METABOLIC DISTURBANCES IN DIABETIC CARDIOMYOPATHY

It has been established that diabetes results in a cardiomyopathy, and increasing evidence suggests that an altered substrate supply and uti lization by cardiac myocytes could be the primary injury in the pathog enesis of this specific heart muscle disease. For example, in diabetes , glucose utilization is insignificant, and energy production is shift ed almost exclusively towards beta-oxidation of free fatty acids (FFA) . FFA's are supplied to cardiac cells from two sources: lipolysis of e ndogenous cardiac triglyceride (TG) stores, or from exogenous sources in the blood (as free acid bound to albumin or as TG in lipoproteins). The approximate contribution of FFA from exogenous or endogenous sour ces towards beta-oxidation in the diabetic heart is unknown. In an ins ulin-deficient state, adipose tissue lipolysis is enhanced, resulting in an elevated circulating FFA. In addition, hydrolysis of the augment ed myocardial TG stores could also lead to high tissue FFA. Whatever t he source of FFA, their increased utilization may have deleterious eff ects on myocardial function and includes the abnormally high oxygen re quirement during FFA metabolism, the intracellular accumulation of pot entially toxic intermediates of FFA, a FFA-induced inhibition of gluco se oxidation, and severe morphological changes. Therapies that target these metabolic aberrations in the heart during the early stages of di abetes could potentially delay or impede the progression of more perma nent sequelae that could ensue from otherwise uncontrolled derangement s in cardiac metabolism.