [
              "identificador" => "sec0105"
              "titulo" => "Therapy deintensification"
            ]
          ]
        ]
        11 => array:2 [
          "identificador" => "sec0110"
          "titulo" => "Therapeutic algorithm for type 2 diabetes in elderly patients &#40;Fig&#46; 1&#41;"
        ]
        12 => array:2 [
          "identificador" => "sec0115"
          "titulo" => "Conflict of interest"
        ]
        13 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2017-10-11"
    "fechaAceptado" => "2017-12-03"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec954991"
          "palabras" => array:3 [
            0 => "Type 2 diabetes mellitus"
            1 => "Elderly"
            2 => "Antidiabetic treatment"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec954992"
          "palabras" => array:3 [
            0 => "Diabetes mellitus tipo 2"
            1 => "Anciano"
            2 => "Tratamiento antidiab&#233;tico"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The prevalence of type 2 diabetes mellitus &#40;DM2&#41; increases markedly with age&#46; Antidiabetic treatment and the objectives of glycaemic control in elderly patients with DM2 should be individualized according to their biopsychosocial characteristics&#46; In elderly patients for whom the benefits of intensive antidiabetic treatment are limited&#44; the basic objectives should be to improve the quality of life&#44; preserve functionality and avoid adverse effects&#44; especially hypoglycaemia&#46; Treatment of DM2 in the elderly was the subject of a consensus document published in 2012 and endorsed by several Spanish scientific societies&#46; Since then&#44; new therapeutic groups and evidence have emerged that warrant an update to this consensus document&#46; The present document focuses on the therapeutic aspects of DM2 in elderly patients&#44; understood as being older than 75 years or frail&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La prevalencia de la diabetes mellitus tipo 2 &#40;DM2&#41; se incrementa marcadamente con la edad&#46; El tratamiento antidiab&#233;tico y los objetivos de control gluc&#233;mico en el anciano con DM2 deben individualizarse en funci&#243;n de sus caracter&#237;sticas biopsicosociales&#46; En los pacientes de edad avanzada&#44; en los que los beneficios de un tratamiento antidiab&#233;tico intensivo son limitados&#44; los objetivos b&#225;sicos deben ser mejorar la calidad de vida&#44; preservar la funcionalidad y evitar los efectos adversos&#44; muy especialmente las hipoglucemias&#46; El tratamiento de la DM2 en el anciano fue objeto de un consenso&#44; publicado en 2012 y avalado por varias sociedades cient&#237;ficas espa&#241;olas&#46; Desde entonces&#44; han aparecido nuevos grupos terap&#233;uticos y evidencias que hacen recomendable su actualizaci&#243;n&#46; El presente documento se centrar&#225; en los aspectos terap&#233;uticos de la DM2 en el paciente anciano&#44; entendiendo como tal el tener una edad mayor de 75 a&#241;os o presentar fragilidad&#46;</p></span>"
      ]
    ]
    "NotaPie" => array:2 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; G&#243;mez-Huelgas R&#44; G&#243;mez Peralta F&#44; Rodr&#237;guez Ma&#241;as L&#44; Formiga F&#44; Puig Domingo M&#44; Mediavilla Bravo JJ&#44; et al&#46; Tratamiento de la diabetes mellitus tipo 2 en el paciente anciano&#46; Rev Clin Esp&#46; 2018&#59;218&#58;74&#8211;88&#46;</p>"
      ]
      1 => array:2 [
        "etiqueta" => "&#9734;&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">This article is published simultaneously in <span class="elsevierStyleInterRef" id="intr0010" href="https://doi.org/10.1016/j.regg.2017.12.003">https&#58;&#47;&#47;doi&#46;org&#47;10&#46;1016&#47;j&#46;regg&#46;2017&#46;12&#46;003</span>&#44; with the consent of the authors and editors&#46;</p>"
      ]
    ]
    "multimedia" => array:2 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1519
            "Ancho" => 2506
            "Tamanyo" => 258442
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Treatment algorithm for type 2 diabetes mellitus in elderly patients&#46;</p> <p id="spar0020" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; DPP4i&#58; dipeptidyl peptidase-4 inhibitors&#59; GLP-1RA&#58; glucagon-like peptide-1 receptor agonists&#59; SGLT2i&#58; sodium-glucose cotransporter 2 inhibitors&#46;</p> <p id="spar0025" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">a</span> Repaglinide and pioglitazone can be used in patients with GFR &#60;30<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#44; but their use is not recommended due to the risk of adverse effects&#58; hypoglycemia &#40;repaglinide&#41;&#59; salt and fluid retention&#44; heart failure and fractures &#40;pioglitazone&#41;&#46;</p> <p id="spar0030" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">b</span> Empagliflozin&#44; canagliflozin and liraglutide have shown reduced cardiovascular morbidity and mortality in patients with high vascular risk type 2 diabetes&#46;</p> <p id="spar0035" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">c</span> Saxagliptin should be avoided for patients with heart failure&#46;</p> <p id="spar0040" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">d</span> Pioglitazone is contraindicated for patients with heart failure or at risk for fractures&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">We considered the presence of the frailty phenotype when the patient met 3 or more criteria and the prefrailty phenotype when 1 or 2 criteria were met&#46;</p><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviation</span>&#58; BMI&#44; body mass index&#46;</p><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Taken from Fried et al&#46;<a class="elsevierStyleCrossRef" href="#bib0935"><span class="elsevierStyleSup">2</span></a></p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Marker&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Assessment tool&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Spontaneous weight loss&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Unexplained loss &#62;4&#46;5<span class="elsevierStyleHsp" style=""></span>kg or &#62;5&#37; of the weight in the last year&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Fatigue&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Self-reported fatigue&#44; identified by a score &#62;2 on the Center Epidemiological Studies-Depression scale &#40;0&#8211;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Muscle weakness&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Grip strength &#40;dynamometer&#41; &#60;20&#37; of normal&#44; adjusted for BMI and sex&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Motor retardation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Gait speed for covering 4&#46;5<span class="elsevierStyleHsp" style=""></span>m &#60;20&#37; of normal&#44; adjusted for sex and height &#40;&#62;6&#8211;7<span class="elsevierStyleHsp" style=""></span>s&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Hypoactivity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Weekly calorie expenditure below the lower quintile&#44; adjusted for sex &#40;men &#60;383<span class="elsevierStyleHsp" style=""></span>kcal&#47;week&#44; women &#60;270<span class="elsevierStyleHsp" style=""></span>kcal&#47;week&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1678923.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Fried frailty criteria&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:185 [
            0 => array:3 [
              "identificador" => "bib0930"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Diabetes in older people&#58; new insights and remaining challenges"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S2213-8587(14)70176-7"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0935"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Frailty in older adults&#58; evidence for a phenotype"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0940"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:3 [
                  "comentario" => "Available from&#58; <span class="elsevierStyleInterRef" id="intr0015" href="http://www.unpopulation.org/">www&#46;unpopulation&#46;org</span> &#91;accessed 06&#46;11&#46;17&#93;"
                  "contribucion" => array:1 [
                    0 => array:1 [
                      "titulo" => "Population ageing and development"
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:1 [ …1]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0945"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Evoluci&#243;n de los indicadores de calidad asistencial al diab&#233;tico tipo 2 en atenci&#243;n primaria &#40;1996&#8211;2007&#41;"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [ …5]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0950"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prevalence of diabetes mellitus and impaired glucose regulation in Spain&#58; the Di&#64;bet&#46;es study"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00125-011-2336-9"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0955"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Federaci&#243;n Internacional de la Diabetes&#46; Atlas de la diabetes&#46; 6&#46;&#170; ed&#46; Actualizaci&#243;n&#59; 2014 &#91;accessed 11&#46;10&#46;17&#93;&#46; Available from&#58; <a href="http://www.idf.org/diabetesatlas">www&#46;idf&#46;org&#47;diabetesatlas</a>&#46;"
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0960"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A call for action in diabetes care for older people"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1464-5491.2011.03335.x"
                      "Revista" => array:7 [ …7]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0965"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:3 [
                  "comentario" => "134e1&#8211;e12"
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tratamiento de la diabetes tipo 2 en el paciente anciano"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [ …3]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0970"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Untangling the concepts of disability&#44; frailty&#44; and comorbidity&#58; implications for improved targeting and care"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0975"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Frailty as a major factor in the increased risk of death and disability in older people with diabetes"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jamda.2016.07.013"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0980"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Comparison of the prognostic importance of diagnosed diabetes&#44; co-morbidity and frailty in older people"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1464-5491.2010.02977.x"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0985"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Diabetes and risk of frailty and its potential mechanisms&#58; a prospective cohort study of older adults"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jamda.2015.04.008"
                      "Revista" => array:7 [ …7]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0990"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The third transition&#58; the clinical evolution oriented to the contemporary older patient"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jamda.2016.10.005"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0995"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Fragilidad&#58; &#191;de qu&#233; estamos hablando&#63; Implicaciones para la pr&#225;ctica cl&#237;nica diaria"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.regg.2017.04.004"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib1000"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The effect of comorbid illness and functional status on the expected benefits of intensive glucose control in older patients with type 2 diabetes&#58; a decision analysis"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib1005"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The risks and benefits of implementing glycemic control guidelines in frail older adults with diabetes mellitus"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1532-5415.2011.03362.x"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib1010"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Glycemic control and functional decline in nursing home residents with diabetes"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/jamainternmed.2016.6949"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib1015"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "SGS&#58; a structured treatment and teaching programme for older patients with diabetes mellitus&#8212;a prospective randomised controlled multi-centre trial"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/ageing/afp056"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib1020"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Incidence and care-related costs of severe hypoglycaemia requiring emergency treatment in Andalusia &#40;Spain&#41;&#58; the PAUEPAD project"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/dme.12843"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib1025"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The frequency and impact of hypoglycemia among hospitalized patients with diabetes&#58; a population-based study"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [ …5]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib1030"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Potential overtreatment of diabetes mellitus in older adults with tight glycemic control"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/jamainternmed.2014.7345"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib1035"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inadequate glycaemic control and therapeutic management of adults over 65 years old with type 2 diabetes mellitus in Spain"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s12603-017-0869-4"
                      "Revista" => array:2 [ …2]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib1040"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Emergency hospitalizations for adverse drug events in older Americans"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMsa1103053"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib1045"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hypoglycemia unawareness in older compared with middle-aged patients with type 2 diabetes"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2337/dc09-0114"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib1050"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Frequent hypoglycemia among elderly patients with poor glycemic control"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/archinternmed.2010.539"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib1055"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Severe hypoglycaemia and cognitive impairment in older patients with diabetes&#58; the Fremantle Diabetes Study"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00125-009-1437-1"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib1060"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "National estimates of insulin-related hypoglycemia and errors leading to emergency department visits and hospitalizations"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/jamainternmed.2014.136"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib1065"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "National trends in US hospital admissions for hyperglycemia and hypoglycemia among Medicare beneficiaries&#44; 1999 to 2011"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/jamainternmed.2014.1824"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib1070"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Relationship between hypoglycemic episodes and ventricular arrhythmias in patients with type 2 diabetes and cardiovascular diseases&#58; silent hypoglycemias and silent arrhythmias"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2337/dc13-0600"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib1075"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "New IDF Guideline for managing type 2 diabetes in older people"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.diabres.2014.03.005"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib1080"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "11&#46; Older adults"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2337/dc17-S014"
                      "Revista" => array:7 [ …7]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib1085"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Glycemic control&#44; complications&#44; and death in older diabetic patients&#58; the diabetes and aging study"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2337/dc10-2377"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib1090"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "An approach to diabetes mellitus in hospice and palliative medicine"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1089/jpm.2010.0191"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib1095"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "An evaluation of the effectiveness of a multi-modal intervention in frail and pre-frail older people with type 2 diabetes&#8212;the MID-Frail study&#58; study protocol for a randomised controlled trial"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/1745-6215-15-34"
                      "Revista" => array:5 [ …5]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib1100"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The look AHEAD study&#58; implications for clinical practice go beyond the headlines"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jand.2014.01.008"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            35 => array:3 [
              "identificador" => "bib1105"
              "etiqueta" => "36"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Intensive weight loss intervention in older individuals&#58; results from the Action for Health in Diabetes Type 2 diabetes mellitus trial"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/jgs.12271"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            36 => array:3 [
              "identificador" => "bib1110"
              "etiqueta" => "37"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Aging and physical function in type 2 diabetes&#58; 8 years of an intensive lifestyle intervention"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/gerona/glu083"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            37 => array:3 [
              "identificador" => "bib1115"
              "etiqueta" => "38"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Nutrition education improves metabolic outcomes among older adults with diabetes mellitus&#58; results from a randomized controlled trial"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1006/pmed.2001.0985"
                      "Revista" => array:7 [ …7]
                    ]
                  ]
                ]
              ]
            ]
            38 => array:3 [
              "identificador" => "bib1120"
              "etiqueta" => "39"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The effect of diabetes mellitus on age-associated lean mass loss in 3153 older adults"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1464-5491.2010.03118.x"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            39 => array:3 [
              "identificador" => "bib1125"
              "etiqueta" => "40"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Fat infiltration of muscle&#44; diabetes&#44; and clinical fracture risk in older adults"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1210/jc.2010-0780"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            40 => array:3 [
              "identificador" => "bib1130"
              "etiqueta" => "41"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Diabetes and exercise in the elderly"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1159/000357342"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            41 => array:3 [
              "identificador" => "bib1135"
              "etiqueta" => "42"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Lessened decline in physical activity and impairment of older adults with diabetes with telemedicine and pedometer use&#58; results from the IDEATel study"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/ageing/afq147"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            42 => array:3 [
              "identificador" => "bib1140"
              "etiqueta" => "43"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Short-term aerobic exercise reduces arterial stiffness in older adults with type 2 diabetes&#44; hypertension&#44; and hypercholesterolemia"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            43 => array:3 [
              "identificador" => "bib1145"
              "etiqueta" => "44"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            44 => array:3 [
              "identificador" => "bib1150"
              "etiqueta" => "45"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:1 [ …1]
                  ]
                ]
              ]
            ]
            45 => array:3 [
              "identificador" => "bib1155"
              "etiqueta" => "46"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:1 [ …1]
                  ]
                ]
              ]
            ]
            46 => array:3 [
              "identificador" => "bib1160"
              "etiqueta" => "47"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:1 [ …1]
                  ]
                ]
              ]
            ]
            47 => array:3 [
              "identificador" => "bib1165"
              "etiqueta" => "48"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            48 => array:3 [
              "identificador" => "bib1170"
              "etiqueta" => "49"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            49 => array:3 [
              "identificador" => "bib1175"
              "etiqueta" => "50"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            50 => array:3 [
              "identificador" => "bib1180"
              "etiqueta" => "51"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            51 => array:3 [
              "identificador" => "bib1185"
              "etiqueta" => "52"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            52 => array:3 [
              "identificador" => "bib1190"
              "etiqueta" => "53"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            53 => array:3 [
              "identificador" => "bib1195"
              "etiqueta" => "54"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            54 => array:3 [
              "identificador" => "bib1200"
              "etiqueta" => "55"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            55 => array:3 [
              "identificador" => "bib1205"
              "etiqueta" => "56"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            56 => array:3 [
              "identificador" => "bib1210"
              "etiqueta" => "57"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            57 => array:3 [
              "identificador" => "bib1215"
              "etiqueta" => "58"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:1 [ …1]
                  ]
                ]
              ]
            ]
            58 => array:3 [
              "identificador" => "bib1220"
              "etiqueta" => "59"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            59 => array:3 [
              "identificador" => "bib1225"
              "etiqueta" => "60"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            60 => array:3 [
              "identificador" => "bib1230"
              "etiqueta" => "61"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            61 => array:3 [
              "identificador" => "bib1235"
              "etiqueta" => "62"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:1 [ …1]
                  ]
                ]
              ]
            ]
            62 => array:3 [
              "identificador" => "bib1240"
              "etiqueta" => "63"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:1 [ …1]
                  ]
                ]
              ]
            ]
            63 => array:3 [
              "identificador" => "bib1245"
              "etiqueta" => "64"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            64 => array:3 [
              "identificador" => "bib1250"
              "etiqueta" => "65"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:1 [ …1]
                  ]
                ]
              ]
            ]
            65 => array:3 [
              "identificador" => "bib1255"
              "etiqueta" => "66"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            66 => array:3 [
              "identificador" => "bib1260"
              "etiqueta" => "67"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            67 => array:3 [
              "identificador" => "bib1265"
              "etiqueta" => "68"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            68 => array:3 [
              "identificador" => "bib1270"
              "etiqueta" => "69"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:1 [ …1]
                  ]
                ]
              ]
            ]
            69 => array:3 [
              "identificador" => "bib1275"
              "etiqueta" => "70"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            70 => array:3 [
              "identificador" => "bib1280"
              "etiqueta" => "71"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:1 [ …1]
                  ]
                ]
              ]
            ]
            71 => array:3 [
              "identificador" => "bib1285"
              "etiqueta" => "72"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:1 [ …1]
                  ]
                ]
              ]
            ]
            72 => array:3 [
              "identificador" => "bib1290"
              "etiqueta" => "73"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            73 => array:3 [
              "identificador" => "bib1295"
              "etiqueta" => "74"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            74 => array:3 [
              "identificador" => "bib1300"
              "etiqueta" => "75"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            75 => array:3 [
              "identificador" => "bib1305"
              "etiqueta" => "76"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:1 [ …1]
                  ]
                ]
              ]
            ]
            76 => array:3 [
              "identificador" => "bib1310"
              "etiqueta" => "77"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            77 => array:3 [
              "identificador" => "bib1315"
              "etiqueta" => "78"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            78 => array:3 [
              "identificador" => "bib1320"
              "etiqueta" => "79"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            79 => array:3 [
              "identificador" => "bib1325"
              "etiqueta" => "80"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            80 => array:3 [
              "identificador" => "bib1330"
              "etiqueta" => "81"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            81 => array:3 [
              "identificador" => "bib1335"
              "etiqueta" => "82"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:1 [ …1]
                  ]
                ]
              ]
            ]
            82 => array:3 [
              "identificador" => "bib1340"
              "etiqueta" => "83"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            83 => array:3 [
              "identificador" => "bib1345"
              "etiqueta" => "84"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            84 => array:3 [
              "identificador" => "bib1350"
              "etiqueta" => "85"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:1 [ …1]
                  ]
                ]
              ]
            ]
            85 => array:3 [
              "identificador" => "bib1355"
              "etiqueta" => "86"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            86 => array:3 [
              "identificador" => "bib1360"
              "etiqueta" => "87"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:1 [ …1]
                  ]
                ]
              ]
            ]
            87 => array:3 [
              "identificador" => "bib1365"
              "etiqueta" => "88"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            88 => array:3 [
              "identificador" => "bib1370"
              "etiqueta" => "89"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            89 => array:3 [
              "identificador" => "bib1375"
              "etiqueta" => "90"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            90 => array:3 [
              "identificador" => "bib1380"
              "etiqueta" => "91"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            91 => array:3 [
              "identificador" => "bib1385"
              "etiqueta" => "92"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            92 => array:3 [
              "identificador" => "bib1390"
              "etiqueta" => "93"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            93 => array:3 [
              "identificador" => "bib1395"
              "etiqueta" => "94"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            94 => array:3 [
              "identificador" => "bib1400"
              "etiqueta" => "95"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:1 [ …1]
                  ]
                ]
              ]
            ]
            95 => array:3 [
              "identificador" => "bib1405"
              "etiqueta" => "96"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            96 => array:3 [
              "identificador" => "bib1410"
              "etiqueta" => "97"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            97 => array:3 [
              "identificador" => "bib1415"
              "etiqueta" => "98"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            98 => array:3 [
              "identificador" => "bib1420"
              "etiqueta" => "99"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            99 => array:3 [
              "identificador" => "bib1425"
              "etiqueta" => "100"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            100 => array:3 [
              "identificador" => "bib1430"
              "etiqueta" => "101"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            101 => array:3 [
              "identificador" => "bib1435"
              "etiqueta" => "102"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            102 => array:3 [
              "identificador" => "bib1440"
              "etiqueta" => "103"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            103 => array:3 [
              "identificador" => "bib1445"
              "etiqueta" => "104"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            104 => array:3 [
              "identificador" => "bib1450"
              "etiqueta" => "105"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            105 => array:3 [
              "identificador" => "bib1455"
              "etiqueta" => "106"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            106 => array:3 [
              "identificador" => "bib1460"
              "etiqueta" => "107"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            107 => array:3 [
              "identificador" => "bib1465"
              "etiqueta" => "108"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            108 => array:3 [
              "identificador" => "bib1470"
              "etiqueta" => "109"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            109 => array:3 [
              "identificador" => "bib1475"
              "etiqueta" => "110"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            110 => array:3 [
              "identificador" => "bib1480"
              "etiqueta" => "111"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            111 => array:3 [
              "identificador" => "bib1485"
              "etiqueta" => "112"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            112 => array:3 [
              "identificador" => "bib1490"
              "etiqueta" => "113"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            113 => array:3 [
              "identificador" => "bib1495"
              "etiqueta" => "114"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            114 => array:3 [
              "identificador" => "bib1500"
              "etiqueta" => "115"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            115 => array:3 [
              "identificador" => "bib1505"
              "etiqueta" => "116"
              "referencia" => array:1 [
                0 => array:3 [
                  "comentario" => "pii&#58;S2213-1779&#58;30535-8"
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            116 => array:3 [
              "identificador" => "bib1510"
              "etiqueta" => "117"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            117 => array:3 [
              "identificador" => "bib1515"
              "etiqueta" => "118"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            118 => array:3 [
              "identificador" => "bib1520"
              "etiqueta" => "119"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            119 => array:3 [
              "identificador" => "bib1525"
              "etiqueta" => "120"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            120 => array:3 [
              "identificador" => "bib1530"
              "etiqueta" => "121"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            121 => array:3 [
              "identificador" => "bib1535"
              "etiqueta" => "122"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            122 => array:3 [
              "identificador" => "bib1540"
              "etiqueta" => "123"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            123 => array:3 [
              "identificador" => "bib1545"
              "etiqueta" => "124"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            124 => array:3 [
              "identificador" => "bib1550"
              "etiqueta" => "125"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            125 => array:3 [
              "identificador" => "bib1555"
              "etiqueta" => "126"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            126 => array:3 [
              "identificador" => "bib1560"
              "etiqueta" => "127"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            127 => array:3 [
              "identificador" => "bib1565"
              "etiqueta" => "128"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            128 => array:3 [
              "identificador" => "bib1570"
              "etiqueta" => "129"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            129 => array:3 [
              "identificador" => "bib1575"
              "etiqueta" => "130"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            130 => array:3 [
              "identificador" => "bib1580"
              "etiqueta" => "131"
              "referencia" => array:1 [
                0 => array:3 [
                  "comentario" => "CD006423"
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            131 => array:3 [
              "identificador" => "bib1585"
              "etiqueta" => "132"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            132 => array:3 [
              "identificador" => "bib1590"
              "etiqueta" => "133"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            133 => array:3 [
              "identificador" => "bib1595"
              "etiqueta" => "134"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            134 => array:3 [
              "identificador" => "bib1600"
              "etiqueta" => "135"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            135 => array:3 [
              "identificador" => "bib1605"
              "etiqueta" => "136"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            136 => array:3 [
              "identificador" => "bib1610"
              "etiqueta" => "137"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            137 => array:3 [
              "identificador" => "bib1615"
              "etiqueta" => "138"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            138 => array:3 [
              "identificador" => "bib1620"
              "etiqueta" => "139"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            139 => array:3 [
              "identificador" => "bib1625"
              "etiqueta" => "140"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            140 => array:3 [
              "identificador" => "bib1630"
              "etiqueta" => "141"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            141 => array:3 [
              "identificador" => "bib1635"
              "etiqueta" => "142"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            142 => array:3 [
              "identificador" => "bib1640"
              "etiqueta" => "143"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            143 => array:3 [
              "identificador" => "bib1645"
              "etiqueta" => "144"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            144 => array:3 [
              "identificador" => "bib1650"
              "etiqueta" => "145"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            145 => array:3 [
              "identificador" => "bib1655"
              "etiqueta" => "146"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            146 => array:3 [
              "identificador" => "bib1660"
              "etiqueta" => "147"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            147 => array:3 [
              "identificador" => "bib1665"
              "etiqueta" => "148"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            148 => array:3 [
              "identificador" => "bib1670"
              "etiqueta" => "149"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            149 => array:3 [
              "identificador" => "bib1675"
              "etiqueta" => "150"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            150 => array:3 [
              "identificador" => "bib1680"
              "etiqueta" => "151"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            151 => array:3 [
              "identificador" => "bib1685"
              "etiqueta" => "152"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            152 => array:3 [
              "identificador" => "bib1690"
              "etiqueta" => "153"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            153 => array:3 [
              "identificador" => "bib1695"
              "etiqueta" => "154"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:1 [ …1]
                  ]
                ]
              ]
            ]
            154 => array:3 [
              "identificador" => "bib1700"
              "etiqueta" => "155"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            155 => array:3 [
              "identificador" => "bib1705"
              "etiqueta" => "156"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            156 => array:3 [
              "identificador" => "bib1710"
              "etiqueta" => "157"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            157 => array:3 [
              "identificador" => "bib1715"
              "etiqueta" => "158"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            158 => array:3 [
              "identificador" => "bib1720"
              "etiqueta" => "159"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:1 [ …1]
                  ]
                ]
              ]
            ]
            159 => array:3 [
              "identificador" => "bib1725"
              "etiqueta" => "160"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            160 => array:3 [
              "identificador" => "bib1730"
              "etiqueta" => "161"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            161 => array:3 [
              "identificador" => "bib1735"
              "etiqueta" => "162"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            162 => array:3 [
              "identificador" => "bib1740"
              "etiqueta" => "163"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            163 => array:3 [
              "identificador" => "bib1745"
              "etiqueta" => "164"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            164 => array:3 [
              "identificador" => "bib1750"
              "etiqueta" => "165"
              "referencia" => array:1 [
                0 => array:3 [
                  "comentario" => "CD005613"
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:1 [ …1]
                  ]
                ]
              ]
            ]
            165 => array:3 [
              "identificador" => "bib1755"
              "etiqueta" => "166"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            166 => array:3 [
              "identificador" => "bib1760"
              "etiqueta" => "167"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            167 => array:3 [
              "identificador" => "bib1765"
              "etiqueta" => "168"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            168 => array:3 [
              "identificador" => "bib1770"
              "etiqueta" => "169"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            169 => array:3 [
              "identificador" => "bib1775"
              "etiqueta" => "170"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            170 => array:3 [
              "identificador" => "bib1780"
              "etiqueta" => "171"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            171 => array:3 [
              "identificador" => "bib1785"
              "etiqueta" => "172"
              "referencia" => array:1 [
                0 => array:3 [
                  "comentario" => "CD003287"
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:1 [ …1]
                  ]
                ]
              ]
            ]
            172 => array:3 [
              "identificador" => "bib1790"
              "etiqueta" => "173"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            173 => array:3 [
              "identificador" => "bib1795"
              "etiqueta" => "174"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            174 => array:3 [
              "identificador" => "bib1800"
              "etiqueta" => "175"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            175 => array:3 [
              "identificador" => "bib1805"
              "etiqueta" => "176"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            176 => array:3 [
              "identificador" => "bib1810"
              "etiqueta" => "177"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:1 [ …1]
                  ]
                ]
              ]
            ]
            177 => array:3 [
              "identificador" => "bib1815"
              "etiqueta" => "178"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:1 [ …1]
                  ]
                ]
              ]
            ]
            178 => array:3 [
              "identificador" => "bib1820"
              "etiqueta" => "179"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            179 => array:3 [
              "identificador" => "bib1825"
              "etiqueta" => "180"
              "referencia" => array:1 [
                0 => array:3 [
                  "comentario" => "&#91;Epub ahead of print&#93;"
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            180 => array:3 [
              "identificador" => "bib1830"
              "etiqueta" => "181"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            181 => array:3 [
              "identificador" => "bib1835"
              "etiqueta" => "182"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            182 => array:3 [
              "identificador" => "bib1840"
              "etiqueta" => "183"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            183 => array:3 [
              "identificador" => "bib1845"
              "etiqueta" => "184"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            184 => array:3 [
              "identificador" => "bib1850"
              "etiqueta" => "185"
              "referencia" => array:1 [
                0 => array:3 [
                  "comentario" => "85e1-10"
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:1 [ …1]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/22548874/0000021800000002/v1_201802230423/S2254887418300122/v1_201802230423/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "3982"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Special Article"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/22548874/0000021800000002/v1_201802230423/S2254887418300122/v1_201802230423/en/main.pdf?idApp=WRCEE&text.app=https://revclinesp.es/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2254887418300122?idApp=WRCEE"
]
Share
Journal Information

Statistics

Follow this link to access the full text of the article

Special article
Treatment of type 2 diabetes mellitus in elderly patients
Tratamiento de la diabetes mellitus tipo 2 en el paciente anciano
R. Gómez-Huelgasa,b,c,d,
Corresponding author
ricardogomezhuelgas@hotmail.com

Corresponding author.
, F. Gómez Peraltae,f, L. Rodríguez Mañasg,h,i, F. Formigaj,k, M. Puig Domingol,m,n,ñ, J.J. Mediavilla Bravoo,p, C. Mirandaq,r, J. Enas,d
a Servicio de Medicina Interna, Hospital Regional Universitario de Málaga, Málaga, Spain
b Instituto de Investigación Biomédica de Málaga (IBIMA), Spain
c CIBER de Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Spain
d Sociedad Española de Medicina Interna (SEMI), Spain
e Unidad de Endocrinología y Nutrición, Hospital General de Segovia, Segovia, Spain
f Sociedad Española de Diabetes (SED), Spain
g Servicio de Geriatría, Hospital Universitario de Getafe, Madrid, Spain
h CIBER de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Spain
i Sociedad Española de Medicina Geriátrica (SEMEG), Spain
j Unidad de Geriatría, Hospital Universitari de Bellvitge, L¿Hospitalet de Llobregat, Barcelona, Spain
k Sociedad Española de Geriatría y Gerontología (SEGG), Spain
l Servicio de Endocrinología y Nutrición, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain
m Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, Barcelona, Spain
n CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Spain
ñ Sociedad Española de Endocrinología y Nutrición (SEEN), Spain
o Centro de Salud Burgos Rural, Burgos, Spain
p Sociedad Española de Medicina General (SEMERGEN), Spain
q Centro de Salud Buenavista, Toledo, Spain
r Sociedad Española de Médicos Generales y de Familia (SEMG), Spain
s Servicio de Medicina Interna, Hospital Marina Baixa, La Vila Joiosa, Alicante, Spain
Ver más
Read
1335
Times
was read the article
91
Total PDF
1244
Total HTML
Share statistics
 array:24 [
  "pii" => "S2254887418300122"
  "issn" => "22548874"
  "doi" => "10.1016/j.rceng.2017.12.004"
  "estado" => "S300"
  "fechaPublicacion" => "2018-03-01"
  "aid" => "1457"
  "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46; and Sociedad Espa&#241;ola de Medicina Interna &#40;SEMI&#41;"
  "copyrightAnyo" => "2017"
  "documento" => "article"
  "crossmark" => 1
  "subdocumento" => "fla"
  "cita" => "Rev Clin Esp. 2018;218:74-88"
  "abierto" => array:3 [
    "ES" => false
    "ES2" => false
    "LATM" => false
  ]
  "gratuito" => false
  "lecturas" => array:2 [
    "total" => 9
    "formatos" => array:2 [
      "HTML" => 5
      "PDF" => 4
    ]
  ]
  "Traduccion" => array:1 [
    "es" => array:19 [
      "pii" => "S0014256517302886"
      "issn" => "00142565"
      "doi" => "10.1016/j.rce.2017.12.003"
      "estado" => "S300"
      "fechaPublicacion" => "2018-03-01"
      "aid" => "1457"
      "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46; and Sociedad Espa&#241;ola de Medicina Interna &#40;SEMI&#41;"
      "documento" => "article"
      "crossmark" => 1
      "subdocumento" => "fla"
      "cita" => "Rev Clin Esp. 2018;218:74-88"
      "abierto" => array:3 [
        "ES" => false
        "ES2" => false
        "LATM" => false
      ]
      "gratuito" => false
      "lecturas" => array:2 [
        "total" => 380
        "formatos" => array:2 [
          "HTML" => 226
          "PDF" => 154
        ]
      ]
      "es" => array:13 [
        "idiomaDefecto" => true
        "cabecera" => "<span class="elsevierStyleTextfn">ART&#205;CULO ESPECIAL</span>"
        "titulo" => "Tratamiento de la diabetes mellitus tipo 2 en el paciente anciano"
        "tienePdf" => "es"
        "tieneTextoCompleto" => "es"
        "tieneResumen" => array:2 [
          0 => "es"
          1 => "en"
        ]
        "paginas" => array:1 [
          0 => array:2 [
            "paginaInicial" => "74"
            "paginaFinal" => "88"
          ]
        ]
        "titulosAlternativos" => array:1 [
          "en" => array:1 [
            "titulo" => "Treatment of type 2 diabetes mellitus in elderly patients"
          ]
        ]
        "contieneResumen" => array:2 [
          "es" => true
          "en" => true
        ]
        "contieneTextoCompleto" => array:1 [
          "es" => true
        ]
        "contienePdf" => array:1 [
          "es" => true
        ]
        "resumenGrafico" => array:2 [
          "original" => 0
          "multimedia" => array:7 [
            "identificador" => "fig0005"
            "etiqueta" => "Figura 1"
            "tipo" => "MULTIMEDIAFIGURA"
            "mostrarFloat" => true
            "mostrarDisplay" => false
            "figura" => array:1 [
              0 => array:4 [
                "imagen" => "gr1.jpeg"
                "Alto" => 1478
                "Ancho" => 2506
                "Tamanyo" => 264090
              ]
            ]
            "descripcion" => array:1 [
              "es" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Algoritmo del tratamiento de la diabetes mellitus tipo2 en el paciente anciano&#46;</p> <p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">arGLP1&#58; agonistas del receptor del <span class="elsevierStyleItalic">glucagon-like peptide-1&#59;</span> iDPP4&#58; inhibidores de la dipeptidil peptidasa-4&#59; iSGLT2&#58; inhibidores del cotransportador sodio-glucosa tipo 2&#46;</p> <p id="spar0035" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">a</span> Repaglinida y pioglitazona pueden emplearse en pacientes con FG &#60; 30 ml&#47;min&#44; pero su uso no es recomendable por el riesgo de efectos adversos&#58; hipoglucemias &#40;repaglinida&#41;&#59; retenci&#243;n hidrosalina&#44; insuficiencia cardiaca y fracturas &#40;pioglitazona&#41;&#46;</p> <p id="spar0040" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">b</span> Empagliflozina&#44; canagliflozina y liraglutida han demostrado reducci&#243;n de la morbimortalidad cardiovascular en pacientes con diabetes tipo 2 de alto riesgo vascular&#46;</p> <p id="spar0045" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">c</span> Saxagliptina deben evitarse en pacientes con insuficiencia cardiaca&#46;</p> <p id="spar0050" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">d</span> Pioglitazona est&#225; contraindicada en pacientes con insuficiencia cardiaca o en riesgo de fracturas&#46;</p>"
            ]
          ]
        ]
        "autores" => array:1 [
          0 => array:2 [
            "autoresLista" => "R&#46; G&#243;mez-Huelgas, F&#46; G&#243;mez Peralta, L&#46; Rodr&#237;guez Ma&#241;as, F&#46; Formiga, M&#46; Puig Domingo, J&#46;J&#46; Mediavilla Bravo, C&#46; Miranda, J&#46; Ena"
            "autores" => array:8 [
              0 => array:2 [
                "nombre" => "R&#46;"
                "apellidos" => "G&#243;mez-Huelgas"
              ]
              1 => array:2 [
                "nombre" => "F&#46;"
                "apellidos" => "G&#243;mez Peralta"
              ]
              2 => array:2 [
                "nombre" => "L&#46;"
                "apellidos" => "Rodr&#237;guez Ma&#241;as"
              ]
              3 => array:2 [
                "nombre" => "F&#46;"
                "apellidos" => "Formiga"
              ]
              4 => array:2 [
                "nombre" => "M&#46;"
                "apellidos" => "Puig Domingo"
              ]
              5 => array:2 [
                "nombre" => "J&#46;J&#46;"
                "apellidos" => "Mediavilla Bravo"
              ]
              6 => array:2 [
                "nombre" => "C&#46;"
                "apellidos" => "Miranda"
              ]
              7 => array:2 [
                "nombre" => "J&#46;"
                "apellidos" => "Ena"
              ]
            ]
          ]
        ]
      ]
      "idiomaDefecto" => "es"
      "Traduccion" => array:1 [
        "en" => array:9 [
          "pii" => "S2254887418300122"
          "doi" => "10.1016/j.rceng.2017.12.004"
          "estado" => "S300"
          "subdocumento" => ""
          "abierto" => array:3 [
            "ES" => false
            "ES2" => false
            "LATM" => false
          ]
          "gratuito" => false
          "lecturas" => array:1 [
            "total" => 0
          ]
          "idiomaDefecto" => "en"
          "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2254887418300122?idApp=WRCEE"
        ]
      ]
      "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0014256517302886?idApp=WRCEE"
      "url" => "/00142565/0000021800000002/v1_201802240414/S0014256517302886/v1_201802240414/es/main.assets"
    ]
  ]
  "itemSiguiente" => array:19 [
    "pii" => "S2254887417301376"
    "issn" => "22548874"
    "doi" => "10.1016/j.rceng.2017.11.001"
    "estado" => "S300"
    "fechaPublicacion" => "2018-03-01"
    "aid" => "1450"
    "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46; and Sociedad Espa&#241;ola de Medicina Interna &#40;SEMI&#41;"
    "documento" => "article"
    "crossmark" => 1
    "subdocumento" => "ssu"
    "cita" => "Rev Clin Esp. 2018;218:89-97"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:2 [
      "total" => 2
      "PDF" => 2
    ]
    "en" => array:13 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Review</span>"
      "titulo" => "Characteristics of patients with myelomatous pleural effusion&#46; A systematic review"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "es"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "89"
          "paginaFinal" => "97"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Caracter&#237;sticas de los pacientes con derrame pleural mielomatoso&#46; Revisi&#243;n sistem&#225;tica"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "es" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig0005"
          "etiqueta" => "Figure 1"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr1.jpeg"
              "Alto" => 1672
              "Ancho" => 2667
              "Tamanyo" => 218564
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">PRISMA flow diagram of the reviewed literature&#46; Abbreviation&#58; PRISMA&#44; Preferred Reporting Items for Systematic reviews and Meta-Analyses&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "V&#46; Riveiro, L&#46; Ferreiro, M&#46;E&#46; Toubes, A&#46; Lama, J&#46;M&#46; &#193;lvarez-Doba&#241;o, L&#46; Vald&#233;s"
          "autores" => array:6 [
            0 => array:2 [
              "nombre" => "V&#46;"
              "apellidos" => "Riveiro"
            ]
            1 => array:2 [
              "nombre" => "L&#46;"
              "apellidos" => "Ferreiro"
            ]
            2 => array:2 [
              "nombre" => "M&#46;E&#46;"
              "apellidos" => "Toubes"
            ]
            3 => array:2 [
              "nombre" => "A&#46;"
              "apellidos" => "Lama"
            ]
            4 => array:2 [
              "nombre" => "J&#46;M&#46;"
              "apellidos" => "&#193;lvarez-Doba&#241;o"
            ]
            5 => array:2 [
              "nombre" => "L&#46;"
              "apellidos" => "Vald&#233;s"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "es" => array:9 [
        "pii" => "S0014256517302618"
        "doi" => "10.1016/j.rce.2017.11.001"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => false
          "ES2" => false
          "LATM" => false
        ]
        "gratuito" => false
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "es"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0014256517302618?idApp=WRCEE"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2254887417301376?idApp=WRCEE"
    "url" => "/22548874/0000021800000002/v1_201802230423/S2254887417301376/v1_201802230423/en/main.assets"
  ]
  "itemAnterior" => array:19 [
    "pii" => "S2254887418300249"
    "issn" => "22548874"
    "doi" => "10.1016/j.rceng.2018.01.003"
    "estado" => "S300"
    "fechaPublicacion" => "2018-03-01"
    "aid" => "1466"
    "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46; and Sociedad Espa&#241;ola de Medicina Interna &#40;SEMI&#41;"
    "documento" => "simple-article"
    "crossmark" => 1
    "subdocumento" => "edi"
    "cita" => "Rev Clin Esp. 2018;218:72-3"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:2 [
      "total" => 1
      "PDF" => 1
    ]
    "en" => array:10 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Editorial</span>"
      "titulo" => "Clinical scales&#58; Tools for the diagnosis of unstable angina"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "72"
          "paginaFinal" => "73"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Escalas cl&#237;nicas&#58; una herramienta para el diagn&#243;stico de angina inestable"
        ]
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "A&#46; Alqu&#233;zar-Arb&#233;, B&#46; Lopez Barbeito"
          "autores" => array:2 [
            0 => array:2 [
              "nombre" => "A&#46;"
              "apellidos" => "Alqu&#233;zar-Arb&#233;"
            ]
            1 => array:2 [
              "nombre" => "B&#46;"
              "apellidos" => "Lopez Barbeito"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "es" => array:9 [
        "pii" => "S0014256518300250"
        "doi" => "10.1016/j.rce.2018.01.005"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => false
          "ES2" => false
          "LATM" => false
        ]
        "gratuito" => false
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "es"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0014256518300250?idApp=WRCEE"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2254887418300249?idApp=WRCEE"
    "url" => "/22548874/0000021800000002/v1_201802230423/S2254887418300249/v1_201802230423/en/main.assets"
  ]
  "en" => array:20 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Special article</span>"
    "titulo" => "Treatment of type 2 diabetes mellitus in elderly patients"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "74"
        "paginaFinal" => "88"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "R&#46; G&#243;mez-Huelgas, F&#46; G&#243;mez Peralta, L&#46; Rodr&#237;guez Ma&#241;as, F&#46; Formiga, M&#46; Puig Domingo, J&#46;J&#46; Mediavilla Bravo, C&#46; Miranda, J&#46; Ena"
        "autores" => array:8 [
          0 => array:4 [
            "nombre" => "R&#46;"
            "apellidos" => "G&#243;mez-Huelgas"
            "email" => array:1 [
              0 => "ricardogomezhuelgas&#64;hotmail&#46;com"
            ]
            "referencia" => array:5 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
              2 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">c</span>"
                "identificador" => "aff0015"
              ]
              3 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">d</span>"
                "identificador" => "aff0020"
              ]
              4 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "F&#46;"
            "apellidos" => "G&#243;mez Peralta"
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">e</span>"
                "identificador" => "aff0025"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">f</span>"
                "identificador" => "aff0030"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "L&#46;"
            "apellidos" => "Rodr&#237;guez Ma&#241;as"
            "referencia" => array:3 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">g</span>"
                "identificador" => "aff0035"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">h</span>"
                "identificador" => "aff0040"
              ]
              2 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">i</span>"
                "identificador" => "aff0045"
              ]
            ]
          ]
          3 => array:3 [
            "nombre" => "F&#46;"
            "apellidos" => "Formiga"
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">j</span>"
                "identificador" => "aff0050"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">k</span>"
                "identificador" => "aff0055"
              ]
            ]
          ]
          4 => array:3 [
            "nombre" => "M&#46;"
            "apellidos" => "Puig Domingo"
            "referencia" => array:4 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">l</span>"
                "identificador" => "aff0060"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">m</span>"
                "identificador" => "aff0065"
              ]
              2 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">n</span>"
                "identificador" => "aff0070"
              ]
              3 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#241;</span>"
                "identificador" => "aff0075"
              ]
            ]
          ]
          5 => array:3 [
            "nombre" => "J&#46;J&#46;"
            "apellidos" => "Mediavilla Bravo"
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">o</span>"
                "identificador" => "aff0080"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">p</span>"
                "identificador" => "aff0085"
              ]
            ]
          ]
          6 => array:3 [
            "nombre" => "C&#46;"
            "apellidos" => "Miranda"
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">q</span>"
                "identificador" => "aff0090"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">r</span>"
                "identificador" => "aff0095"
              ]
            ]
          ]
          7 => array:3 [
            "nombre" => "J&#46;"
            "apellidos" => "Ena"
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">s</span>"
                "identificador" => "aff0100"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">d</span>"
                "identificador" => "aff0020"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:20 [
          0 => array:3 [
            "entidad" => "Servicio de Medicina Interna&#44; Hospital Regional Universitario de M&#225;laga&#44; M&#225;laga&#44; Spain"
            "etiqueta" => "a"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "Instituto de Investigaci&#243;n Biom&#233;dica de M&#225;laga &#40;IBIMA&#41;&#44; Spain"
            "etiqueta" => "b"
            "identificador" => "aff0010"
          ]
          2 => array:3 [
            "entidad" => "CIBER de Obesidad y Nutrici&#243;n &#40;CIBEROBN&#41;&#44; Instituto de Salud Carlos III&#44; Spain"
            "etiqueta" => "c"
            "identificador" => "aff0015"
          ]
          3 => array:3 [
            "entidad" => "Sociedad Espa&#241;ola de Medicina Interna &#40;SEMI&#41;&#44; Spain"
            "etiqueta" => "d"
            "identificador" => "aff0020"
          ]
          4 => array:3 [
            "entidad" => "Unidad de Endocrinolog&#237;a y Nutrici&#243;n&#44; Hospital General de Segovia&#44; Segovia&#44; Spain"
            "etiqueta" => "e"
            "identificador" => "aff0025"
          ]
          5 => array:3 [
            "entidad" => "Sociedad Espa&#241;ola de Diabetes &#40;SED&#41;&#44; Spain"
            "etiqueta" => "f"
            "identificador" => "aff0030"
          ]
          6 => array:3 [
            "entidad" => "Servicio de Geriatr&#237;a&#44; Hospital Universitario de Getafe&#44; Madrid&#44; Spain"
            "etiqueta" => "g"
            "identificador" => "aff0035"
          ]
          7 => array:3 [
            "entidad" => "CIBER de Fragilidad y Envejecimiento Saludable &#40;CIBERFES&#41;&#44; Instituto de Salud Carlos III&#44; Spain"
            "etiqueta" => "h"
            "identificador" => "aff0040"
          ]
          8 => array:3 [
            "entidad" => "Sociedad Espa&#241;ola de Medicina Geri&#225;trica &#40;SEMEG&#41;&#44; Spain"
            "etiqueta" => "i"
            "identificador" => "aff0045"
          ]
          9 => array:3 [
            "entidad" => "Unidad de Geriatr&#237;a&#44; Hospital Universitari de Bellvitge&#44; L¿Hospitalet de Llobregat&#44; Barcelona&#44; Spain"
            "etiqueta" => "j"
            "identificador" => "aff0050"
          ]
          10 => array:3 [
            "entidad" => "Sociedad Espa&#241;ola de Geriatr&#237;a y Gerontolog&#237;a &#40;SEGG&#41;&#44; Spain"
            "etiqueta" => "k"
            "identificador" => "aff0055"
          ]
          11 => array:3 [
            "entidad" => "Servicio de Endocrinolog&#237;a y Nutrici&#243;n&#44; Hospital Germans Trias i Pujol&#44; Badalona&#44; Barcelona&#44; Spain"
            "etiqueta" => "l"
            "identificador" => "aff0060"
          ]
          12 => array:3 [
            "entidad" => "Institut d&#8217;Investigaci&#243; en Ci&#232;ncies de la Salut Germans Trias i Pujol&#44; Badalona&#44; Barcelona&#44; Spain"
            "etiqueta" => "m"
            "identificador" => "aff0065"
          ]
          13 => array:3 [
            "entidad" => "CIBER de Diabetes y Enfermedades Metab&#243;licas Asociadas &#40;CIBERDEM&#41;&#44; Instituto de Salud Carlos III&#44; Spain"
            "etiqueta" => "n"
            "identificador" => "aff0070"
          ]
          14 => array:3 [
            "entidad" => "Sociedad Espa&#241;ola de Endocrinolog&#237;a y Nutrici&#243;n &#40;SEEN&#41;&#44; Spain"
            "etiqueta" => "&#241;"
            "identificador" => "aff0075"
          ]
          15 => array:3 [
            "entidad" => "Centro de Salud Burgos Rural&#44; Burgos&#44; Spain"
            "etiqueta" => "o"
            "identificador" => "aff0080"
          ]
          16 => array:3 [
            "entidad" => "Sociedad Espa&#241;ola de Medicina General &#40;SEMERGEN&#41;&#44; Spain"
            "etiqueta" => "p"
            "identificador" => "aff0085"
          ]
          17 => array:3 [
            "entidad" => "Centro de Salud Buenavista&#44; Toledo&#44; Spain"
            "etiqueta" => "q"
            "identificador" => "aff0090"
          ]
          18 => array:3 [
            "entidad" => "Sociedad Espa&#241;ola de M&#233;dicos Generales y de Familia &#40;SEMG&#41;&#44; Spain"
            "etiqueta" => "r"
            "identificador" => "aff0095"
          ]
          19 => array:3 [
            "entidad" => "Servicio de Medicina Interna&#44; Hospital Marina Baixa&#44; La Vila Joiosa&#44; Alicante&#44; Spain"
            "etiqueta" => "s"
            "identificador" => "aff0100"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Corresponding author&#46;"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "Tratamiento de la diabetes mellitus tipo 2 en el paciente anciano"
      ]
    ]
    "resumenGrafico" => array:2 [
      "original" => 0
      "multimedia" => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1519
            "Ancho" => 2506
            "Tamanyo" => 258442
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Treatment algorithm for type 2 diabetes mellitus in elderly patients&#46;</p> <p id="spar0020" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; DPP4i&#58; dipeptidyl peptidase-4 inhibitors&#59; GLP-1RA&#58; glucagon-like peptide-1 receptor agonists&#59; SGLT2i&#58; sodium-glucose cotransporter 2 inhibitors&#46;</p> <p id="spar0025" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">a</span> Repaglinide and pioglitazone can be used in patients with GFR &#60;30<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#44; but their use is not recommended due to the risk of adverse effects&#58; hypoglycemia &#40;repaglinide&#41;&#59; salt and fluid retention&#44; heart failure and fractures &#40;pioglitazone&#41;&#46;</p> <p id="spar0030" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">b</span> Empagliflozin&#44; canagliflozin and liraglutide have shown reduced cardiovascular morbidity and mortality in patients with high vascular risk type 2 diabetes&#46;</p> <p id="spar0035" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">c</span> Saxagliptin should be avoided for patients with heart failure&#46;</p> <p id="spar0040" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">d</span> Pioglitazone is contraindicated for patients with heart failure or at risk for fractures&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Background</span><p id="par0005" class="elsevierStylePara elsevierViewall">Aging is characterized by a progressive loss of an individual&#39;s functional capacity&#46; The elderly population is biologically heterogeneous&#44; thereby necessitating a comprehensive assessment&#44; one that includes functional aspects in the decision-making process&#46;<a class="elsevierStyleCrossRef" href="#bib0930"><span class="elsevierStyleSup">1</span></a> Although there is no consensus on the definition of an individual as elderly&#44; this document uses the operational definition of having an age greater than 75 years or presenting frailty&#46;<a class="elsevierStyleCrossRef" href="#bib0935"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Demographic predictions put Spain as one of the most aged countries in the world&#46; In 2050&#44; 12&#37; of the Spanish population will be 80 years of age or older&#46;<a class="elsevierStyleCrossRef" href="#bib0940"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Type 2 diabetes mellitus &#40;DM2&#41; is a disease closely linked to aging&#44; and its prevalence increases markedly with age&#46; This situation is due to the combination of insulin secretion deficiency&#44; insulin resistance &#40;related to the increase in visceral&#44; intermuscular and intramuscular adiposity&#41;&#44; sarcopenia and physical inactivity in elderly patients&#46; In Spain&#44; 63&#37; of patients with diabetes &#40;of whom more than 90&#37; have DM2&#41; are older than 65 years&#44;<a class="elsevierStyleCrossRef" href="#bib0945"><span class="elsevierStyleSup">4</span></a> and more than a third of the population older than 75 years has diabetes&#46;<a class="elsevierStyleCrossRef" href="#bib0950"><span class="elsevierStyleSup">5</span></a> It has been predicted that the number of patients with diabetes older than 70 years will quadruple worldwide in the next 3 decades due to the increase in DM2&#46;<a class="elsevierStyleCrossRef" href="#bib0955"><span class="elsevierStyleSup">6</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Antidiabetic treatment and the objectives of glycemic control in elderly patients with DM2 should be individualized according to their biopsychosocial characteristics&#46; In elderly patients for whom the benefits of intensive antidiabetic treatment are limited&#44; the basic objectives should be to improve the quality of life&#44; preserve functionality and prevent adverse effects&#44; especially hypoglycemia&#46;<a class="elsevierStyleCrossRef" href="#bib0960"><span class="elsevierStyleSup">7</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Treatment of DM2 in the elderly was the subject of a consensus document published in 2012 and endorsed by several Spanish scientific societies&#46;<a class="elsevierStyleCrossRef" href="#bib0965"><span class="elsevierStyleSup">8</span></a> Since then&#44; new therapeutic groups and evidence have emerged that warrant an update to this consensus document&#46; The present document focuses on the therapeutic aspects of DM2 in elderly patients&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Functional capacity&#44; frailty and diabetes</span><p id="par0030" class="elsevierStylePara elsevierViewall">Frailty is a clinical syndrome associated with aging&#44; characterized by the presence of at least 3 of the following criteria&#58; involuntary weight loss&#44; exhaustion&#44; muscle weakness&#44; slowness of gait and physical hypoactivity &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0935"><span class="elsevierStyleSup">2</span></a> Frailty is the main predictor of disability&#44; dependence and mortality in the elderly&#44;<a class="elsevierStyleCrossRef" href="#bib0970"><span class="elsevierStyleSup">9</span></a> including those with diabetes&#44;<a class="elsevierStyleCrossRef" href="#bib0975"><span class="elsevierStyleSup">10</span></a> and is a more potent prognostic marker than the comorbidity burden&#46;<a class="elsevierStyleCrossRef" href="#bib0980"><span class="elsevierStyleSup">11</span></a> Diabetes is a risk factor for the development of frailty&#44;<a class="elsevierStyleCrossRef" href="#bib0985"><span class="elsevierStyleSup">12</span></a> both for predisposing patients to sarcopenia and cognitive dysfunction and for microvascular and macrovascular complications &#40;retinopathy&#44; polyneuropathy&#44; dysautonomia&#44; renal failure and cardiovascular disease&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0930"><span class="elsevierStyleSup">1</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">Early detection of frailty and sarcopenia are key aspects in the management of elderly patients in general<a class="elsevierStyleCrossRefs" href="#bib0990"><span class="elsevierStyleSup">13&#44;14</span></a> and in those who have diabetes in particular&#46;<a class="elsevierStyleCrossRef" href="#bib0930"><span class="elsevierStyleSup">1</span></a> The objectives of glycemic control should be based on the patient&#39;s functional status&#44; because neither frail elderly patients nor those with established functional impairment will benefit from strict glycemic control&#44;<a class="elsevierStyleCrossRef" href="#bib1000"><span class="elsevierStyleSup">15</span></a> which can simultaneously increase the risk of hypoglycemia&#46;<a class="elsevierStyleCrossRef" href="#bib1005"><span class="elsevierStyleSup">16</span></a> A recent study concluded that the degree of glycemic control in institutionalized elderly patients was not related to persistent functional impairment or death&#44; which highlighted the need to be conservative when managing diabetes in this population&#46;<a class="elsevierStyleCrossRef" href="#bib1010"><span class="elsevierStyleSup">17</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The early implementation of multimodal and multidisciplinary interventions in elderly patients with DM2&#44; based on nutritional education and promoting physical activity&#44; has been shown effective for maintaining functional autonomy&#46;<a class="elsevierStyleCrossRef" href="#bib1015"><span class="elsevierStyleSup">18</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Hypoglycemia in elderly patients</span><p id="par0045" class="elsevierStylePara elsevierViewall">The risk of severe hypoglycemia increases exponentially with age&#46; A recent epidemiological study&#44; performed on a Spanish population&#44; reported that more than two-thirds of cases of severe hypoglycemia treated in emergency departments occurred in individuals older than 60 years&#44; and 46&#37; occurred in those older than 76 years&#46;<a class="elsevierStyleCrossRef" href="#bib1020"><span class="elsevierStyleSup">19</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">In Spain&#44; the mean age of patients with diabetes hospitalized for severe hypoglycemia exceeded 70 years&#46;<a class="elsevierStyleCrossRef" href="#bib1025"><span class="elsevierStyleSup">20</span></a> Even so&#44; overtreatment of hyperglycemia remains the rule&#44; as demonstrated by published data from the United States<a class="elsevierStyleCrossRef" href="#bib1030"><span class="elsevierStyleSup">21</span></a> and Spain&#46;<a class="elsevierStyleCrossRef" href="#bib1035"><span class="elsevierStyleSup">22</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Elderly patients are more exposed to polypharmacy&#44; drug interactions and adverse drug effects&#46; Hypoglycemia secondary to the use of antidiabetic agents &#40;insulin&#44; sulfonylureas&#41; represents the second leading cause of hospitalization in emergency departments due to adverse drug effects&#46;<a class="elsevierStyleCrossRef" href="#bib1040"><span class="elsevierStyleSup">23</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">The higher rate of severe hypoglycemia is partly explained by the fact that&#44; due to the lack of adrenergic alarm symptoms&#44; asymptomatic hypoglycemia is more common in the elderly&#44;<a class="elsevierStyleCrossRef" href="#bib1045"><span class="elsevierStyleSup">24</span></a> even in those who have poor glycemic control&#46;<a class="elsevierStyleCrossRef" href="#bib1050"><span class="elsevierStyleSup">25</span></a> Elderly patients with cognitive disorder are a special risk group for severe hypoglycemia&#46;<a class="elsevierStyleCrossRef" href="#bib1055"><span class="elsevierStyleSup">26</span></a> Hypoglycemia in the elderly is associated with delirium&#44; cognitive impairment&#44; falls and fractures&#44; stroke&#44; cardiac arrhythmia and increased mortality&#46;<a class="elsevierStyleCrossRefs" href="#bib1060"><span class="elsevierStyleSup">27&#8211;29</span></a> Preventing hypoglycemia should therefore be a therapeutic priority&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">As a general rule for elderly patients&#44; it is recommended that treatment be started with antidiabetic agents with low hypoglycemic risk &#40;especially metformin and dipeptidyl peptidase-4 inhibitors &#91;DPP-4i&#93;&#41; at low doses&#44; with a progressive increase in dose&#44; monitoring the response after each increase&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1075"><span class="elsevierStyleSup">30</span></a> As much as possible&#44; drugs associated with a high risk of hypoglycemia &#40;sulfonylureas and insulin&#44; especially prandial and mixtures&#41; should be avoided&#46;<a class="elsevierStyleCrossRef" href="#bib0965"><span class="elsevierStyleSup">8</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">General principles in the treatment of elderly patients with type 2 diabetes</span><p id="par0070" class="elsevierStylePara elsevierViewall">The general principles that should govern the treatment of elderly patients with DM2 are as follows&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1&#46;</span><p id="par0075" class="elsevierStylePara elsevierViewall">The therapeutic plan and glycemic control objectives should be based on a comprehensive patient assessment that accounts for the comorbidities&#44; functional and cognitive capacity&#44; affective disorders &#40;with special emphasis on depressive conditions&#41; and social support&#44; which together help estimate the patient&#39;s total and active life expectancy&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2&#46;</span><p id="par0080" class="elsevierStylePara elsevierViewall">It is essential to establish a shared decision-making process with the patient and their caregiver&#40;s&#41; that includes their wishes&#44; expectations&#44; preferences and capabilities&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">3&#46;</span><p id="par0085" class="elsevierStylePara elsevierViewall">The antidiabetic treatment objectives should be to preserve functional capacity and improve the quality of life&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">4&#46;</span><p id="par0090" class="elsevierStylePara elsevierViewall">Special attention should be paid to the contraindications&#44; adverse effects and potential drug interactions of antidiabetic drugs&#46;</p></li></ul></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Glycemic control objectives for elderly patients</span><p id="par0095" class="elsevierStylePara elsevierViewall">The glycemic control objectives for elderly patients should be adapted to the patients&#8217; functional and cognitive status&#44; comorbidities and life expectancy&#46;<a class="elsevierStyleCrossRef" href="#bib0965"><span class="elsevierStyleSup">8</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">Based on the individual assessment&#44; 3 possibilities should be considered&#58; 1&#41; healthy elderly individuals with good functional and cognitive status&#44; low comorbidity burden and good life expectancy&#58; the therapeutic interventions and objectives may be similar to those of young adults with diabetes &#40;HbA1c&#44; 7&#8211;7&#46;5&#37;&#41;<a class="elsevierStyleCrossRef" href="#bib1080"><span class="elsevierStyleSup">31</span></a>&#59; 2&#41; frail elderly with functional disability&#44; dementia and&#47;or limited life expectancy&#58; Symptomatic hypoglycemia and hyperglycemia should be prevented&#46; A reasonable objective would be to maintain an HbA1c level of 7&#46;5&#8211;8&#46;5&#37;<a class="elsevierStyleCrossRefs" href="#bib0965"><span class="elsevierStyleSup">8&#44;32</span></a>&#59; and 3&#41; elderly patients undergoing palliative care&#58; The priority should be to preserve the quality of life&#44; prevent symptomatic hyperglycemia and hypoglycemia and reduce the burden associated with antidiabetic treatment&#46; In this context&#44; measuring HbA1c is not relevant&#46; Blood sugar should be kept below the renal threshold for glucose &#40;&#60;200<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#41;&#46; The treatment should be simplified&#44; avoiding drugs that induce hypoglycemia and those associated with gastrointestinal symptoms and hyporexia&#46; Prandial insulin can be discontinued or substituted by oral drugs&#46; The number of capillary blood sugar checks should be decreased or even eliminated&#46;<a class="elsevierStyleCrossRef" href="#bib1090"><span class="elsevierStyleSup">33</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Nonpharmacological treatment&#58; nutrition and physical activity</span><p id="par0105" class="elsevierStylePara elsevierViewall">There is little evidence of the benefits of lifestyle changes &#40;therapeutic education&#44; nutrition counseling&#44; individualized physical activity&#41; for elderly or frail patients with DM2&#46;<a class="elsevierStyleCrossRef" href="#bib1080"><span class="elsevierStyleSup">31</span></a> A study is currently underway to analyze the impact of lifestyle changes on the functional capacity and quality of life of frail and &#8220;prefrail&#8221; elderly patients with DM2&#46;<a class="elsevierStyleCrossRef" href="#bib1095"><span class="elsevierStyleSup">34</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">The Look AHEAD study included patients younger than 75 years &#40;mean age&#44; 59 years&#41; with DM2 and obesity and found that although an intensive multifactorial intervention aimed at weight loss did not manage to reduce cardiovascular events&#44;<a class="elsevierStyleCrossRef" href="#bib1100"><span class="elsevierStyleSup">35</span></a> it did improve the achievement of the objectives of metabolic control&#44; cardiovascular risk factors&#44; functional status and quality of life&#46;<a class="elsevierStyleCrossRef" href="#bib1105"><span class="elsevierStyleSup">36</span></a> This benefit was greater in the older subgroup &#40;65&#8211;75 years&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1110"><span class="elsevierStyleSup">37</span></a> Nutrition education programs have shown improved metabolic control in the elderly&#46;<a class="elsevierStyleCrossRef" href="#bib1115"><span class="elsevierStyleSup">38</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Excessively low-calorie diets should be avoided in elderly patients due to increased risk of hypoglycemia and malnutrition&#44; as these diets typically provide few proteins&#46; This fact is important because sarcopenic obesity is frequent in the elderly and is characterized by a high body mass index &#40;BMI&#41; and low muscle mass&#46; Highly restrictive diets can therefore worsen sarcopenia&#44; which is associated with functional impairment&#44; a risk of falls and institutionalization&#46;<a class="elsevierStyleCrossRefs" href="#bib1120"><span class="elsevierStyleSup">39&#44;40</span></a> Elderly patients might also need calcium and vitamin D and B12 supplements&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">The elderly are often believed not to benefit from variable-intensity physical exercise programs&#44; not being able to perform them or not having good adherence&#46; However&#44; physical activity&#44; especially multicomponent activity &#40;aerobic&#44; resistance&#44; flexibility and balance&#41;&#44; has shown its efficacy in the elderly with diabetes&#44; improving not only glycemic control but also functional independence&#44; self-esteem and quality of life&#46; Its practice should therefore be recommended&#46;<a class="elsevierStyleCrossRef" href="#bib1130"><span class="elsevierStyleSup">41</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">The prescription of physical activity should be adapted to the patient&#39;s limitations and preferences&#46; Before implementing a physical activity program&#44; the presence of potential contraindications&#44; geriatric syndromes and limitations resulting from drug treatment should be ruled out&#46; When starting a program&#44; it is important to prevent orthostatic hypotension&#44; dehydration and hypoglycemia &#40;especially in patients treated with insulin or secretagogues&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1130"><span class="elsevierStyleSup">41</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">Aerobic activities should be preferably indicated&#44; although they are often limited by the associated comorbidity &#40;e&#46;g&#46;&#44; cardiovascular and muscle-skeletal diseases&#41;&#46; Aerobic exercises prevent falls&#44; sarcopenia and functional impairment in patients with diabetes<a class="elsevierStyleCrossRef" href="#bib1135"><span class="elsevierStyleSup">42</span></a> and improves the cardiovascular risk profile&#46;<a class="elsevierStyleCrossRef" href="#bib1140"><span class="elsevierStyleSup">43</span></a> Even a simple program of regular strolls decreases glycemia under fasting conditions&#44; HbA1c and triglyceride levels in elderly patients with DM2&#46;<a class="elsevierStyleCrossRef" href="#bib1145"><span class="elsevierStyleSup">44</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">Resistance training to increase muscle mass is considered an essential component for preventing and treating DM2 in the elderly and is the program of choice for frail elderly patients&#46; Moderate to high-intensity exercises are&#44; in contrast to previous assumptions&#44; more effective for glycemic control and are generally safe for the elderly population&#46; Exercises reaching 60&#8211;70&#37; of the maximum load are usually considered sufficient &#40;in weight training&#44; the maximum weight that can be lifted in a certain exercise to perform one repetition is called a one-repetition maximum&#41;&#46; Resistance training has shown metabolic benefits in elderly patients with DM2 &#40;improved insulin sensitivity&#44; reduced blood glucose under fasting conditions and reduced visceral adiposity&#41;<a class="elsevierStyleCrossRef" href="#bib1150"><span class="elsevierStyleSup">45</span></a> and is associated with improved muscle strength and mobility and reduced falls&#46;<a class="elsevierStyleCrossRef" href="#bib1155"><span class="elsevierStyleSup">46</span></a> However&#44; to maintain the benefits of resistance training&#44; continuous supervision is usually required&#46;<a class="elsevierStyleCrossRef" href="#bib1160"><span class="elsevierStyleSup">47</span></a> Lastly&#44; balance training reduces falls in the elderly with DM2&#46;<a class="elsevierStyleCrossRef" href="#bib1165"><span class="elsevierStyleSup">48</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Pharmacotherapy</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Metformin</span><p id="par0140" class="elsevierStylePara elsevierViewall">Although no specific clinical trials have evaluated the safety and efficacy of metformin in the elderly&#44; clinical experience supports its use as the basis of DM2 therapy in any age group&#44;<a class="elsevierStyleCrossRefs" href="#bib1170"><span class="elsevierStyleSup">49&#8211;51</span></a> especially for patients with a high BMI&#44;<a class="elsevierStyleCrossRef" href="#bib1185"><span class="elsevierStyleSup">52</span></a> although it is also effective in those with normal weight&#46; Metformin acts through numerous mechanisms&#44; although the main mechanism appears to be the activation of adenosine monophosphate-kinase&#44; which leads to a reduction in the release of glucose by the liver&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Metformin does not usually cause hypoglycemia and has been shown to be useful in patients with cardiovascular disease or stable heart failure&#46;<a class="elsevierStyleCrossRef" href="#bib1190"><span class="elsevierStyleSup">53</span></a> Nevertheless&#44; the use of metformin in the elderly can be associated with adverse events such as gastrointestinal intolerance&#44; dysgeusia&#44; hyporexia and vitamin B12 deficiency&#44;<a class="elsevierStyleCrossRef" href="#bib1195"><span class="elsevierStyleSup">54</span></a> the latter of which should be periodically monitored&#46;<a class="elsevierStyleCrossRef" href="#bib1200"><span class="elsevierStyleSup">55</span></a> Metformin is contraindicated for patients with glomerular filtration rates &#60;30<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#46;<a class="elsevierStyleCrossRefs" href="#bib1205"><span class="elsevierStyleSup">56&#44;57</span></a> Although lactic acidosis is uncommon&#44; half of patients older than 65 years present undiagnosed renal function&#46;<a class="elsevierStyleCrossRef" href="#bib1215"><span class="elsevierStyleSup">58</span></a> It is therefore important to periodically monitor the renal function and reduce the dosage if the glomerular filtration rate is &#60;45<span class="elsevierStyleHsp" style=""></span>mL&#47;min or discontinue it if &#60;30<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#46;<a class="elsevierStyleCrossRefs" href="#bib1220"><span class="elsevierStyleSup">59&#44;60</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">The use of metformin should be avoided in conditions of tissue hypoxia&#44; respiratory failure&#44; acute heart failure&#44; hepatic impairment and when there is acute intercurrent disease&#44; when iodinated contrast media is administered or when there is a risk of functional renal failure &#40;vomiting&#44; diarrhea&#41;&#46; The usefulness of metformin is highly limited in patients with anorexia and low weight&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Treatment should be started with a progressive titration from 425<span class="elsevierStyleHsp" style=""></span>mg&#47;day &#40;half of an 850-mg tablet&#41; to 1700<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#46; Higher dosages are not recommended because they increase the adverse effects without improving the efficacy&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Five percent of patients have to discontinue using the drug due to poor gastrointestinal tolerance&#44; a rate that can be higher in elderly patients&#46;<a class="elsevierStyleCrossRef" href="#bib1230"><span class="elsevierStyleSup">61</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Sulfonylureas</span><p id="par0165" class="elsevierStylePara elsevierViewall">These are low-cost and widely used drugs&#46; They reduce the microvascular complications of DM2<a class="elsevierStyleCrossRef" href="#bib1235"><span class="elsevierStyleSup">62</span></a> and increase the release of insulin by blocking the adenosine triphosphate-sensitive potassium channels in pancreatic beta cells&#46; Sulfonylureas should be used with caution given that the risk of severe hypoglycemia increases exponentially with age&#44; especially with glibenclamide&#44;<a class="elsevierStyleCrossRef" href="#bib1240"><span class="elsevierStyleSup">63</span></a> which is contraindicated for elderly patients&#44;<a class="elsevierStyleCrossRef" href="#bib1245"><span class="elsevierStyleSup">64</span></a> with glimepiride<a class="elsevierStyleCrossRef" href="#bib1250"><span class="elsevierStyleSup">65</span></a> or especially gliclazide being preferable&#44;<a class="elsevierStyleCrossRef" href="#bib1255"><span class="elsevierStyleSup">66</span></a> which produces the least hypoglycemia&#46;<a class="elsevierStyleCrossRefs" href="#bib1260"><span class="elsevierStyleSup">67&#44;68</span></a> Sulfonylureas also induce weight gain and are not recommended for patients with renal failure or high cardiovascular risk&#46; Hypoglycemia is boosted in the presence of renal or hepatic failure&#44; the concomitant administration of other oral diabetes drugs or insulin&#44; a recent hospital discharge&#44; advanced age&#44; reduced dietary intake and the use of 5 or more drugs&#46;<a class="elsevierStyleCrossRef" href="#bib1270"><span class="elsevierStyleSup">69</span></a> Sulfonylureas have multiple drug interactions &#40;salicylates&#44; dicoumarin agents&#44; sulfonamides&#44; &#64257;brates&#44; allopurinol&#44; methotrexate&#44; diuretics&#44; beta-blockers&#44; corticosteroids&#41;&#44; which complicate their use in polymedicated patients&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Meglitinides &#40;repaglinide&#44; nateglinide&#41;</span><p id="par0170" class="elsevierStylePara elsevierViewall">These are secretagogues&#44; as are sulfonylureas&#44; but with faster and shorter action and a higher cost&#46; They act preferentially on postprandial hyperglycemia&#46; Their more limited pharmacokinetic profile reduces the risk of hypoglycemia compared with sulfonylureas&#44;<a class="elsevierStyleCrossRef" href="#bib1275"><span class="elsevierStyleSup">70</span></a> especially in elderly patients with erratic eating patterns&#46;<a class="elsevierStyleCrossRef" href="#bib1280"><span class="elsevierStyleSup">71</span></a> Repaglinide&#44; due to its mainly biliary elimination&#44; can be used for patients with moderate to advanced renal failure&#46;<a class="elsevierStyleCrossRef" href="#bib1285"><span class="elsevierStyleSup">72</span></a> Combining the drug with gemfibrozil<a class="elsevierStyleCrossRef" href="#bib1290"><span class="elsevierStyleSup">73</span></a> or other drugs that activate or inhibit cytochrome P450 is contraindicated&#46; The drug should be administered approximately 15<span class="elsevierStyleHsp" style=""></span>min before meals&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Alpha-glucosidase inhibitors &#40;acarbose&#44; miglitol&#41;</span><p id="par0175" class="elsevierStylePara elsevierViewall">These drugs inhibit intestinal alpha-glucosidase&#44; slowing digestion and intestinal absorption of carbohydrates&#46; These inhibitors are especially aimed at controlling postprandial glycemia&#44; especially in patients who have carbohydrate-rich diets&#46; The drugs have systemic effects and can reduce the risk of cardiovascular events and arterial hypertension&#46;<a class="elsevierStyleCrossRef" href="#bib1295"><span class="elsevierStyleSup">74</span></a> Although the drugs do not induce hypoglycemia and can be potentially useful for some elderly patients with diabetes&#44;<a class="elsevierStyleCrossRefs" href="#bib1300"><span class="elsevierStyleSup">75&#44;76</span></a> their use can be limited by their low efficacy and high rate of adverse gastrointestinal effects &#40;flatulence&#44; diarrhea&#41;&#44; both in monotherapy and especially in combination with metformin&#46; These inhibitors can change digoxin and acenocoumarol levels&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Thiazolidinediones &#40;pioglitazone&#41;</span><p id="par0180" class="elsevierStylePara elsevierViewall">These agents act by increasing peripheral insulin sensitivity&#46; Thiazolidinediones provide longer-lasting glycemic control than metformin and sulfonylureas&#46;<a class="elsevierStyleCrossRef" href="#bib1310"><span class="elsevierStyleSup">77</span></a> Pioglitazone does not produce hypoglycemia and acts favorably on the lipid profile &#40;increased HDL-cholesterol and reduced triglyceride levels&#41;&#46; Pioglitazone can be beneficial in the secondary prevention of cardiovascular events &#40;proACTIVE study&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib1315"><span class="elsevierStyleSup">78</span></a> with reduced all-cause mortality&#46;<a class="elsevierStyleCrossRef" href="#bib1320"><span class="elsevierStyleSup">79</span></a> The drug has also been shown to histologically improve nonalcoholic steatohepatitis in patients with prediabetes or DM2&#46;<a class="elsevierStyleCrossRef" href="#bib1325"><span class="elsevierStyleSup">80</span></a> However&#44; pioglitazone has various adverse effects that limit its use in the elderly&#44;<a class="elsevierStyleCrossRefs" href="#bib1330"><span class="elsevierStyleSup">81&#44;82</span></a> such as weight gain&#44; salt and fluid retention&#44; dilutional anemia&#44; increased risk of heart failure&#44;<a class="elsevierStyleCrossRef" href="#bib1340"><span class="elsevierStyleSup">83</span></a> increased risk of fractures &#40;especially in postmenopausal women&#41;<a class="elsevierStyleCrossRef" href="#bib1345"><span class="elsevierStyleSup">84</span></a> and the possibility of accelerating cognitive impairment&#46;<a class="elsevierStyleCrossRef" href="#bib1350"><span class="elsevierStyleSup">85</span></a> The increased risk of bladder cancer with the long-term use of pioglitazone is a subject of debate&#46;<a class="elsevierStyleCrossRefs" href="#bib1355"><span class="elsevierStyleSup">86&#44;87</span></a></p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Dipeptidyl peptidase-4 inhibitors &#40;sitagliptin&#44; vildagliptin&#44; saxagliptin&#44; linagliptin&#44; alogliptin&#41;</span><p id="par0185" class="elsevierStylePara elsevierViewall">These drugs act by inhibiting the proteolytic dipeptidyl peptidase-4 &#40;DPP-4&#41; enzyme&#44; which degrades the incretin hormones&#44; increasing the availability and action of endogenous glucagon-like peptide-1 &#40;GLP-1&#41;&#46; DPP4i have been shown to be useful in monotherapy&#44; in combination with other hypoglycemic agents and in triple therapy&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">These oral drugs are well tolerated&#44; effective and safe in the short<a class="elsevierStyleCrossRefs" href="#bib1365"><span class="elsevierStyleSup">88&#44;89</span></a> and long term&#44;<a class="elsevierStyleCrossRefs" href="#bib1375"><span class="elsevierStyleSup">90&#44;91</span></a> in elderly and young patients with diabetes&#46;<a class="elsevierStyleCrossRef" href="#bib1385"><span class="elsevierStyleSup">92</span></a> The drugs have no effect on gastric emptying&#44; do not induce reduced central intake and do not cause gastrointestinal intolerance or weight loss&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">DPP4i do not induce hypoglycemia &#40;glucose-dependent mechanism&#41;&#44; do not change body weight and have no significant drug interactions&#44; which makes them an attractive therapeutic option for treating DM2 in the elderly&#46; These inhibitors do not require dose adjustments in elderly patients&#46; Several studies have shown the safety and efficacy of vildagliptin&#44;<a class="elsevierStyleCrossRefs" href="#bib1390"><span class="elsevierStyleSup">93&#8211;95</span></a> sitagliptin&#44;<a class="elsevierStyleCrossRefs" href="#bib1405"><span class="elsevierStyleSup">96&#44;97</span></a> saxagliptin&#44;<a class="elsevierStyleCrossRefs" href="#bib1405"><span class="elsevierStyleSup">96&#8211;101</span></a> linagliptin<a class="elsevierStyleCrossRefs" href="#bib1435"><span class="elsevierStyleSup">102&#8211;104</span></a> and alogliptin<a class="elsevierStyleCrossRef" href="#bib1450"><span class="elsevierStyleSup">105</span></a> in elderly patients&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">DPP4i have shown their cardiovascular safety in clinical trials performed on patients with high cardiovascular risk&#44;<a class="elsevierStyleCrossRefs" href="#bib1455"><span class="elsevierStyleSup">106&#8211;108</span></a> including patients older than 75 years&#46;<a class="elsevierStyleCrossRef" href="#bib1470"><span class="elsevierStyleSup">109</span></a> In the SAVOR-TIMI 53 study&#44;<a class="elsevierStyleCrossRef" href="#bib1455"><span class="elsevierStyleSup">106</span></a> the use of saxagliptin was associated with a significant increase in hospitalizations for heart failure&#44; especially among patients with high baseline levels of B-type natriuretic peptide &#40;BNP&#41; or with a prior history of heart failure or chronic renal failure&#46;<a class="elsevierStyleCrossRefs" href="#bib1475"><span class="elsevierStyleSup">110&#44;111</span></a> The EXAMINE study<a class="elsevierStyleCrossRef" href="#bib1460"><span class="elsevierStyleSup">107</span></a> also observed a greater tendency &#40;although not significant&#41; to develop heart failure among patients treated with alogliptin&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">However&#44; extensive observational studies in standard clinical practice<a class="elsevierStyleCrossRef" href="#bib1485"><span class="elsevierStyleSup">112</span></a> and the TECOS study with sitagliptin<a class="elsevierStyleCrossRef" href="#bib1490"><span class="elsevierStyleSup">113</span></a> could not confirm an association between these drugs and an increased rate of heart failure&#46; Furthermore&#44; separate meta-analyses of patients with DM2 treated with vildagliptin<a class="elsevierStyleCrossRef" href="#bib1495"><span class="elsevierStyleSup">114</span></a> or linagliptin<a class="elsevierStyleCrossRef" href="#bib1500"><span class="elsevierStyleSup">115</span></a> support its cardiovascular safety and the absence of heart failure risk&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">Vildagliptin is the only DPP4i that has had a clinical trial with patients with DM2 and chronic heart failure &#40;NYHA functional class <span class="elsevierStyleSmallCaps">I&#8211;III</span>&#41; with a left ventricular ejection fraction &#60;40&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib1505"><span class="elsevierStyleSup">116</span></a> Treatment with vildagliptin&#44; compared with placebo&#44; was not associated with significant changes in the latter&#44; thereby meeting the objective of noninferiority&#46;<a class="elsevierStyleCrossRef" href="#bib1505"><span class="elsevierStyleSup">116</span></a></p><p id="par0215" class="elsevierStylePara elsevierViewall">DPP4i can be used safely&#44; without the risk of hypoglycemia&#44; at any stage of chronic renal failure&#46; All of these inhibitors require dose adjustments in cases of moderate to severe renal failure&#44; except for linagliptin&#44; which is eliminated by the bile duct&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">DPP4i have few drug interactions&#44; an important advantage for elderly patients&#44; for whom polypharmacy is common&#46;<a class="elsevierStyleCrossRef" href="#bib1510"><span class="elsevierStyleSup">117</span></a> Vildagliptin is not metabolized by cytochrome P450 and therefore has a lower risk of interactions&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Glucagon-like peptide-1 receptor agonists &#40;exenatide&#44; liraglutide&#44; lixisenatide&#44; exenatide-LAR&#44; dulaglutide&#41;</span><p id="par0225" class="elsevierStylePara elsevierViewall">GLP-1 receptor agonists &#40;GLP-1 RA&#41; act by activating GLP-1 receptors&#44; which results in increased insulin secretion and reduced glucagon secretion&#44; depending on the blood glucose level&#46; The agonists also slow gastric emptying and increase the feeling of central satiety&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">These drugs induce significant weight loss and are therefore an option when weight loss is a priority &#40;e&#46;g&#46;&#44; elderly with advanced gonarthrosis&#44; sleep apnea syndrome&#44; hypoventilation&#44; steatohepatitis and metabolic syndrome&#41;&#46; However&#44; weight loss and reduced appetite can have undesirable effects in frail elderly patients&#44; for whom hyporexia and malnutrition are common&#46; The presence of sarcopenic obesity is common among elderly patients &#40;excess adiposity with little lean mass due to loss of muscle mass&#41;&#46; Sarcopenia is a marker of a poor functional and vital prognosis&#46; Weight loss &#40;a desirable objective in most patients with DM2&#41; at the cost of lean mass can therefore be counterproductive&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">GLP-1 RAs do not induce hypoglycemia but are associated with frequent gastrointestinal discomfort &#40;nausea&#44; vomiting and diarrhea&#41;&#46; In addition to their high cost&#44; the agonists require subcutaneous administration &#40;daily in 2 doses in the case of exenatide&#59; daily in 1 dose for liraglutide and lixisenatide&#59; and weekly with exenatide-LAR and dulaglutide&#41;&#46; We should therefore ensure that the patient or caregiver have an appropriate level of dexterity before prescribing these drugs&#46; Although there is controversy on the possible onset of pancreatitis with the use of GLP-1 RAs&#44; various studies have not confirmed this association&#44; considering that the higher incidence of pancreatitis is the result of having diabetes&#46;<a class="elsevierStyleCrossRef" href="#bib1515"><span class="elsevierStyleSup">118</span></a></p><p id="par0240" class="elsevierStylePara elsevierViewall">GLP-1 RAs have shown a good cardiovascular safety profile in patients with DM2 of high vascular risk&#46; Compared with placebo&#44; lixisenatide<a class="elsevierStyleCrossRef" href="#bib1520"><span class="elsevierStyleSup">119</span></a> and exenatide LAR<a class="elsevierStyleCrossRef" href="#bib1525"><span class="elsevierStyleSup">120</span></a> have shown noninferiority&#44; while liraglutide<a class="elsevierStyleCrossRef" href="#bib1530"><span class="elsevierStyleSup">121</span></a> and semaglutide &#40;an unmarketed GLP-1 RA that is administered weekly&#41;<a class="elsevierStyleCrossRef" href="#bib1535"><span class="elsevierStyleSup">122</span></a> showed a reduction in cardiovascular events&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">There have been no specific studies with GLP-1 RA in elderly individuals&#46; All analyses by subgroups in patients 65 years of age or older achieved a greater reduction in HbA1c&#44; fewer hypoglycemic events and greater weight loss&#44; although with more gastrointestinal effects than the comparator &#40;glimepiride&#44;<a class="elsevierStyleCrossRef" href="#bib1540"><span class="elsevierStyleSup">123</span></a> sitagliptin&#44;<a class="elsevierStyleCrossRefs" href="#bib1545"><span class="elsevierStyleSup">124&#44;125</span></a> insulin glargine<a class="elsevierStyleCrossRefs" href="#bib1555"><span class="elsevierStyleSup">126&#8211;128</span></a> or placebo&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1570"><span class="elsevierStyleSup">129</span></a> Significant differences have not been observed in terms of safety and efficacy compared with younger patients&#46;<a class="elsevierStyleCrossRef" href="#bib1575"><span class="elsevierStyleSup">130</span></a> In a meta-analysis with lixisenatide<a class="elsevierStyleCrossRef" href="#bib1570"><span class="elsevierStyleSup">129</span></a> and in a grouped analysis with liraglutide&#44;<a class="elsevierStyleCrossRef" href="#bib1575"><span class="elsevierStyleSup">130</span></a> the results for patients older than 65 years were similar to those observed in other age groups&#46; Nevertheless&#44; none of these studies included vulnerable or frail elderly individuals&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall">In conclusion&#44; GLP-1 RAs can be used with caution in elderly patients&#44; customizing their indication &#40;e&#46;g&#46;&#44; elderly patients with obesity and good functional status&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1580"><span class="elsevierStyleSup">131</span></a> These drugs should not be administered to frail elderly patients<a class="elsevierStyleCrossRef" href="#bib1075"><span class="elsevierStyleSup">30</span></a> or those with a history of pancreatitis and&#47;or glomerular filtration rates &#60;30<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#46;<a class="elsevierStyleCrossRef" href="#bib1585"><span class="elsevierStyleSup">132</span></a></p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Sodium-glucose cotransporter 2 inhibitors &#40;dapagliflozin&#44; canagliflozin&#44; empagliflozin&#41;</span><p id="par0255" class="elsevierStylePara elsevierViewall">These drugs inhibit the sodium-glucose cotransporter 2 &#40;SGLT2&#41; in the renal tubule&#44; preventing the reabsorption of glucose and inducing glycosuria&#46; Given that their mechanism of action is independent of insulin&#44;<a class="elsevierStyleCrossRef" href="#bib1590"><span class="elsevierStyleSup">133</span></a> SGLT2 inhibitors are effective in all stages of DM2 and do not produce hypoglycemia&#46; Due to their glycosuric effect&#44; SGLT2 inhibitors induce a mean weight loss of 1&#46;8&#8211;2<span class="elsevierStyleHsp" style=""></span>kg&#44; at the expense especially of fat mass&#44; and have a hypotensive effect that causes a mean reduction in systolic blood pressure of &#8722;4&#46;45<span class="elsevierStyleHsp" style=""></span>mmHg&#46;<a class="elsevierStyleCrossRefs" href="#bib1595"><span class="elsevierStyleSup">134&#44;135</span></a> Glycosuria causes osmotic diuresis and polyuria&#46;</p><p id="par0260" class="elsevierStylePara elsevierViewall">These are effective drugs that have shown superiority in glycemic control against sulfonylureas<a class="elsevierStyleCrossRefs" href="#bib1605"><span class="elsevierStyleSup">136&#44;137</span></a> and sitagliptin&#46;<a class="elsevierStyleCrossRef" href="#bib1615"><span class="elsevierStyleSup">138</span></a> The expected reduction in HbA1c levels varies between 0&#46;7&#37; and 1&#37;&#44; sustained up to 3 years of follow-up&#46;</p><p id="par0265" class="elsevierStylePara elsevierViewall">SGLT2 inhibitors are administered in a single daily dose orally&#44; are effective in monotherapy<a class="elsevierStyleCrossRef" href="#bib1620"><span class="elsevierStyleSup">139</span></a> &#40;if there is a contraindication or intolerance to metformin&#41;&#44; as a second hypoglycemic agent and in triple therapy&#46; Hypoglycemia can occur when combining these inhibitors with sulfonylureas or insulin&#46; Therefore&#44; the dosage needs to be reduced or the discontinuation of the sulfonylureas needs to be assessed&#46;<a class="elsevierStyleCrossRef" href="#bib1625"><span class="elsevierStyleSup">140</span></a></p><p id="par0270" class="elsevierStylePara elsevierViewall">In the EMPA-REG study&#44; performed on patients with DM2&#44; cardiovascular disease and a glomerular filtration rate &#62;30<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#46;72<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#44; empagliflozin decreased overall mortality by 32&#37;&#44; hospitalizations for heart failure by 35&#37; and mortality due to cardiovascular causes by 38&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib1630"><span class="elsevierStyleSup">141</span></a> In this study&#44; empagliflozin showed a nephroprotective effect&#44; delaying the progression of renal failure and the need for dialysis&#46;<a class="elsevierStyleCrossRef" href="#bib1635"><span class="elsevierStyleSup">142</span></a> Based on these results&#44; the latest guidelines from the European Society of Cardiology recommend considering the use of the SGLT2 inhibitor empagliflozin in patients with heart failure and DM2&#46;<a class="elsevierStyleCrossRef" href="#bib1640"><span class="elsevierStyleSup">143</span></a></p><p id="par0275" class="elsevierStylePara elsevierViewall">More recently&#44; the results of the study on equivalent cardiovascular safety with canagliflozin have been published&#46;<a class="elsevierStyleCrossRef" href="#bib1645"><span class="elsevierStyleSup">144</span></a> This study involved a grouped analysis of the CANVAS and CANVAS-R studies&#44; which included 10&#44;142 patients with DM2 and high cardiovascular risk&#46; The patients treated with canagliflozin had a 14&#37; reduction &#40;hazard ratio &#91;HR&#93;&#44; 0&#46;8&#59; 95&#37; confidence interval &#91;95&#37; CI&#93; 0&#46;75&#8211;0&#46;97&#41; in the risk of events included globally in the primary endpoint &#40;a composite of death by cardiovascular cause&#44; nonfatal myocardial infarction and nonfatal stroke&#41;&#46; Statistical significance was not reached&#44; however&#44; in reducing each of these events separately&#46; Hospitalization for heart failure was reduced by 33&#37; &#40;HR&#44; 0&#46;67&#59; 95&#37; CI 0&#46;52&#8211;0&#46;87&#41;&#46; The results showed renal benefits with canagliflozin&#44; reducing both the progression of albuminuria &#40;HR&#44; 0&#46;73&#59; 95&#37; CI 0&#46;67&#8211;0&#46;79&#41; and the composite result of a sustained reduction of 40&#37; in the estimated glomerular filtration rate and death by renal causes &#40;HR&#44; 0&#46;60&#59; 95&#37; CI 0&#46;47&#8211;0&#46;77&#41;&#46; A more detailed analysis of these results is being performed&#44; which has still not been incorporated in the international recommendations&#46;</p><p id="par0280" class="elsevierStylePara elsevierViewall">The most common adverse effect of these drugs is genital mycoses&#44; especially in women&#46; A slight increase has also been reported in urinary tract infections&#46;<a class="elsevierStyleCrossRef" href="#bib1645"><span class="elsevierStyleSup">144</span></a> In elderly individuals&#44; we should consider the potential adverse effects related to volume depletion secondary to osmotic diuresis &#40;dehydration&#44; electrolyte disorders&#44; hypotension and renal failure&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1650"><span class="elsevierStyleSup">145</span></a> Given the drugs&#8217; hypotensive effect&#44; it is important to rule out the presence of orthostatic hypotension&#44; which is common in elderly patients with diabetes&#46;<a class="elsevierStyleCrossRef" href="#bib1655"><span class="elsevierStyleSup">146</span></a> Although a study with canagliflozin observed an increased number of fractures &#40;extremities but not hip&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib1660"><span class="elsevierStyleSup">147</span></a> possibly related to an increased risk of falls&#44; this association was not confirmed in a subsequent study&#46;<a class="elsevierStyleCrossRef" href="#bib1665"><span class="elsevierStyleSup">148</span></a> The CANVAS study confirmed a greater tendency for fractures in patients treated with canagliflozin versus placebo &#40;HR&#44; 1&#46;23&#59; 95&#37; CI 0&#46;99&#8211;1&#46;52&#41;&#46; In this study&#44; treatment with canagliflozin was associated with a higher risk of amputation&#44; mainly of toes and the metatarsal &#40;6&#46;3 vs&#46; 3&#46;4 participants with amputation per 1000 patient-years&#44; which corresponds to a risk ratio of 1&#46;97&#59; 95&#37; CI 1&#46;41&#8211;2&#46;75&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1645"><span class="elsevierStyleSup">144</span></a> Finally&#44; rare cases of normoglycemic ketoacidosis have been reported &#40;with only slightly elevated blood glucose readings&#41;&#44; especially in long-standing DM2 in conditions of insulinopenia or latent autoimmune diabetes in adults in which an insulin dose reduction was performed&#46; Normoglycemic ketoacidosis has also been reported in fasting conditions&#44; with excessive alcohol consumption&#44; extreme physical exercise and intercurrent acute processes&#46;<a class="elsevierStyleCrossRef" href="#bib1670"><span class="elsevierStyleSup">149</span></a></p><p id="par0285" class="elsevierStylePara elsevierViewall">The action of these drugs depends on the renal function&#44; such that their efficacy decreases when the glomerular filtration rate is &#60;60<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#46;72<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#46; Dapagliflozin should not be administered below this filtration rate&#59; however&#44; empagliflozin and canagliflozin may be used&#44; with reduced dosages&#44;<a class="elsevierStyleCrossRefs" href="#bib1675"><span class="elsevierStyleSup">150&#44;151</span></a> for GFRs between 45 and 60<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#46;72<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> and discontinued for GFRs &#60;30<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#46;72<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#46;</p><p id="par0290" class="elsevierStylePara elsevierViewall">There is little experience on the use of SGLT2 inhibitors in the elderly population and should therefore be indicated with caution and individually in selected patients&#46;<a class="elsevierStyleCrossRef" href="#bib1685"><span class="elsevierStyleSup">152</span></a> Canagliflozin has had a number of studies with elderly patients of up to 80 years of age&#44; which has shown a safety and efficacy comparable to that with younger patients&#46;<a class="elsevierStyleCrossRefs" href="#bib1650"><span class="elsevierStyleSup">145&#44;147&#44;148&#44;153&#8211;155</span></a> Furthermore&#44; the analysis by age subgroup with empagliflozin<a class="elsevierStyleCrossRef" href="#bib1620"><span class="elsevierStyleSup">139</span></a> and dapagliflozin<a class="elsevierStyleCrossRefs" href="#bib1705"><span class="elsevierStyleSup">156&#8211;158</span></a> has shown similar results to those obtained in younger patients&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Insulin</span><p id="par0295" class="elsevierStylePara elsevierViewall">Insulin is the most potent hypoglycemic agent and acts by activating the insulin receptors&#44; decreasing glucose production by the liver and promoting the peripheral use of glucose&#46; In Spain&#44; 20&#37; of patients with diabetes older than 75 years were treated with insulin in monotherapy or combined with other antidiabetic agents&#46;<a class="elsevierStyleCrossRef" href="#bib1720"><span class="elsevierStyleSup">159</span></a></p><p id="par0300" class="elsevierStylePara elsevierViewall">Patients older than 80 years treated with insulin have a greater risk of severe hypoglycemia&#44;<a class="elsevierStyleCrossRef" href="#bib1060"><span class="elsevierStyleSup">27</span></a> falls and fractures&#46;<a class="elsevierStyleCrossRef" href="#bib1725"><span class="elsevierStyleSup">160</span></a> To minimize these risks&#44; insulin therapy for the elderly should be individualized&#44; emphasizing patient safety&#46; It is worth remembering that HbA1c levels are not a reliable predictor of the risk of hypoglycemia&#46;<a class="elsevierStyleCrossRef" href="#bib1730"><span class="elsevierStyleSup">161</span></a></p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Basal insulinization</span><p id="par0305" class="elsevierStylePara elsevierViewall">The starting daily dose should be lower &#40;0&#46;1&#8211;0&#46;2<span class="elsevierStyleHsp" style=""></span>IU&#47;kg&#41; than for younger patients with DM2&#44; especially for frail elderly patients&#44; those with low weight and those with renal failure&#46; Dose adjustments should be performed gradually and progressively&#46;</p><p id="par0310" class="elsevierStylePara elsevierViewall">When treatment is started with a basal insulin&#44; it is recommended that the treatment with metformin be maintained to reduce the insulin requirements&#46;<a class="elsevierStyleCrossRef" href="#bib1735"><span class="elsevierStyleSup">162</span></a> The combination of basal insulin and oral secretagogues &#40;sulfonylureas&#44; glinides&#41; is not safe for elderly patients due to the high risk of hypoglycemia&#46; The maintenance or discontinuation of other noninsulin antidiabetic drugs should be individually assessed&#44; considering the complexity of the treatment and its costs&#46;<a class="elsevierStyleCrossRef" href="#bib1735"><span class="elsevierStyleSup">162</span></a></p><p id="par0315" class="elsevierStylePara elsevierViewall">Although they have not demonstrated superiority in glycemic control&#44; basal insulin analogs &#40;glargine 100<span class="elsevierStyleHsp" style=""></span>U and 300<span class="elsevierStyleHsp" style=""></span>U&#44; detemir&#44; degludec&#41; have a lower risk of hypoglycemia &#40;especially nocturnal&#41; than human neutral protamine Hagedorn insulin&#44;<a class="elsevierStyleCrossRefs" href="#bib1740"><span class="elsevierStyleSup">163&#8211;165</span></a> and can therefore be preferable for elderly patients despite the drugs&#8217; higher cost&#46; Compared with insulin glargine 100<span class="elsevierStyleHsp" style=""></span>U&#44; both insulin glargine 300U<a class="elsevierStyleCrossRef" href="#bib1755"><span class="elsevierStyleSup">166</span></a> and insulin degludec<a class="elsevierStyleCrossRefs" href="#bib1760"><span class="elsevierStyleSup">167&#44;168</span></a> have shown a lower rate of hypoglycemia &#40;especially nocturnal&#41; and greater flexibility in the administration schedule&#44; due to their lower variability and longer drug action&#46; These characteristics favorably place these new insulins for the management of elderly institutionalized patients&#44; although studies are needed on this population&#46;<a class="elsevierStyleCrossRef" href="#bib1770"><span class="elsevierStyleSup">169</span></a></p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Basal insulin intensification</span><p id="par0320" class="elsevierStylePara elsevierViewall">When the glycemic control objectives are not met with a basal insulin regimen&#44; the insulin therapy needs to be intensified&#44; either by adding a dose of prandial insulin in the main meal &#40;basal-plus&#41;&#44; in the 3 main meals &#40;basal-bolus&#41; or transitioning to a regimen of 2 or 3 daily doses of premixed insulin&#46; These complex insulin therapy regimens are associated with a significant risk of hypoglycemia<a class="elsevierStyleCrossRefs" href="#bib1740"><span class="elsevierStyleSup">163&#44;170&#44;171</span></a> and represent a significant burden of care&#44; including the need for repeated capillary blood glucose checks&#46;</p><p id="par0325" class="elsevierStylePara elsevierViewall">If prandial insulin is required&#44; rapid-acting insulin analogs are preferable to regular insulin due the former&#39;s lower rate of hypoglycemia&#46;<a class="elsevierStyleCrossRef" href="#bib1785"><span class="elsevierStyleSup">172</span></a> Biphasic or premixed insulins&#44; such as insulin aspart and insulin glulisine&#44; can be administered after meals<a class="elsevierStyleCrossRefs" href="#bib1775"><span class="elsevierStyleSup">170&#44;173&#44;174</span></a> and improve glycemic control in patients poorly controlled with basal insulin but are associated with a higher risk of hypoglycemia and weight gain&#46;<a class="elsevierStyleCrossRefs" href="#bib1780"><span class="elsevierStyleSup">171&#44;175</span></a> Premixed insulins have an inflexible pharmacokinetic profile and are therefore only indicated for elderly patients with regular schedules and patterns of dietary intake and physical activity&#46; In these cases&#44; premixed insulins can provide glycemic control similar to that of the more complex basal-bolus regimen&#46;<a class="elsevierStyleCrossRef" href="#bib1805"><span class="elsevierStyleSup">176</span></a></p><p id="par0330" class="elsevierStylePara elsevierViewall">In elderly patients with difficult-to-control or highly progressed DM2 with insulinopenia and a good capacity for self-care&#44; the basal-bolus regimen can provide appropriate glycemic control with a good safety profile and patient satisfaction&#46;<a class="elsevierStyleCrossRef" href="#bib1810"><span class="elsevierStyleSup">177</span></a></p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Insulin devices</span><p id="par0335" class="elsevierStylePara elsevierViewall">Another issue to consider is the various devices for administering insulin and choosing that which best fits the patient&#39;s abilities and capabilities&#46; By far&#44; the most widely used is the pen type&#46; To detect elderly patients with problems in self-administering insulin&#44; a test known as the &#8220;clock-drawing test&#8221; is employed to assess cognitive impairment and the presence of constructional apraxia&#46;<a class="elsevierStyleCrossRef" href="#bib1815"><span class="elsevierStyleSup">178</span></a> The test consists of having the patient draw &#40;on a blank sheet of paper&#41; a clock indicating ten past eleven&#46;</p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Combined therapies</span><p id="par0340" class="elsevierStylePara elsevierViewall">In the elderly&#44; it is essential to simplify insulin therapy as much as possible to reduce the risk of hypoglycemia and minimize the burden of care associated with the complex insulin regimens&#46;<a class="elsevierStyleCrossRef" href="#bib1730"><span class="elsevierStyleSup">161</span></a> As has been mentioned&#44; oral diabetes drugs should be maintained &#40;except for sulfonylureas&#47;glinides&#41; with the basal insulin to reduce the insulin requirements and risks of hypoglycemia&#46;<a class="elsevierStyleCrossRefs" href="#bib1735"><span class="elsevierStyleSup">162&#44;179</span></a> DPP4i have an especially appropriate profile in this population due to their low risk of hypoglycemia and broad experience with their use in elderly patients with frailty and renal failure&#46; Their combination with basal insulin allows for the insulin dosage to be reduced and minimizes the adverse effects of the insulin &#40;hypoglycemia&#44; weight gain&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1825"><span class="elsevierStyleSup">180</span></a></p><p id="par0345" class="elsevierStylePara elsevierViewall">The combined therapy of basal insulin and GLP-1 RA provides excellent glycemic control and a lower risk of hypoglycemia than the complex insulin regimens&#46;<a class="elsevierStyleCrossRef" href="#bib1830"><span class="elsevierStyleSup">181</span></a> There have been studies with fixed-dose combinations of basal insulin and GLP-1 RA &#40;degludec and liraglutide&#59; glargine and lixisenatide&#41; that facilitate the posology and improve the gastrointestinal tolerance to GLP-1 RA&#46; These combinations can therefore play a role in treating DM2 in the elderly&#46; Nevertheless&#44; the lesser experience with using these combinations in the elderly&#44; a lack of specific studies and the combinations&#8217; higher cost make careful patient selection a necessity&#46;</p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Therapy deintensification</span><p id="par0350" class="elsevierStylePara elsevierViewall">Elderly patients with diabetes are frequently overtreated&#46;<a class="elsevierStyleCrossRefs" href="#bib1030"><span class="elsevierStyleSup">21&#44;22</span></a> Antidiabetic therapy deintensification is therefore appropriate after a comprehensive geriatric assessment has been conducted&#44; indicating less complex and safer regimens &#40;with a lower risk of hypoglycemia&#44; lower burden of care&#44; better tolerance and no drug interactions&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1835"><span class="elsevierStyleSup">182</span></a> The simplification of complex insulin regimens in elderly patients reduces the risk of hypoglycemia and the burden of care&#44; without compromising glycemic control&#46;<a class="elsevierStyleCrossRef" href="#bib1730"><span class="elsevierStyleSup">161</span></a> In this respect&#44; it is worth remembering that a high HbA1c level does not rule out the risk of hypoglycemia in the elderly&#46;<a class="elsevierStyleCrossRefs" href="#bib1050"><span class="elsevierStyleSup">25&#44;161</span></a></p></span></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Therapeutic algorithm for type 2 diabetes in elderly patients &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;</span><p id="par0355" class="elsevierStylePara elsevierViewall"> The planning of DM2 therapy for elderly patients should be based on a comprehensive geriatric assessment&#46; If the elderly patient is frail&#44; dependent or has moderate to severe dementia&#44; the priority objective is to prevent symptomatic hypoglycemia and hyperglycemia&#46; The antidiabetic agents recommended in these cases would be metformin and DPP4i&#46; Other antidiabetic drugs not associated with a significant risk of hypoglycemia have adverse effects that limit their use in this population&#44; effects such as hypotension&#44; dehydration and renal failure &#40;with SGLT2i&#41; and nausea&#44; vomiting&#44; diarrhea and weight loss &#40;with GLP-1 RA&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0360" class="elsevierStylePara elsevierViewall">Renal failure is a prevalent comorbidity in elderly patients with diabetes and affects the treatment options&#46;<a class="elsevierStyleCrossRef" href="#bib1840"><span class="elsevierStyleSup">183</span></a> In Spain&#44; the prevalence of stage 4 and 5 chronic kidney disease &#40;glomerular filtration rate &#60;30<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#41; in patients with DM2 aged 70&#8211;79 years and &#8805;80 years is approximately 30&#37; and 50&#37;&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib1845"><span class="elsevierStyleSup">184</span></a> In these circumstances&#44; the preferred therapeutic options are DPP4i and insulin&#46; Although repaglinide and pioglitazone may be used from a pharmacokinetic standpoint&#44; their adverse effects profile &#40;hypoglycemia with repaglinide&#59; heart failure and fractures with pioglitazone&#41; make them an inadvisable option&#46;<a class="elsevierStyleCrossRef" href="#bib1850"><span class="elsevierStyleSup">185</span></a></p><p id="par0365" class="elsevierStylePara elsevierViewall">Finally&#44; for elderly patients with a high cardiovascular risk and none of the previously mentioned clinical limitations &#40;moderate&#8211;severe renal failure&#44; frailty&#44; dementia&#41;&#44; the priority should be to select antidiabetic drugs that have shown cardiovascular benefits&#44; such as empagliflozin and liraglutide&#46; Other drugs that have shown cardiovascular safety include metformin&#44; pioglitazone and DPP4i&#46;</p></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Conflict of interest</span><p id="par0370" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:14 [
        0 => array:3 [
          "identificador" => "xres991073"
          "titulo" => "Abstract"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abst0005"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec954991"
          "titulo" => "Keywords"
        ]
        2 => array:3 [
          "identificador" => "xres991072"
          "titulo" => "Resumen"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abst0010"
            ]
          ]
        ]
        3 => array:2 [
          "identificador" => "xpalclavsec954992"
          "titulo" => "Palabras clave"
        ]
        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Background"
        ]
        5 => array:2 [
          "identificador" => "sec0010"
          "titulo" => "Functional capacity&#44; frailty and diabetes"
        ]
        6 => array:2 [
          "identificador" => "sec0015"
          "titulo" => "Hypoglycemia in elderly patients"
        ]
        7 => array:2 [
          "identificador" => "sec0020"
          "titulo" => "General principles in the treatment of elderly patients with type 2 diabetes"
        ]
        8 => array:2 [
          "identificador" => "sec0025"
          "titulo" => "Glycemic control objectives for elderly patients"
        ]
        9 => array:2 [
          "identificador" => "sec0030"
          "titulo" => "Nonpharmacological treatment&#58; nutrition and physical activity"
        ]
        10 => array:3 [
          "identificador" => "sec0035"
          "titulo" => "Pharmacotherapy"
          "secciones" => array:14 [
            0 => array:2 [
              "identificador" => "sec0040"
              "titulo" => "Metformin"
            ]
            1 => array:2 [
              "identificador" => "sec0045"
              "titulo" => "Sulfonylureas"
            ]
            2 => array:2 [
              "identificador" => "sec0050"
              "titulo" => "Meglitinides &#40;repaglinide&#44; nateglinide&#41;"
            ]
            3 => array:2 [
              "identificador" => "sec0055"
              "titulo" => "Alpha-glucosidase inhibitors &#40;acarbose&#44; miglitol&#41;"
            ]
            4 => array:2 [
              "identificador" => "sec0060"
              "titulo" => "Thiazolidinediones &#40;pioglitazone&#41;"
            ]
            5 => array:2 [
              "identificador" => "sec0065"
              "titulo" => "Dipeptidyl peptidase-4 inhibitors &#40;sitagliptin&#44; vildagliptin&#44; saxagliptin&#44; linagliptin&#44; alogliptin&#41;"
            ]
            6 => array:2 [
              "identificador" => "sec0070"
              "titulo" => "Glucagon-like peptide-1 receptor agonists &#40;exenatide&#44; liraglutide&#44; lixisenatide&#44; exenatide-LAR&#44; dulaglutide&#41;"
            ]
            7 => array:2 [
              "identificador" => "sec0075"
              "titulo" => "Sodium-glucose cotransporter 2 inhibitors &#40;dapagliflozin&#44; canagliflozin&#44; empagliflozin&#41;"
            ]
            8 => array:2 [
              "identificador" => "sec0080"
              "titulo" => "Insulin"
            ]
            9 => array:2 [
              "identificador" => "sec0085"
              "titulo" => "Basal insulinization"
            ]
            10 => array:2 [
              "identificador" => "sec0090"
              "titulo" => "Basal insulin intensification"
            ]
            11 => array:2 [
              "identificador" => "sec0095"
              "titulo" => "Insulin devices"
            ]
            12 => array:2 [
              "identificador" => "sec0100"
              "titulo" => "Combined therapies"
            ]
            13 => array:2 [
              "identificador" => "sec0105"
              "titulo" => "Therapy deintensification"
            ]
          ]
        ]
        11 => array:2 [
          "identificador" => "sec0110"
          "titulo" => "Therapeutic algorithm for type 2 diabetes in elderly patients &#40;Fig&#46; 1&#41;"
        ]
        12 => array:2 [
          "identificador" => "sec0115"
          "titulo" => "Conflict of interest"
        ]
        13 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2017-10-11"
    "fechaAceptado" => "2017-12-03"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec954991"
          "palabras" => array:3 [
            0 => "Type 2 diabetes mellitus"
            1 => "Elderly"
            2 => "Antidiabetic treatment"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec954992"
          "palabras" => array:3 [
            0 => "Diabetes mellitus tipo 2"
            1 => "Anciano"
            2 => "Tratamiento antidiab&#233;tico"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The prevalence of type 2 diabetes mellitus &#40;DM2&#41; increases markedly with age&#46; Antidiabetic treatment and the objectives of glycaemic control in elderly patients with DM2 should be individualized according to their biopsychosocial characteristics&#46; In elderly patients for whom the benefits of intensive antidiabetic treatment are limited&#44; the basic objectives should be to improve the quality of life&#44; preserve functionality and avoid adverse effects&#44; especially hypoglycaemia&#46; Treatment of DM2 in the elderly was the subject of a consensus document published in 2012 and endorsed by several Spanish scientific societies&#46; Since then&#44; new therapeutic groups and evidence have emerged that warrant an update to this consensus document&#46; The present document focuses on the therapeutic aspects of DM2 in elderly patients&#44; understood as being older than 75 years or frail&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La prevalencia de la diabetes mellitus tipo 2 &#40;DM2&#41; se incrementa marcadamente con la edad&#46; El tratamiento antidiab&#233;tico y los objetivos de control gluc&#233;mico en el anciano con DM2 deben individualizarse en funci&#243;n de sus caracter&#237;sticas biopsicosociales&#46; En los pacientes de edad avanzada&#44; en los que los beneficios de un tratamiento antidiab&#233;tico intensivo son limitados&#44; los objetivos b&#225;sicos deben ser mejorar la calidad de vida&#44; preservar la funcionalidad y evitar los efectos adversos&#44; muy especialmente las hipoglucemias&#46; El tratamiento de la DM2 en el anciano fue objeto de un consenso&#44; publicado en 2012 y avalado por varias sociedades cient&#237;ficas espa&#241;olas&#46; Desde entonces&#44; han aparecido nuevos grupos terap&#233;uticos y evidencias que hacen recomendable su actualizaci&#243;n&#46; El presente documento se centrar&#225; en los aspectos terap&#233;uticos de la DM2 en el paciente anciano&#44; entendiendo como tal el tener una edad mayor de 75 a&#241;os o presentar fragilidad&#46;</p></span>"
      ]
    ]
    "NotaPie" => array:2 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; G&#243;mez-Huelgas R&#44; G&#243;mez Peralta F&#44; Rodr&#237;guez Ma&#241;as L&#44; Formiga F&#44; Puig Domingo M&#44; Mediavilla Bravo JJ&#44; et al&#46; Tratamiento de la diabetes mellitus tipo 2 en el paciente anciano&#46; Rev Clin Esp&#46; 2018&#59;218&#58;74&#8211;88&#46;</p>"
      ]
      1 => array:2 [
        "etiqueta" => "&#9734;&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">This article is published simultaneously in <span class="elsevierStyleInterRef" id="intr0010" href="https://doi.org/10.1016/j.regg.2017.12.003">https&#58;&#47;&#47;doi&#46;org&#47;10&#46;1016&#47;j&#46;regg&#46;2017&#46;12&#46;003</span>&#44; with the consent of the authors and editors&#46;</p>"
      ]
    ]
    "multimedia" => array:2 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1519
            "Ancho" => 2506
            "Tamanyo" => 258442
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Treatment algorithm for type 2 diabetes mellitus in elderly patients&#46;</p> <p id="spar0020" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; DPP4i&#58; dipeptidyl peptidase-4 inhibitors&#59; GLP-1RA&#58; glucagon-like peptide-1 receptor agonists&#59; SGLT2i&#58; sodium-glucose cotransporter 2 inhibitors&#46;</p> <p id="spar0025" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">a</span> Repaglinide and pioglitazone can be used in patients with GFR &#60;30<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#44; but their use is not recommended due to the risk of adverse effects&#58; hypoglycemia &#40;repaglinide&#41;&#59; salt and fluid retention&#44; heart failure and fractures &#40;pioglitazone&#41;&#46;</p> <p id="spar0030" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">b</span> Empagliflozin&#44; canagliflozin and liraglutide have shown reduced cardiovascular morbidity and mortality in patients with high vascular risk type 2 diabetes&#46;</p> <p id="spar0035" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">c</span> Saxagliptin should be avoided for patients with heart failure&#46;</p> <p id="spar0040" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">d</span> Pioglitazone is contraindicated for patients with heart failure or at risk for fractures&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">We considered the presence of the frailty phenotype when the patient met 3 or more criteria and the prefrailty phenotype when 1 or 2 criteria were met&#46;</p><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviation</span>&#58; BMI&#44; body mass index&#46;</p><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Taken from Fried et al&#46;<a class="elsevierStyleCrossRef" href="#bib0935"><span class="elsevierStyleSup">2</span></a></p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Marker&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Assessment tool&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Spontaneous weight loss&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Unexplained loss &#62;4&#46;5<span class="elsevierStyleHsp" style=""></span>kg or &#62;5&#37; of the weight in the last year&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Fatigue&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Self-reported fatigue&#44; identified by a score &#62;2 on the Center Epidemiological Studies-Depression scale &#40;0&#8211;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Muscle weakness&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Grip strength &#40;dynamometer&#41; &#60;20&#37; of normal&#44; adjusted for BMI and sex&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Motor retardation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Gait speed for covering 4&#46;5<span class="elsevierStyleHsp" style=""></span>m &#60;20&#37; of normal&#44; adjusted for sex and height &#40;&#62;6&#8211;7<span class="elsevierStyleHsp" style=""></span>s&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Hypoactivity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Weekly calorie expenditure below the lower quintile&#44; adjusted for sex &#40;men &#60;383<span class="elsevierStyleHsp" style=""></span>kcal&#47;week&#44; women &#60;270<span class="elsevierStyleHsp" style=""></span>kcal&#47;week&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1678923.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Fried frailty criteria&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:185 [
            0 => array:3 [
              "identificador" => "bib0930"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Diabetes in older people&#58; new insights and remaining challenges"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S2213-8587(14)70176-7"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0935"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Frailty in older adults&#58; evidence for a phenotype"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0940"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:3 [
                  "comentario" => "Available from&#58; <span class="elsevierStyleInterRef" id="intr0015" href="http://www.unpopulation.org/">www&#46;unpopulation&#46;org</span> &#91;accessed 06&#46;11&#46;17&#93;"
                  "contribucion" => array:1 [
                    0 => array:1 [
                      "titulo" => "Population ageing and development"
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:1 [ …1]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0945"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Evoluci&#243;n de los indicadores de calidad asistencial al diab&#233;tico tipo 2 en atenci&#243;n primaria &#40;1996&#8211;2007&#41;"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [ …5]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0950"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prevalence of diabetes mellitus and impaired glucose regulation in Spain&#58; the Di&#64;bet&#46;es study"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00125-011-2336-9"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0955"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Federaci&#243;n Internacional de la Diabetes&#46; Atlas de la diabetes&#46; 6&#46;&#170; ed&#46; Actualizaci&#243;n&#59; 2014 &#91;accessed 11&#46;10&#46;17&#93;&#46; Available from&#58; <a href="http://www.idf.org/diabetesatlas">www&#46;idf&#46;org&#47;diabetesatlas</a>&#46;"
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0960"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A call for action in diabetes care for older people"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1464-5491.2011.03335.x"
                      "Revista" => array:7 [ …7]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0965"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:3 [
                  "comentario" => "134e1&#8211;e12"
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tratamiento de la diabetes tipo 2 en el paciente anciano"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [ …3]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0970"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Untangling the concepts of disability&#44; frailty&#44; and comorbidity&#58; implications for improved targeting and care"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0975"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Frailty as a major factor in the increased risk of death and disability in older people with diabetes"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jamda.2016.07.013"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0980"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Comparison of the prognostic importance of diagnosed diabetes&#44; co-morbidity and frailty in older people"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1464-5491.2010.02977.x"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0985"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Diabetes and risk of frailty and its potential mechanisms&#58; a prospective cohort study of older adults"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jamda.2015.04.008"
                      "Revista" => array:7 [ …7]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0990"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The third transition&#58; the clinical evolution oriented to the contemporary older patient"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jamda.2016.10.005"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0995"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Fragilidad&#58; &#191;de qu&#233; estamos hablando&#63; Implicaciones para la pr&#225;ctica cl&#237;nica diaria"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.regg.2017.04.004"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib1000"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The effect of comorbid illness and functional status on the expected benefits of intensive glucose control in older patients with type 2 diabetes&#58; a decision analysis"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib1005"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The risks and benefits of implementing glycemic control guidelines in frail older adults with diabetes mellitus"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1532-5415.2011.03362.x"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib1010"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Glycemic control and functional decline in nursing home residents with diabetes"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/jamainternmed.2016.6949"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib1015"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "SGS&#58; a structured treatment and teaching programme for older patients with diabetes mellitus&#8212;a prospective randomised controlled multi-centre trial"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/ageing/afp056"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib1020"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Incidence and care-related costs of severe hypoglycaemia requiring emergency treatment in Andalusia &#40;Spain&#41;&#58; the PAUEPAD project"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/dme.12843"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib1025"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The frequency and impact of hypoglycemia among hospitalized patients with diabetes&#58; a population-based study"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [ …5]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib1030"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Potential overtreatment of diabetes mellitus in older adults with tight glycemic control"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/jamainternmed.2014.7345"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib1035"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inadequate glycaemic control and therapeutic management of adults over 65 years old with type 2 diabetes mellitus in Spain"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s12603-017-0869-4"
                      "Revista" => array:2 [ …2]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib1040"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Emergency hospitalizations for adverse drug events in older Americans"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMsa1103053"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib1045"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hypoglycemia unawareness in older compared with middle-aged patients with type 2 diabetes"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2337/dc09-0114"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib1050"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Frequent hypoglycemia among elderly patients with poor glycemic control"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/archinternmed.2010.539"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib1055"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Severe hypoglycaemia and cognitive impairment in older patients with diabetes&#58; the Fremantle Diabetes Study"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00125-009-1437-1"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib1060"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "National estimates of insulin-related hypoglycemia and errors leading to emergency department visits and hospitalizations"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/jamainternmed.2014.136"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib1065"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "National trends in US hospital admissions for hyperglycemia and hypoglycemia among Medicare beneficiaries&#44; 1999 to 2011"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/jamainternmed.2014.1824"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib1070"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Relationship between hypoglycemic episodes and ventricular arrhythmias in patients with type 2 diabetes and cardiovascular diseases&#58; silent hypoglycemias and silent arrhythmias"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2337/dc13-0600"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib1075"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "New IDF Guideline for managing type 2 diabetes in older people"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.diabres.2014.03.005"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib1080"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "11&#46; Older adults"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2337/dc17-S014"
                      "Revista" => array:7 [ …7]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib1085"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Glycemic control&#44; complications&#44; and death in older diabetic patients&#58; the diabetes and aging study"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2337/dc10-2377"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib1090"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "An approach to diabetes mellitus in hospice and palliative medicine"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1089/jpm.2010.0191"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib1095"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "An evaluation of the effectiveness of a multi-modal intervention in frail and pre-frail older people with type 2 diabetes&#8212;the MID-Frail study&#58; study protocol for a randomised controlled trial"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/1745-6215-15-34"
                      "Revista" => array:5 [ …5]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib1100"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The look AHEAD study&#58; implications for clinical practice go beyond the headlines"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jand.2014.01.008"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            35 => array:3 [
              "identificador" => "bib1105"
              "etiqueta" => "36"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Intensive weight loss intervention in older individuals&#58; results from the Action for Health in Diabetes Type 2 diabetes mellitus trial"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/jgs.12271"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            36 => array:3 [
              "identificador" => "bib1110"
              "etiqueta" => "37"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Aging and physical function in type 2 diabetes&#58; 8 years of an intensive lifestyle intervention"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/gerona/glu083"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            37 => array:3 [
              "identificador" => "bib1115"
              "etiqueta" => "38"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Nutrition education improves metabolic outcomes among older adults with diabetes mellitus&#58; results from a randomized controlled trial"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1006/pmed.2001.0985"
                      "Revista" => array:7 [ …7]
                    ]
                  ]
                ]
              ]
            ]
            38 => array:3 [
              "identificador" => "bib1120"
              "etiqueta" => "39"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The effect of diabetes mellitus on age-associated lean mass loss in 3153 older adults"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1464-5491.2010.03118.x"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            39 => array:3 [
              "identificador" => "bib1125"
              "etiqueta" => "40"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Fat infiltration of muscle&#44; diabetes&#44; and clinical fracture risk in older adults"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1210/jc.2010-0780"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            40 => array:3 [
              "identificador" => "bib1130"
              "etiqueta" => "41"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Diabetes and exercise in the elderly"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1159/000357342"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            41 => array:3 [
              "identificador" => "bib1135"
              "etiqueta" => "42"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Lessened decline in physical activity and impairment of older adults with diabetes with telemedicine and pedometer use&#58; results from the IDEATel study"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/ageing/afq147"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            42 => array:3 [
              "identificador" => "bib1140"
              "etiqueta" => "43"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Short-term aerobic exercise reduces arterial stiffness in older adults with type 2 diabetes&#44; hypertension&#44; and hypercholesterolemia"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            43 => array:3 [
              "identificador" => "bib1145"
              "etiqueta" => "44"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            44 => array:3 [
              "identificador" => "bib1150"
              "etiqueta" => "45"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:1 [ …1]
                  ]
                ]
              ]
            ]
            45 => array:3 [
              "identificador" => "bib1155"
              "etiqueta" => "46"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:1 [ …1]
                  ]
                ]
              ]
            ]
            46 => array:3 [
              "identificador" => "bib1160"
              "etiqueta" => "47"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:1 [ …1]
                  ]
                ]
              ]
            ]
            47 => array:3 [
              "identificador" => "bib1165"
              "etiqueta" => "48"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            48 => array:3 [
              "identificador" => "bib1170"
              "etiqueta" => "49"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            49 => array:3 [
              "identificador" => "bib1175"
              "etiqueta" => "50"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            50 => array:3 [
              "identificador" => "bib1180"
              "etiqueta" => "51"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            51 => array:3 [
              "identificador" => "bib1185"
              "etiqueta" => "52"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            52 => array:3 [
              "identificador" => "bib1190"
              "etiqueta" => "53"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            53 => array:3 [
              "identificador" => "bib1195"
              "etiqueta" => "54"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            54 => array:3 [
              "identificador" => "bib1200"
              "etiqueta" => "55"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            55 => array:3 [
              "identificador" => "bib1205"
              "etiqueta" => "56"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            56 => array:3 [
              "identificador" => "bib1210"
              "etiqueta" => "57"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            57 => array:3 [
              "identificador" => "bib1215"
              "etiqueta" => "58"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:1 [ …1]
                  ]
                ]
              ]
            ]
            58 => array:3 [
              "identificador" => "bib1220"
              "etiqueta" => "59"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            59 => array:3 [
              "identificador" => "bib1225"
              "etiqueta" => "60"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            60 => array:3 [
              "identificador" => "bib1230"
              "etiqueta" => "61"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            61 => array:3 [
              "identificador" => "bib1235"
              "etiqueta" => "62"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:1 [ …1]
                  ]
                ]
              ]
            ]
            62 => array:3 [
              "identificador" => "bib1240"
              "etiqueta" => "63"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:1 [ …1]
                  ]
                ]
              ]
            ]
            63 => array:3 [
              "identificador" => "bib1245"
              "etiqueta" => "64"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            64 => array:3 [
              "identificador" => "bib1250"
              "etiqueta" => "65"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:1 [ …1]
                  ]
                ]
              ]
            ]
            65 => array:3 [
              "identificador" => "bib1255"
              "etiqueta" => "66"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            66 => array:3 [
              "identificador" => "bib1260"
              "etiqueta" => "67"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            67 => array:3 [
              "identificador" => "bib1265"
              "etiqueta" => "68"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            68 => array:3 [
              "identificador" => "bib1270"
              "etiqueta" => "69"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:1 [ …1]
                  ]
                ]
              ]
            ]
            69 => array:3 [
              "identificador" => "bib1275"
              "etiqueta" => "70"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            70 => array:3 [
              "identificador" => "bib1280"
              "etiqueta" => "71"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:1 [ …1]
                  ]
                ]
              ]
            ]
            71 => array:3 [
              "identificador" => "bib1285"
              "etiqueta" => "72"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:1 [ …1]
                  ]
                ]
              ]
            ]
            72 => array:3 [
              "identificador" => "bib1290"
              "etiqueta" => "73"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            73 => array:3 [
              "identificador" => "bib1295"
              "etiqueta" => "74"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            74 => array:3 [
              "identificador" => "bib1300"
              "etiqueta" => "75"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            75 => array:3 [
              "identificador" => "bib1305"
              "etiqueta" => "76"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:1 [ …1]
                  ]
                ]
              ]
            ]
            76 => array:3 [
              "identificador" => "bib1310"
              "etiqueta" => "77"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            77 => array:3 [
              "identificador" => "bib1315"
              "etiqueta" => "78"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            78 => array:3 [
              "identificador" => "bib1320"
              "etiqueta" => "79"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            79 => array:3 [
              "identificador" => "bib1325"
              "etiqueta" => "80"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            80 => array:3 [
              "identificador" => "bib1330"
              "etiqueta" => "81"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            81 => array:3 [
              "identificador" => "bib1335"
              "etiqueta" => "82"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:1 [ …1]
                  ]
                ]
              ]
            ]
            82 => array:3 [
              "identificador" => "bib1340"
              "etiqueta" => "83"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            83 => array:3 [
              "identificador" => "bib1345"
              "etiqueta" => "84"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            84 => array:3 [
              "identificador" => "bib1350"
              "etiqueta" => "85"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:1 [ …1]
                  ]
                ]
              ]
            ]
            85 => array:3 [
              "identificador" => "bib1355"
              "etiqueta" => "86"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            86 => array:3 [
              "identificador" => "bib1360"
              "etiqueta" => "87"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:1 [ …1]
                  ]
                ]
              ]
            ]
            87 => array:3 [
              "identificador" => "bib1365"
              "etiqueta" => "88"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            88 => array:3 [
              "identificador" => "bib1370"
              "etiqueta" => "89"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            89 => array:3 [
              "identificador" => "bib1375"
              "etiqueta" => "90"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            90 => array:3 [
              "identificador" => "bib1380"
              "etiqueta" => "91"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            91 => array:3 [
              "identificador" => "bib1385"
              "etiqueta" => "92"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            92 => array:3 [
              "identificador" => "bib1390"
              "etiqueta" => "93"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            93 => array:3 [
              "identificador" => "bib1395"
              "etiqueta" => "94"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            94 => array:3 [
              "identificador" => "bib1400"
              "etiqueta" => "95"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:1 [ …1]
                  ]
                ]
              ]
            ]
            95 => array:3 [
              "identificador" => "bib1405"
              "etiqueta" => "96"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            96 => array:3 [
              "identificador" => "bib1410"
              "etiqueta" => "97"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            97 => array:3 [
              "identificador" => "bib1415"
              "etiqueta" => "98"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            98 => array:3 [
              "identificador" => "bib1420"
              "etiqueta" => "99"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            99 => array:3 [
              "identificador" => "bib1425"
              "etiqueta" => "100"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            100 => array:3 [
              "identificador" => "bib1430"
              "etiqueta" => "101"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            101 => array:3 [
              "identificador" => "bib1435"
              "etiqueta" => "102"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            102 => array:3 [
              "identificador" => "bib1440"
              "etiqueta" => "103"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            103 => array:3 [
              "identificador" => "bib1445"
              "etiqueta" => "104"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            104 => array:3 [
              "identificador" => "bib1450"
              "etiqueta" => "105"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            105 => array:3 [
              "identificador" => "bib1455"
              "etiqueta" => "106"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            106 => array:3 [
              "identificador" => "bib1460"
              "etiqueta" => "107"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            107 => array:3 [
              "identificador" => "bib1465"
              "etiqueta" => "108"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            108 => array:3 [
              "identificador" => "bib1470"
              "etiqueta" => "109"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            109 => array:3 [
              "identificador" => "bib1475"
              "etiqueta" => "110"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            110 => array:3 [
              "identificador" => "bib1480"
              "etiqueta" => "111"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            111 => array:3 [
              "identificador" => "bib1485"
              "etiqueta" => "112"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            112 => array:3 [
              "identificador" => "bib1490"
              "etiqueta" => "113"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            113 => array:3 [
              "identificador" => "bib1495"
              "etiqueta" => "114"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            114 => array:3 [
              "identificador" => "bib1500"
              "etiqueta" => "115"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            115 => array:3 [
              "identificador" => "bib1505"
              "etiqueta" => "116"
              "referencia" => array:1 [
                0 => array:3 [
                  "comentario" => "pii&#58;S2213-1779&#58;30535-8"
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            116 => array:3 [
              "identificador" => "bib1510"
              "etiqueta" => "117"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            117 => array:3 [
              "identificador" => "bib1515"
              "etiqueta" => "118"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            118 => array:3 [
              "identificador" => "bib1520"
              "etiqueta" => "119"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            119 => array:3 [
              "identificador" => "bib1525"
              "etiqueta" => "120"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            120 => array:3 [
              "identificador" => "bib1530"
              "etiqueta" => "121"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            121 => array:3 [
              "identificador" => "bib1535"
              "etiqueta" => "122"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            122 => array:3 [
              "identificador" => "bib1540"
              "etiqueta" => "123"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            123 => array:3 [
              "identificador" => "bib1545"
              "etiqueta" => "124"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            124 => array:3 [
              "identificador" => "bib1550"
              "etiqueta" => "125"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            125 => array:3 [
              "identificador" => "bib1555"
              "etiqueta" => "126"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            126 => array:3 [
              "identificador" => "bib1560"
              "etiqueta" => "127"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            127 => array:3 [
              "identificador" => "bib1565"
              "etiqueta" => "128"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            128 => array:3 [
              "identificador" => "bib1570"
              "etiqueta" => "129"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            129 => array:3 [
              "identificador" => "bib1575"
              "etiqueta" => "130"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            130 => array:3 [
              "identificador" => "bib1580"
              "etiqueta" => "131"
              "referencia" => array:1 [
                0 => array:3 [
                  "comentario" => "CD006423"
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            131 => array:3 [
              "identificador" => "bib1585"
              "etiqueta" => "132"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            132 => array:3 [
              "identificador" => "bib1590"
              "etiqueta" => "133"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            133 => array:3 [
              "identificador" => "bib1595"
              "etiqueta" => "134"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            134 => array:3 [
              "identificador" => "bib1600"
              "etiqueta" => "135"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            135 => array:3 [
              "identificador" => "bib1605"
              "etiqueta" => "136"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            136 => array:3 [
              "identificador" => "bib1610"
              "etiqueta" => "137"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            137 => array:3 [
              "identificador" => "bib1615"
              "etiqueta" => "138"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            138 => array:3 [
              "identificador" => "bib1620"
              "etiqueta" => "139"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            139 => array:3 [
              "identificador" => "bib1625"
              "etiqueta" => "140"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            140 => array:3 [
              "identificador" => "bib1630"
              "etiqueta" => "141"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            141 => array:3 [
              "identificador" => "bib1635"
              "etiqueta" => "142"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            142 => array:3 [
              "identificador" => "bib1640"
              "etiqueta" => "143"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            143 => array:3 [
              "identificador" => "bib1645"
              "etiqueta" => "144"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            144 => array:3 [
              "identificador" => "bib1650"
              "etiqueta" => "145"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            145 => array:3 [
              "identificador" => "bib1655"
              "etiqueta" => "146"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            146 => array:3 [
              "identificador" => "bib1660"
              "etiqueta" => "147"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            147 => array:3 [
              "identificador" => "bib1665"
              "etiqueta" => "148"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            148 => array:3 [
              "identificador" => "bib1670"
              "etiqueta" => "149"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            149 => array:3 [
              "identificador" => "bib1675"
              "etiqueta" => "150"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            150 => array:3 [
              "identificador" => "bib1680"
              "etiqueta" => "151"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            151 => array:3 [
              "identificador" => "bib1685"
              "etiqueta" => "152"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            152 => array:3 [
              "identificador" => "bib1690"
              "etiqueta" => "153"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            153 => array:3 [
              "identificador" => "bib1695"
              "etiqueta" => "154"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:1 [ …1]
                  ]
                ]
              ]
            ]
            154 => array:3 [
              "identificador" => "bib1700"
              "etiqueta" => "155"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            155 => array:3 [
              "identificador" => "bib1705"
              "etiqueta" => "156"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            156 => array:3 [
              "identificador" => "bib1710"
              "etiqueta" => "157"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            157 => array:3 [
              "identificador" => "bib1715"
              "etiqueta" => "158"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            158 => array:3 [
              "identificador" => "bib1720"
              "etiqueta" => "159"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:1 [ …1]
                  ]
                ]
              ]
            ]
            159 => array:3 [
              "identificador" => "bib1725"
              "etiqueta" => "160"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            160 => array:3 [
              "identificador" => "bib1730"
              "etiqueta" => "161"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            161 => array:3 [
              "identificador" => "bib1735"
              "etiqueta" => "162"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            162 => array:3 [
              "identificador" => "bib1740"
              "etiqueta" => "163"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            163 => array:3 [
              "identificador" => "bib1745"
              "etiqueta" => "164"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            164 => array:3 [
              "identificador" => "bib1750"
              "etiqueta" => "165"
              "referencia" => array:1 [
                0 => array:3 [
                  "comentario" => "CD005613"
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:1 [ …1]
                  ]
                ]
              ]
            ]
            165 => array:3 [
              "identificador" => "bib1755"
              "etiqueta" => "166"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            166 => array:3 [
              "identificador" => "bib1760"
              "etiqueta" => "167"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            167 => array:3 [
              "identificador" => "bib1765"
              "etiqueta" => "168"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            168 => array:3 [
              "identificador" => "bib1770"
              "etiqueta" => "169"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            169 => array:3 [
              "identificador" => "bib1775"
              "etiqueta" => "170"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            170 => array:3 [
              "identificador" => "bib1780"
              "etiqueta" => "171"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            171 => array:3 [
              "identificador" => "bib1785"
              "etiqueta" => "172"
              "referencia" => array:1 [
                0 => array:3 [
                  "comentario" => "CD003287"
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:1 [ …1]
                  ]
                ]
              ]
            ]
            172 => array:3 [
              "identificador" => "bib1790"
              "etiqueta" => "173"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            173 => array:3 [
              "identificador" => "bib1795"
              "etiqueta" => "174"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            174 => array:3 [
              "identificador" => "bib1800"
              "etiqueta" => "175"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            175 => array:3 [
              "identificador" => "bib1805"
              "etiqueta" => "176"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            176 => array:3 [
              "identificador" => "bib1810"
              "etiqueta" => "177"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:1 [ …1]
                  ]
                ]
              ]
            ]
            177 => array:3 [
              "identificador" => "bib1815"
              "etiqueta" => "178"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:1 [ …1]
                  ]
                ]
              ]
            ]
            178 => array:3 [
              "identificador" => "bib1820"
              "etiqueta" => "179"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            179 => array:3 [
              "identificador" => "bib1825"
              "etiqueta" => "180"
              "referencia" => array:1 [
                0 => array:3 [
                  "comentario" => "&#91;Epub ahead of print&#93;"
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            180 => array:3 [
              "identificador" => "bib1830"
              "etiqueta" => "181"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            181 => array:3 [
              "identificador" => "bib1835"
              "etiqueta" => "182"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            182 => array:3 [
              "identificador" => "bib1840"
              "etiqueta" => "183"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            183 => array:3 [
              "identificador" => "bib1845"
              "etiqueta" => "184"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:2 [ …2]
                  ]
                ]
              ]
            ]
            184 => array:3 [
              "identificador" => "bib1850"
              "etiqueta" => "185"
              "referencia" => array:1 [
                0 => array:3 [
                  "comentario" => "85e1-10"
                  "contribucion" => array:1 [
                    0 => array:2 [ …2]
                  ]
                  "host" => array:1 [
                    0 => array:1 [ …1]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/22548874/0000021800000002/v1_201802230423/S2254887418300122/v1_201802230423/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "3982"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Special Article"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/22548874/0000021800000002/v1_201802230423/S2254887418300122/v1_201802230423/en/main.pdf?idApp=WRCEE&text.app=https://revclinesp.es/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2254887418300122?idApp=WRCEE"
]
Article information
ISSN: 22548874
Original language: English
The statistics are updated each day
Year/Month Html Pdf Total
2024 November 4 0 4
2024 October 81 0 81
2024 September 79 2 81
2024 August 106 4 110
2024 July 56 4 60
2024 June 26 0 26
2024 May 25 1 26
2024 April 50 0 50
2024 March 48 3 51
2024 February 39 0 39
2024 January 26 0 26
2023 December 65 12 77
2023 November 66 7 73
2023 October 50 12 62
2023 September 36 3 39
2023 August 41 8 49
2023 July 24 1 25
2023 June 21 2 23
2023 May 17 3 20
2023 April 20 3 23
2023 March 25 3 28
2023 February 23 0 23
2023 January 29 0 29
2022 December 31 0 31
2022 November 26 0 26
2022 October 34 3 37
2022 September 28 0 28
2022 August 28 2 30
2022 July 22 3 25
2022 June 13 0 13
2022 May 21 5 26
2022 April 9 2 11
2022 March 23 2 25
2022 February 16 2 18
2022 January 17 0 17
2021 December 10 0 10
2021 November 4 0 4
2018 November 5 2 7
2018 March 0 1 1
2018 February 0 1 1
Show all

Follow this link to access the full text of the article

Idiomas
Revista Clínica Española (English Edition)
es en

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?