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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Background</span><p id="par0005" class="elsevierStylePara elsevierViewall">Heart failure &#40;HF&#41; is a major&#44; worldwide epidemiological problem due to its high associated mortality and morbidity<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">1</span></a> and considerable consumption of healthcare resources&#44; especially by elderly patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">2&#44;3</span></a> Type 2 diabetes mellitus &#40;DM2&#41; for its part has increased in prevalence&#44; with the number of individuals with diabetes quadrupling in the last 30 years and becoming the ninth leading cause of death&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">4</span></a> DM2 is a disease that is closely linked to obesity&#44; and its prevalence increases markedly with age&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">5</span></a> Therefore&#44; the combined diagnoses of DM2 and HF in individual patients has seen an exponential increase&#46;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">6&#44;7</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Patients with HF have a 4-fold greater rate of DM2 &#40;20&#37;&#41; than patients without HF &#40;4&#8211;6&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">8</span></a> In patients hospitalized for HF&#44; the proportion of DM2 cases increases up to 40&#37; and even further in the internal medicine setting &#40;45&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">9</span></a> Moreover&#44; patients with DM2 have a 75&#37; greater risk of cardiovascular death&#44; which generally develops early &#40;mean of 14&#46;6 years earlier&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">4</span></a> The risk of developing HF is also multiplied 2&#46;5-fold for patients with DM2&#44;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">10</span></a> and hospitalization for HF is increased in patients with diabetes compared with those without DM2&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">6</span></a> In patients with asymptomatic left ventricular systolic dysfunction&#44; DM2 is associated with a greater risk of developing HF&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">11</span></a> Authors have also suggested that HF increases the risk of developing DM2 and is related to HF severity &#40;defined by the daily dose of loop diuretics&#41; and the risk of developing DM2&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">12</span></a> There is therefore a two-way association between HF and DM2&#46;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">6&#44;7&#44;13</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Clinical implications of the coexistence of heart failure and type 2 diabetes mellitus</span><p id="par0015" class="elsevierStylePara elsevierViewall">In terms of symptoms&#44; patients with DM2 have a poorer New York Heart Association functional class and more HR-related signs and symptoms than patients without DM2&#44; 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there is a diabetic cardiomyopathy that differs from the ischemic and hypertensive&#44; which is secondary to the direct effects of the metabolic disorders of DM2 on myocardial function &#40;microangiopathic&#44; mitochondrial energy metabolism disorders&#44; structural dysfunction&#41;&#46; DM2 mainly aggravates the diastolic dysfunction in HF&#44; increasing stiffness and left ventricular volume&#46; The diagnosis of diabetic cardiomyopathy requires a history of DM2 that has progressed for years&#44; poor metabolic control and ruling out other causes&#46;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">6&#44;7&#44;13</span></a> Two phenotypes have been described&#59; initially&#44; reports indicated that the phenotype was dilated&#44; especially in patients with microvascular disease&#46; Subsequently&#44; there was a greater tendency to consider the phenotype restrictive in women with obesity and poor DM control&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">6</span></a> The mechanisms by which DM2 affects the left ventricle differ between HFpEF and HFrEF&#46; Hyperglycemia&#44; hyperinsulinemia and lipotoxicity predispose patients to myocardial restriction&#44; and autoimmunity predisposes patients to dilated cardiomyopathy&#46; Endothelial dysfunction in the coronary microvasculature predominates in HFpEF and is triggered by the comorbidity-related inflammation&#44; while the loss of cardiomyocytes due to ischemia or toxic agents predominates in HFrEF&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">6</span></a> Interstitial and perivascular myocardial fibrosis also seem to play a role&#44; as does the increased production of advanced glycosylation end products&#44; increasing collagen stiffness and with it the diastolic stiffness in diabetic cardiomyopathy&#46; The presence of fibrosis&#44; although relevant for both phenotypes&#44; appears to be more significant in dilated HF&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">6</span></a> Autonomic neuropathy and calcium homeostasis disorders can also be a nexus between DM2 and the onset of HF&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">13</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">How and with what should diabetes mellitus be treated in patients with heart failure&#63;</span><p id="par0025" class="elsevierStylePara elsevierViewall">Gradual glycemic control should be implemented for patients with DM and HF&#44; giving preference to drugs that have been shown to be safe and effective&#44;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">16</span></a> such as metformin&#44; without overlooking appropriate diets and exercise&#46; Contrary to earlier assumptions&#44; metformin is safe for patients with HF and is therefore also the treatment of choice for patients with DM and HF&#44; although renal function should always be monitored&#44; given that metformin is contraindicated for patients with advanced renal or hepatic failure due to the risk of lactic acidosis&#46; There are retrospective and cohort studies with metformin that have suggested a reduction in cardiovascular morbidity and mortality in patients with diabetes with or without HF&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">6</span></a> However&#44; there are no studies that have shown the safety of sulfonylureas in patients with HF&#59; sulfonylureas are therefore not recommended for general use&#46;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">6&#44;7</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">In terms of glitazones&#44; the peroxisome proliferator-activated receptor gamma agonist effect could be beneficial for diastolic dysfunction&#59; however&#44; glitazones cause fluid retention and can therefore worsen the HF or increase the rate of new cases of HF&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">6</span></a> Clinical practice registries and cardiovascular safety studies have shown the neutrality of incretin mimetics when administered to patients with HF&#46; A study with 1&#44;499&#44;650 patients&#44; 29&#44;741 of whom were hospitalized for HF&#47;year&#44; reported that the hospitalization rates for HF did not increase with the use of drugs based on incretin therapies compared with patients administered metformin and&#47;or sulfonylureas&#46; This effect did not occur either in patients with a history of HF or those who had no history of HF&#46; The results for HF were similar for dipeptidyl peptidase-4 inhibitors and glucagon-like peptide 1 analogs &#40;GLP-1&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">17</span></a> A number of GLP-1 analogs&#44; such as liraglutide and semaglutide&#44; have however shown a reduction in cardiovascular events&#46; In the SAVOR-TIMI 53 study&#44; saxagliptin did increase the rate of hospitalization for HF for patients with at least 2 other additional risk factors&#58; a glomerular filtration rate &#8804;60<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;m<span class="elsevierStyleSup">2</span>&#44; a higher amino-terminal fragment of the brain natriuretic peptide concentration &#40;&#62;332<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&#41; and previous HF&#46;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">6&#44;7&#44;18</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">One family of hypoglycemic agents that has shown major results in HF is that of the sodium-glucose cotransporter-2 &#40;SGLT2&#41; inhibitors&#46; The pivotal study with empagliflozin &#40;EMPAREG-OUTCOME&#41; showed a 35&#37; reduction in the relative risk &#40;RR&#41; of hospitalization for HF &#40;HR&#44; 0&#46;65&#59; 95&#37; CI 0&#46;50&#8211;0&#46;85&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;002&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">19</span></a> These results were independent of HbA1c levels before and during the study&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">20</span></a> A post hoc analysis showed a combined reduction in hospitalizations for HF and cardiovascular mortality&#44; regardless of the HF treatment&#46; However&#44; this benefit was mainly observed in the patients with no prior history of HF&#44; i&#46;e&#46;&#44; incident HF&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">21</span></a> The CANVAS study &#40;canagliflozin&#41; also observed a reduction in hospitalizations for HF &#40;HR&#44; 0&#46;67&#59; 95&#37; CI 0&#46;52&#8211;0&#46;87&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">22</span></a> When the HF data were analyzed&#44; canagliflozin was observed to reduce the number of hospitalizations for HF and the rate of cardiovascular death&#59; however&#44; these benefits were greater in the patients with a prior history of HF&#46; Recently&#44; the DECLARE-TIME 58<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">23</span></a> study with dapagliflozin confirmed the beneficial effect of SGLT2 inhibitors on hospitalizations for HF&#44; suggesting the presence of a class effect for HF&#46; An important aspect to consider is that the prevalence of HF established in these studies was relatively low&#46; The percentage of patients with HF at the start of the study was 10&#37; for EMPA-REG&#44; 11&#46;9&#37; for CANVAS and 9&#46;9&#37; for DECLARE&#46; Thus&#44; the evidence on the benefit of these drugs for patients with established HF is still weak&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Research is ongoing into the pathophysiological mechanisms of SGLT2 inhibitors that can explain the inhibitors&#8217; effects and whether their protective effect in HF is only for patients with diabetes or is generalizable to patients without DM&#46; There are clinical trials underway with patients without diabetes that should provide answers to these topics&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">In DM2&#44; the use of insulin is usually a marker of the long-term nature and severity of the DM and cannot therefore be directly related to adverse cardiovascular events&#46; Although insulin increases myocardial blood flow&#44; it decreases the heart rate and slightly improves the cardiac output&#46; Insulin is a hormone with a high sodium retention capacity and when combined with reduced glycosuria can exacerbate fluid retention and worsen the HF&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">24</span></a> Nevertheless&#44; insulin&#39;s safety has been demonstrated in studies with new insulins&#46; Thus&#44; the safety of insulin glargine was demonstrated with the publication of the ORIGIN study&#44; which observed no increase in hospitalizations for HF&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">25</span></a> Likewise&#44; insulin degludec showed its noninferiority versus insulin glargine in preventing cardiovascular events&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">26</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Treatment of heart failure in patients with type 2 diabetes mellitus</span><p id="par0050" class="elsevierStylePara elsevierViewall">In terms of HF treatment for patients with DM2&#44; there are no specific differences in the guidelines compared with patient without diabetes&#46; In the clinical trials&#44; all drugs and devices for HF were equally effective&#44; regardless of whether the patients had DM or not&#46; To date&#44; clinical trials have not been conducted on HF treatment that include only patients with DM2&#44; and the available evidence is derived from subanalyses of mixed populations&#46;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">6&#44;7</span></a> There have been intriguing reports that the dual inhibition of the renin&#8211;angiotensin system and neprilysin could lead to better glycemic control&#44; given that neprilysin contributes to the degradation of endogenous GLP-1&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">27</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusion</span><p id="par0055" class="elsevierStylePara elsevierViewall">In summary&#44; HF and diabetes coexist in many patients with a pathophysiological mechanism that favors the conditions&#46; For patients with diabetes and HF&#44; there are drugs such as SGLT2 inhibitors for treating DM&#44; with excellent cardiovascular safety profiles and that help reduce cardiac readmissions&#46; In terms of the future&#44; it would be of great interest to know the results of ongoing studies designed specifically for this goal<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">28</span></a> and that even include patients without DM2&#46;</p></span></span>"
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        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Background"
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        5 => array:2 [
          "identificador" => "sec0010"
          "titulo" => "Clinical implications of the coexistence of heart failure and type 2 diabetes mellitus"
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        6 => array:2 [
          "identificador" => "sec0015"
          "titulo" => "Pathophysiological implications of the coexistence of heart failure and type 2 diabetes mellitus"
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          "identificador" => "sec0020"
          "titulo" => "How and with what should diabetes mellitus be treated in patients with heart failure&#63;"
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          "identificador" => "sec0025"
          "titulo" => "Treatment of heart failure in patients with type 2 diabetes mellitus"
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        9 => array:2 [
          "identificador" => "sec0030"
          "titulo" => "Conclusion"
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        10 => array:1 [
          "titulo" => "References"
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    "fechaRecibido" => "2018-12-17"
    "fechaAceptado" => "2019-01-08"
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          "clase" => "keyword"
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            0 => "Heart failure"
            1 => "Type 2 diabetes mellitus"
            2 => "SGLT2 inhibitors"
          ]
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          "clase" => "keyword"
          "titulo" => "Palabras clave"
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          "palabras" => array:3 [
            0 => "Insuficiencia cardiaca"
            1 => "Diabetes mellitus tipo 2"
            2 => "Inhibidores SGLT2"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">There is a bidirectional association between heart failure &#40;HF&#41; and type 2 diabetes mellitus &#40;DM2&#41;&#44; which has resulted in an exponential increase in the combination of the 2 diseases in a single patient&#46; This combination is one of many common causes that lead to the pathophysiological pathways resulting in the deleterious effect of DM2 on HF&#46; The inevitable clinical consequence is that&#44; when faced with this situation&#44; patients present worse symptoms and a poorer prognosis than patients with HF but without DM2&#46;</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">We should therefore consider how to treat DM2 in patients with HF and how to treat HF in patients with DM2&#46; In this review&#44; we highlight the latest published data on this issue&#46;</p></span>"
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      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Existe una asociaci&#243;n bidireccional entre la insuficiencia cardiaca &#40;IC&#41; y la diabetes mellitus tipo 2 &#40;DM2&#41; que hace que la combinaci&#243;n de ambas enfermedades en un mismo paciente haya pasado a tener un incremento exponencial&#46; Dicha combinaci&#243;n&#44; parte de m&#250;ltiples causas comunes que llevan a v&#237;as fisiopatol&#243;gicas que resultan en un efecto delet&#233;reo de la DM2 sobre la IC&#46; La consecuencia cl&#237;nica inevitable es que ante dicha situaci&#243;n el paciente presente peor cl&#237;nica y peor pron&#243;stico que el paciente con IC sin DM2&#46;</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Por todo ello debemos tener en cuenta c&#243;mo tratar la DM2 en pacientes con IC&#44; y c&#243;mo tratar la IC en pacientes con DM2&#46; En esta revisi&#243;n se hace hincapi&#233; en los &#250;ltimos datos publicados al respecto&#46;</p></span>"
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      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Formiga F&#44; Camafort M&#44; Carrasco S&#225;nchez FJ&#46; Insuficiencia cardiaca y diabetes&#58; la confrontaci&#243;n de dos grandes epidemias del siglo <span class="elsevierStyleSmallCaps">xxi</span>&#46; Rev Clin Esp&#46; 2020&#59;220&#58;135&#8211;138&#46;</p>"
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      "titulo" => "References"
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                            0 => "Y&#46; Zheng"
                            1 => "S&#46;H&#46; Ley"
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                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
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                            0 => "R&#46; G&#243;mez-Huelgas"
                            1 => "F&#46; G&#243;mez Peralta"
                            2 => "L&#46; Rodr&#237;guez Ma&#241;as"
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                          ]
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                      "doi" => "10.1016/j.regg.2017.12.003"
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                        "tituloSerie" => "Rev Esp Geriatr Gerontol"
                        "fecha" => "2018"
                        "volumen" => "53"
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29439834"
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              "identificador" => "bib0170"
              "etiqueta" => "6"
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                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Heart failure and diabetes&#58; metabolic alterations and therapeutic interventions&#58; a state-of-the-art review from the Translational Research Committee of the Heart Failure Association-European Society of Cardiology"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46; Maack"
                            1 => "M&#46; Lehrke"
                            2 => "J&#46; Backs"
                            3 => "F&#46;R&#46; Heinzel"
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                          ]
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                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Heart J"
                        "fecha" => "2018"
                        "volumen" => "39"
                        "paginaInicial" => "4243"
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                      "titulo" => "Type 2 diabetes mellitus and heart failure&#58; a position statement from the Heart Failure Association of the European Society of Cardiology"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
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                            0 => "P&#46;M&#46; Seferovi&#263;"
                            1 => "M&#46;C&#46; Petrie"
                            2 => "G&#46;S&#46; Filippatos"
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Vol. 220. Issue 2.
Pages 135-138 (March 2020)
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Vol. 220. Issue 2.
Pages 135-138 (March 2020)
Review
Heart failure and diabetes: The confrontation of two major epidemics of the 21st century
Insuficiencia cardiaca y diabetes: la confrontación de dos grandes epidemias del siglo xxi
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7
F. Formigaa, M. Camafortb,
Corresponding author
camafort@clinic.ub.es

Corresponding author.
, F.J. Carrasco Sánchezc,d
a Servicio de Medicina Interna, Hospital Universitario de Bellvitge, IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain
b Servicio de Medicina Interna, Hospital Clínic, IDIBAPS, Universidad de Barcelona, Barcelona, Spain
c Unidad de Gestión Clínica de Medicina Interna y Cuidados Paliativos, Hospital Universitario Juan Ramón Jimenez, Huelva, Spain
d Grupo de Trabajo Diabetes, Obesidad y Nutrición de la Sociedad Española de Medicina Interna
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Abstract

There is a bidirectional association between heart failure (HF) and type 2 diabetes mellitus (DM2), which has resulted in an exponential increase in the combination of the 2 diseases in a single patient. This combination is one of many common causes that lead to the pathophysiological pathways resulting in the deleterious effect of DM2 on HF. The inevitable clinical consequence is that, when faced with this situation, patients present worse symptoms and a poorer prognosis than patients with HF but without DM2.

We should therefore consider how to treat DM2 in patients with HF and how to treat HF in patients with DM2. In this review, we highlight the latest published data on this issue.

Keywords:
Heart failure
Type 2 diabetes mellitus
SGLT2 inhibitors
Resumen

Existe una asociación bidireccional entre la insuficiencia cardiaca (IC) y la diabetes mellitus tipo 2 (DM2) que hace que la combinación de ambas enfermedades en un mismo paciente haya pasado a tener un incremento exponencial. Dicha combinación, parte de múltiples causas comunes que llevan a vías fisiopatológicas que resultan en un efecto deletéreo de la DM2 sobre la IC. La consecuencia clínica inevitable es que ante dicha situación el paciente presente peor clínica y peor pronóstico que el paciente con IC sin DM2.

Por todo ello debemos tener en cuenta cómo tratar la DM2 en pacientes con IC, y cómo tratar la IC en pacientes con DM2. En esta revisión se hace hincapié en los últimos datos publicados al respecto.

Palabras clave:
Insuficiencia cardiaca
Diabetes mellitus tipo 2
Inhibidores SGLT2

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