Heart disease is the leading cause of death in patients with type 2 diabetes, and type 2 diabetic patients show increased risk for developing heart failure and increased mortality rate following acute myocardial infarction. Cardiac complications in type 2 diabetes are due to coronary heart disease, but also to the development of a specific diabetic cardiomyopathy (i.e. ventricular dysfunction in the absence of coronary heart disease or hypertension). The diabetic heart is associated with altered calcium handling, increased oxidative stress and fibrosis, as well as altered cardiac metabolism (increased fatty acid oxidation and impaired glucose utilization) and increased myocardial oxygen consumption (MVO2). Although the pathogenesis of diabetic cardiomyopathy is multifactorial and complex, several transgenic mouse models have supported the notion that altered cardiac metabolism may play an important role. The type 2 diabetic db/db mouse, a monogenic model of obesity due to a mutation in the leptin gene (Leprdb), has contributed to elucidating the role of altered myocardial substrate utilization and cardiac efficiency (the relationship between MVO2 and cardiac function) in the development of diabetic cardiomyopathy and increased susceptibility to ischemic injury.