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      Diabetic Cardiomyopathy: Does the Type of Diabetes Matter?

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          Abstract

          In recent years, type 2 diabetes mellitus has evolved as a rapidly increasing epidemic that parallels the increased prevalence of obesity and which markedly increases the risk of cardiovascular disease across the globe. While ischemic heart disease represents the major cause of death in diabetic subjects, diabetic cardiomyopathy (DC) summarizes adverse effects of diabetes mellitus on the heart that are independent of coronary artery disease (CAD) and hypertension. DC increases the risk of heart failure (HF) and may lead to both heart failure with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF). Numerous molecular mechanisms have been proposed to underlie DC that partially overlap with mechanisms believed to contribute to heart failure. Nevertheless, the existence of DC remains a topic of controversy, although the clinical relevance of DC is increasingly recognized by scientists and clinicians. In addition, relatively little attention has been attributed to the fact that both underlying mechanisms and clinical features of DC may be partially distinct in type 1 versus type 2 diabetes. In the following review, we will discuss clinical and preclinical literature on the existence of human DC in the context of the two different types of diabetes mellitus.

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          Most cited references49

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          Impact of diabetes on cardiac structure and function: the strong heart study.

          Whether diabetes mellitus (DM) adversely affects left ventricular (LV) structure and function independently of increases in body mass index (BMI) and blood pressure is controversial. Echocardiography was used in the Strong Heart Study, a study of cardiovascular disease in American Indians, to compare LV measurements between 1810 participants with DM and 944 with normal glucose tolerance. Participants with DM were older (mean age, 60 versus 59 years), had higher BMI (32.4 versus 28.9 kg/m(2)) and systolic blood pressure (133 versus 124 mm Hg), and were more likely to be female, to be on antihypertensive treatment, and to live in Arizona (all P<0.001). In analyses adjusted for covariates, women and men with DM had higher LV mass and wall thicknesses and lower LV fractional shortening, midwall shortening, and stress-corrected midwall shortening (all P<0.002). Pulse pressure/stroke volume, a measure of arterial stiffness, was higher in participants with DM (P<0.001 independent of confounders). Non-insulin-dependent DM has independent adverse cardiac effects, including increased LV mass and wall thicknesses, reduced LV systolic chamber and myocardial function, and increased arterial stiffness. These findings identify adverse cardiovascular effects of DM, independent of associated increases in BMI and arterial pressure, that may contribute to cardiovascular events in diabetic individuals.
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            Reduced cardiac efficiency and altered substrate metabolism precedes the onset of hyperglycemia and contractile dysfunction in two mouse models of insulin resistance and obesity.

            Hyperglycemia is associated with altered myocardial substrate use, a condition that has been hypothesized to contribute to impaired cardiac performance. The goals of this study were to determine whether changes in cardiac metabolism, gene expression, and function precede or follow the onset of hyperglycemia in two mouse models of obesity, insulin resistance, and diabetes (ob/ob and db/db mice). Ob/ob and db/db mice were studied at 4, 8, and 15 wk of age. Four-week-old mice of both strains were normoglycemic but hyperinsulinemic. Hyperglycemia develops in db/db mice between 4 and 8 wk of age and in ob/ob mice between 8 and 15 wk. In isolated working hearts, rates of glucose oxidation were reduced by 28-37% at 4 wk and declined no further at 15 wk in both strains. Fatty acid oxidation rates and myocardial oxygen consumption were increased in 4-wk-old mice of both strains. Fatty acid oxidation rates progressively increased in db/db mice in parallel with the earlier onset and greater duration of hyperglycemia. In vivo, cardiac catheterization revealed significantly increased left ventricular contractility and relaxation (positive and negative dP/dt) in both strains at 4 wk of age. dP/dt declined over time in db/db mice but remained elevated in ob/ob mice at 15 wk of age. Increased beta-myosin heavy chain isoform expression was present in 4-wk-old mice and persisted in 15-wk-old mice. Increased expression of peroxisomal proliferator-activated receptor-alpha regulated genes was observed only at 15 wk in both strains. These data indicate that altered myocardial substrate use and reduced myocardial efficiency are early abnormalities in the hearts of obese mice and precede the onset of hyperglycemia. Obesity per se does not cause contractile dysfunction in vivo, but loss of the hypercontractile phenotype of obesity and up-regulation of peroxisomal proliferator-activated receptor-alpha regulated genes occur later and are most pronounced in the presence of longstanding hyperglycemia.
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              The Incidence of Congestive Heart Failure in Type 2 Diabetes: An update

              The aims of this study were to update previous estimates of the congestive heart failure (CHF) incidence rate in patients with type 2 diabetes, compare it with an age- and sex-matched nondiabetic group, and describe risk factors for developing CHF in diabetic patients over 6 years of follow-up.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                18 December 2016
                December 2016
                : 17
                : 12
                : 2136
                Affiliations
                Cardiology and Angiology I, University Heart Center Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany; maximilian.hoelscher@ 123456universitaets-herzzentrum.de (M.E.H.); christoph.bode@ 123456universitaets-herzzentrum.de (C.B.)
                Author notes
                [* ]Correspondence: heiko.bugger@ 123456universitaets-herzzentrum.de ; Tel.: +49-761-270-35460; Fax: +49-761-270-34411
                Article
                ijms-17-02136
                10.3390/ijms17122136
                5187936
                27999359
                6fb4d622-61b7-4efd-a972-3e6aa88ab7a0
                © 2016 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 26 October 2016
                : 14 December 2016
                Categories
                Review

                Molecular biology
                diabetic cardiomyopathy,heart,diabetes mellitus
                Molecular biology
                diabetic cardiomyopathy, heart, diabetes mellitus

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