Metabolic alterations in diabetic cardiomyopathy

Abstract

Diabetes mellitus causes cardiomyopathy in diabetic patients and is an important and dominant risk factor for congestive heart failure. With the growing prevalence of diabetes in Canada and throughout the world, diabetic cardiomyopathy is a signifi cant public health issue. Diabetic cardiomyopathy has been defi ned as myocardial dysfunction that occurs in a diabetic milieu independent of identifi ed causes such as coronary atherosclerosis, hypertension, or valvular heart disease. Alterations in ventricular structure as well as left ventricular systolic and diastolic dysfunctions have been reported in diabetic patients despite well-controlled glycemic levels and disease free coronary vasculature. Metabolic abnormalities such as hyperlipidemia, hyperinsulinemia, and hyperglycemia predispose the heart to cellular, structural, and functional alterations that manifest as the cardiac phenotype observed in this diabetic population. These mechanisms are likely to act synergistically and are believed to potentiate one another. Hyperglycemia is an essential factor in the development of cardiomyopathy and exerts its effects by altering protein kinase C, increasing oxidative stress and causing abnormalities in lipid metabolism and calcium ion homeostasis. Regardless of the extensive information available on diabetic cardiomyopathy, translational research is scarce due to the lack of clinical trials, and therefore, much of our current knowledge is extrapolated from animal models. This review focuses on illustrating the various metabolic alterations that contribute to the development and progression of diabetic cardiomyopathy.