Metabolic abnormalities of cardiomyocytes in diabetes.

There is considerable experimental, pathological, epidemiological, and clinical data to support the entity of "diabetic card iomyopathy". Although its pathogenesis is poorly understood, recent evidence implicates abnormalities in cardiac energy metabolism. Whereas mitochondrial fatty acid oxidation is the chief energy source for the normal postnatal mammalian heart, the relative contribution of glucose utilization pathways is significant, allowing the plasticity necessary for steady ATP production in the context of diverse physiologic and dietary conditions. In the uncontrolled diabetic state, because of the combined effects of insulin resistance and high circulating fatty acids, cardiac myocytes use fatty acids almost exclusively to support ATP synthesis. Studies using diabetic rodent models have shown a direct relationship between the chronic drive on myocardial fatty acid metabolism and the development of cardiomyopathy with ventricular hypertrophy and dysfunction. Fatty acids also play a critical role in triggering cellular insulin resistance through changes in the insulin signalling cascade. There are similarities in cardiac dysfunction in animal models and human type 2 diabetes and/or obesity. For instance, obese young women show increased cardiac fatty acid utilization measured by positron emission tomography and increased myocardial oxygen consumption with reduced cardiac efficiency. Moreover, data indicate that abnormal cardiac energetics occur early in the pathophysiology of type 2 diabetes and are negatively correlated with fasting plasma free fatty acid concentrations.