Patients with type 2 diabetes mellitus (T2DM) have a 2-fold to 4-fold greater risk of cardiovascular mortality than nondiabetic individuals. The overall mortality rate of patients with T2DM is approximately twice that of people without diabetes. The excess in-hospital mortality of these patients is primarily due to an increased risk of congestive heart failure. Reduced compensatory ability of the noninfarcted myocardium and an underlying abnormality in the myocardial substrate metabolism (referable to the diabetic state) may also contribute to poor outcomes. Insulin resistance (IR) is a significant predictor of cardiovascular mortality and morbidity across a spectrum of glucose tolerance. Cardiac mass increases across the range of IR in subjects without diabetes, as well as across the range of glucose intolerance in subjects with diabetes. In one study, elevated fasting plasma glucose was an independent predictor of hospitalization for heart failure. Optimization of cardiac metabolism could become a new target for therapeutic intervention in patients with ischemic heart disease and diabetes.