The Pathophysiological Basis of Diabetic Cardiomyopathy Development

Diabetes mellitus (DM) provokes widely known structural and functional dyscoordination of the myocardium performance. A cascade of pathophysiological changes occurs 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 by forming ceramides, diacylglycerol, and reactive oxygen species (ROS). Hyperglycemia also causes an increase in the content of reactive oxygen species and the formation of advanced glycation end (AGE) products, which is accompanied by the development of cardiac glucotoxicity. The combination of these pathophysiological processes, ATP deficiency, and the development of myocardial fatty degeneration induce calcium stress, as well as dysfunction of mitochondria and endoplasmic reticulum, activation of signaling pathways of protein kinase C (PKC), mitogen-activated protein kinases (MAPK), etc., causing chronic sluggish inflammation, as well as first diastolic and further systolic dysfunction, and myocardial fibrosis. This article reviews the data on diabetic alteration of the cardiovascular system.