Fig. 1.

Pathophysiological mechanisms of diabetic cardiomyopathy. Hyperglycemia, insulin resistance, and hyperinsulinemia induce cardiac insulin resistance and metabolic disorders that increase mitochondria dysfunction, oxidative stress, AGEs, impairment of mitochondria Ca²⁺ handling, inflammation, activation of RAAS, autonomic neuropathy, endoplasmic reticulum stress, cardiomyocyte death, as well as microvascular dysfunction. These pathophysiological abnormalities promote cardiac stiffness, hypertrophy, and fibrosis, resulting in cardiac diastolic dysfunction, systolic dysfunction, and heart failure. Abbreviations: AGEs, advanced glycation end-products; RAAS, renin-angiotensin-aldosterone system.