Diabetic cardiomyopathy: epidemiology, etiology and pathogenesis

Abstract

This paper presents detailed analysis of current views on the epidemiology, etiology and pathogenesis of diabetic cardiomyopathy. Diabetes mellitus causes various structural and functional modifications of myocardial tissue. These pathophysiological changes occur due to metabolic disorders caused by hyperglycemia, insulin resistance and dyslipidemia. Free fatty acids can stimulate oxidation and accumulate in the cytosol, leading to lipotoxic effects through the formation of ceramides, diacylglycerol and reactive oxygen species. Hyperglycemia also causes an increase in reactive oxygen species and the formation of end products of glycation, which is accompanied by the development of cardiac glucose toxicity. The combination of these pathophysiological processes, adenosine triphosphate deficiency and lipo-/glucose toxicity are promoters of Ca2+ imbalance, mitochondrial/endoplasmic reticulum stress and apoptosis, activation of protein kinase C signaling pathways, mitogen-activated protein kinases, ubiquitin-proteasome system, proteotoxic stress, activation of the cyclic modulator of adenosine 5’-monophosphates, renin-angiotensin system, causing low-grade chronic inflammation, development of diastolic and, subsequently, systolic dysfunction, myocardial fibrosis. Chronic hyperglycemia, insulin resistance and hyperinsulinemia cause cardiomyocyte resistance to insulin and metabolic disorders that exacerbate mitochondrial dysfunction, oxidative stress, production of glycation end products, alteration of Ca2+ metabolism in the mitochondria, chronic low-grade inflammation, activation of the renin-angiotensin-aldosterone system, stress of the endoplasmic reticulum, death of cardiomyocytes, as well as microvascular dysfunction. These pathophysiological disorders contribute to cardiac stiffness, hypertrophy and fibrosis, the development of diastolic and systolic myocardial dysfunction and heart failure.

Keywords

• diabetes mellitus
• diabetic cardiomyopathy
• epidemio­logy
• etiology
• pathogenesis
• review