Following a myocardial infarction diabetic patients have almost twice the rate of mortality and 3 times the rate of progression to congestive heart failure when compared to wx nondiabetic patients 1. These observations suggest that defects specific to the diabetic myocardium contribute to wx the greater mortality in diabetic patients 1, 2. Abnormalities in myocardial energy metabolism in the diabetic population are probably an important contributing factor to this greater mortality. Normal cardiac function is dependent on a constant rate of resynthesis of ATP by mitochondrial oxidative phosphorylation and, to a much lesser extent, glycolysis. Oxidation of fatty acids is normally responsible wx for about 60–90% of the ATP resynthesized 3–7, with the balance coming from the oxidation of pyruvate derived Ž. from glycolysis and lactate uptake Fig. 1. Even in the absence of diabetes myocardial ischemia results in profound derangements in myocardial substrate utilization, particularly impaired pyruvate oxidation and increased lacwx tate production 3–7. This is particularly evident during reperfusion of ischemic myocardium, where rapid normalization in the rate of oxygen consumption occurs, but pyruvate oxidation is impaired, and rates of fatty acid oxidation are disproportionately high, all of which correw x sponds with a decrease in contractile work 8–15. Diabetic patients, even in the absence of ischemia, have decreased myocardial glucose and lactate uptake, and a greater use of free fatty acids and ketone bodies relative to the nondiabetic population. Hearts from animals with ex-