Diabetic cardiomyopathy: prevalence, determinants and potential treatments

Abstract

The prevalence of type 2 diabetes (T2D) has reached a pandemic scale. These patients are at a substantially elevated risk of developing cardiovascular disease, with heart failure (HF) being a leading cause of morbidity and mortality. Even in the absence of traditional risk factors, diabetes still confers up to a twofold increased risk of developing HF. This has led to identifying diabetes as an independent risk factor for HF and recognition of the distinct clinical entity, diabetic cardiomyopathy. Despite a wealth of research interest, the prevalence and determinants of diabetic cardiomyopathy remain uncertain. This limited understanding of the pathophysiology of diabetic heart disease has also hindered development of effective treatments. Tight blood-glucose and blood-pressure control have not convincingly been shown to reduce macrovascular outcomes in T2D. There is, however, emerging evidence that T2D is reversible and that the metabolic abnormalities can be reversed with weight loss. Increased aerobic exercise capacity is associated with significantly lower cardiovascular and overall mortality in diabetes. Whether such lifestyle modifications as weight loss and exercise may ameliorate the structural and functional derangements of the diabetic heart has yet to be established. In this review, the link between T2D and myocardial dysfunction is explored. Insights into the structural and functional perturbations that typify the diabetic heart are first described. This is followed by an examination of the pathophysiological mechanisms that contribute to the development of cardiovascular disease in T2D. Lastly, the current and emerging therapeutic strategies to prevent or ameliorate cardiac dysfunction in T2D are evaluated.

Keywords: cardiometabolic disease; diabetic cardiomyopathy; heart failure; type 2 diabetes.

Figure 1.

Local and systemic perturbations involved in the pathophysiology of diabetic cardiomyopathy. RAAS, renin–angiotensin–aldosterone system; CAD, coronary artery disease; LV, left ventricle.

Figure 2.

Myocyte energy metabolism and alterations that contribute to lipotoxicity and glucotoxicity. CoA, coenzyme A; CD36, cluster of differentiation 36; FACS, ; FFAs, free fatty acids; CPT, carnitine palmitoyltransferase; FADH₂, flavine adenine dinucleotide; GLUT 4, glucose transporter type 4; MPC, mitochondrial pyruvate carrier; NADH, nicotinamide adenine dinucleotide; TCA, tricarboxylic acid; ETC, electron-transport chain; ATP, adenosine triphosphate.