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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/cdn\/css\/http\/css_Xg7z6oCTVgud_Q0huYz9x9iiD5H_2YPSJ5z2ZViSWdY.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EIt is currently estimated that 5.1 million adults in the United States have heart failure (HF). By the year 2030, this number is expected to increase by 25%. Over the last several decades, there has also been a marked increase in the prevalence of diabetes [Centers for Disease Control and Prevention. Available at \u003Ca href=\u0022http:\/\/www.cdc.gov\/diabetes\/statistics\u0022\u003Ehttp:\/\/www.cdc.gov\/diabetes\/statistics\u003C\/a\u003E]. This article discusses the relationship between and coexistence of these two diseases including whether the presence of diabetes should influence the management of patients with HF, and diabetic cardiac dysfunction\u2014lipotoxic cardiomyopathy.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EHeart Failure\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes \u0026amp; Endocrinology Clinical Trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EHeart Failure\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes \u0026amp; Endocrinology Clinical Trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ECardiology\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EIt is currently estimated that 5.1 million adults in the United States have heart failure (HF). By the year 2030, this number is expected to increase by 25%. Over the last several decades, there has also been a marked increase in the prevalence of diabetes [Centers for Disease Control and Prevention. Available at \u003Ca href=\u0022http:\/\/www.cdc.gov\/diabetes\/statistics\u0022\u003Ehttp:\/\/www.cdc.gov\/diabetes\/statistics\u003C\/a\u003E]. David Aguilar, MD, Baylor College of Medicine, Houston, Texas, USA, discussed the relationship between and coexistence of these two diseases.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EDiabetes has long been known to amplify the risk for all forms of cardiovascular disease (CVD) and when it develops in patients with HF, it is associated with increased mortality (\u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E) [Cubbon RM et al. \u003Cem\u003EDiab Vasc Dis Res\u003C\/em\u003E 2013; Martinez-Selles M et al. \u003Cem\u003EEur J Heart Fail\u003C\/em\u003E 2012; MacDonald MR et al. \u003Cem\u003EEur Heart J\u003C\/em\u003E 2008; From AM et al. \u003Cem\u003EAm J Med\u003C\/em\u003E 2006].\u003C\/p\u003E\u003Cdiv id=\u0022T1\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/13366\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/13366\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/13366\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-4\u0022 class=\u0022first-child\u0022\u003EIncreased Mortality in Patients With HF and Diabetes Mellitus\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-6\u0022\u003EThe increased mortality is even more striking among older individuals (aged \u226565 years) with diabetes who go on to develop HF, with such patients having a mortality rate of 32.7\/100 person-years compared with similarly aged diabetes patients without HF who have a mortality rate of 3.7\/100 person-years (HR, 10.6; 95% CI, 10.4 to 10.9) [Bertoni AG et al. \u003Cem\u003EDiabetes Care\u003C\/em\u003E 2004]. The coexistence of diabetes and HF is also associated with an increased the rate of HF hospitalizations [Shah AM et al. \u003Cem\u003EEur J Heart Fail\u003C\/em\u003E 2010; MacDonald MR et al. \u003Cem\u003EEur Heart J\u003C\/em\u003E 2008; Murcia AM et al. \u003Cem\u003EArch Intern Med\u003C\/em\u003E 2004]. Future studies are needed to better understand the complex interaction of these 2 diseases and to develop treatment strategies to lower the health burden of HF and diabetes, noted Dr. Aguilar.\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EMary N. Walsh, MD, St. Vincent Heart Center, Indianapolis, Indiana, USA, discussed whether the presence of diabetes should influence the management of patients with HF. Dr. Walsh reinforced diabetes as a driver of HF adding that this is particularly true for women [Levy D et al. \u003Cem\u003EJAMA\u003C\/em\u003E 1996], even among those with no other risk factors and especially when the diabetes is uncontrolled [Bibbins-Domingo K et al. \u003Cem\u003ECirculation\u003C\/em\u003E 2004]. She then asked \u201cAre diabetic patients HF patients?\u201d The answer is \u201cYes\u201d according to the 2001 American College of Cardiology Foundation (ACCF)\/American Heart Association (AHA) guidelines for the evaluation and management of chronic HF in adults [Hunt SA et al. \u003Cem\u003EJ Am Coll Cardiol\u003C\/em\u003E 2001] in which Stage A HF includes patients with diabetes.\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EWhether and how diabetes influences short- and long-term outcomes among patients with HF appears to be related to multiple factors including time, age, and sex. In one study of \u0026gt;116,000 patients (13% with diabetes), diabetes was a significant independent predictor of mortality at 1 year. The longer term risk was greatest in younger patients, particularly women. Diabetes was also a significant independent predictor of readmission for HF, and again, the risk was greatest in younger women [MacDonald M et al. \u003Cem\u003ECirc Heart Fail\u003C\/em\u003E 2008].\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003EThe 2013 ACCF\/AHA guideline for the management of HF provides some guidance for how to treat patients with diabetes and HF [Yancy CW et al. \u003Cem\u003EJ Am Coll Cardiol\u003C\/em\u003E 2013]. Among patients with Stage A HF, the 2013 guidelines recommend that clinicians make every effort to control hyperglycemia (Class I, Level of Evidence [LoE] C), even though control has not yet been shown to reduce the subsequent risk of HF. The reason for this is that many of the standard diabetes therapies can prevent the development of other HF risk factors and may by themselves directly lower the likelihood of HF. The guidelines recommend angiotensin-converting-enzyme (ACE) inhibitors (or angiotensin II receptor blockers [ARBs] in patients intolerant of ACE inhibitors) for all patients (regardless of diabetes status) with Stage C HF with reduced ejection fraction (HFrEF) and current or prior symptoms (both Class I, LoE A). With respect to \u03b2-blockers, the current guidelines recommend the use of bisoprolol, carvedilol, or sustained-release metoprolol succinate for all patients with current or prior symptoms of HFrEF (Class I, LoE A). In HF patients with diabetes, the marked clinical benefits of these therapies are considered to outweigh the risks of hypoglycemia and dyslipidemia or decreased insulin sensitivity. Clear benefit has also been shown for aldosterone receptor antagonists in HF patients with a history of diabetes (Class I, LoE B). Patients with diabetes, left ventricular dysfunction, mildly symptomatic HF, and wide QRS complex derive similar benefit from cardiac resynchronization therapy defibrillation compared with patients without diabetes [Martin D et al. \u003Cem\u003ECirc Heart Fail\u003C\/em\u003E 2011], and those without significant diabetic complications are eligible for transplantation [Russo M et al. \u003Cem\u003ECirculation\u003C\/em\u003E 2006]. There are no differences in the recommendations for patients with diabetes and HF with preserved ejection fraction.\u003C\/p\u003E\u003Cp id=\u0022p-10\u0022\u003EDaniel Kelly, MD, Sanford-Burnham Medical Research Institute at Lake Nona, Orlando, Florida, USA, discussed an emerging theory in diabetic cardiac dysfunction-lipotoxic cardiomyopathy, which he believes reflects a more systemic problem driven by caloric excess.\u003C\/p\u003E\u003Cp id=\u0022p-11\u0022\u003EFor centuries, pathologists have noted an accumulation of neutral lipids in cardiac myocytes during autopsy of morbidly obese individuals, many of whom had diabetes. More recently imaging studies in living patients with obesity and diabetes have shown evidence of increased myocardial fatty acid utilization and cardiac steatosis [Herrero P et al. \u003Cem\u003EJ Am Coll Cardiol\u003C\/em\u003E 2006; Szczepaniak LS et al. \u003Cem\u003EMagn Reson Med\u003C\/em\u003E 2003]. These results, along with other studies focused on glucose toxicity and microvascular disease have led to a general view of the metabolic disturbances that occur in diabetic cardiac dysfunction. This view begins with insulin resistance in type 2 diabetes that reduces the ability of the heart to use glucose as fuel and consequently forces increased fatty acid burning, which in turn results in lipid accumulation that is associated with early-stage diastolic and then systolic ventricular dysfunction, and sensitivity to ischemic insult. The rationale for serum lipid-lowering strategies in the treatment of diabetic cardiomyopathy has been demonstrated in several preclinical mouse models [Duncan JG et al. \u003Cem\u003ECirculation\u003C\/em\u003E 2010; Yang J et al. \u003Cem\u003ECirc Res\u003C\/em\u003E 2007; Finck BN et al. \u003Cem\u003EProc Natl Acad Sci USA\u003C\/em\u003E 2003].\u003C\/p\u003E\u003Cp id=\u0022p-12\u0022\u003EDr. Kelly presented a model for lipotoxic organ dysfunction (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E) in which the adipocytes have no more capacity to store fat and the calories end up in other tissues as neutral lipid droplets\u2014including the heart. To define the mechanism and perhaps identify targets for metabolic modulator therapy that would be given along with traditional HF therapy, Dr. Kelly and colleagues have embarked on a small-molecule high throughput screen. One promising compound has been shown to reduce myocyte triglyceride accumulation and increases fat burning capacity, fatty acid oxidation rates, and glucose uptake. Further studies are needed to determine if this compound has the potential improve clinical outcomes in patients with diabetes and warrents further study.\u003C\/p\u003E\u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/20\/35\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Systemic Model of Lipotoxic Organ Dysfunction\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-752587403\u0022 data-figure-caption=\u0022Systemic Model of Lipotoxic Organ Dysfunction\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/20\/35\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/20\/35\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/20\/35\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/13365\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-13\u0022 class=\u0022first-child\u0022\u003ESystemic Model of Lipotoxic Organ Dysfunction\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EReproduced with permission from D Kelly, MD.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-14\u0022\u003EAlthough the exact mechanism remains unclear there is little doubt that there is a relationship between diabetes and HF and that the incidence of both of these life altering diseases is increasing. Patients with diabetes should be encouraged manage their risk through lifestyle changes and adherence to their treatment regimen. Clinicians treating patients with HF should manage their patients according to published guidelines.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2013 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/13\/20\/35.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nznju2\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nznju2\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_tables.js?nznju2\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}