Myocardial glucotoxicity and lipotoxicity in uncontrolled diabetes mellitus

Myocardial glucotoxicity and lipotoxicity in uncontrolled diabetes mellitus

Metabolism of cardiac myocytes is abnormal in diabetes mellitus. There is decreased myocardial consumption of glucose and lactate. Use of free fatty acids is increased as the inability to metabolize pyruvate inhibits glycolysis. Inhibition of glycolysis leads to a decrease in ATP production and impaired relaxation. Chronic hyperglycemia produces advanced glycation end products and reactive oxygen species. Irreversible cross-linkages of collagen with advanced glycation end products is one of the possible mechanisms responsible for diabetic cardiomyopathy. These together have been called myocardial glucotoxicity. Increased free fatty acid turnover causes increased myocardial oxygen consumption and accumulation of intermediates contributing to myocardial lipotoxicity. Glucotoxicity and lipotoxicity are the forerunners of myocardial contractile dysfunction.