ular hypertrophy and increased heart mass, with mildly reduced left ventricular systolic performance. 22 On the microscopic level, histological studies of autopsy and biopsy specimens demonstrate that diabetic humans and animals made diabetic share a constellation of cardiac morphological abnormalities, including myocyte hypertrophy, perivascular fibrosis, and increased quantities of matrix collagen, cellular triglyceride, and cell membrane lipid. All of these findings are consistent with the nonenzymatic glycation of vascular and membrane proteins, increased cellular fatty acid uptake, and hyperglycemia-induced oxidative stress, which are characteristic of the diabetes state. 23, 24 These morphological changes, especially when considered together with the changes in myocardial calcium metabolism and contractile protein composition observed in experimental diabetes, would be predicted to confer clinically significant impairment in diastolic compliance. Doppler echocardiographic studies have revealed that qualitatively similar patterns of diastolic dysfunction are an early feature of diabetes in both animal models25 and humans. 26, 27 In patients with diabetes, the reduction of diastolic compliance is associated with characteristically abnormal myocardial acoustic properties and correlates positively with the severity and duration of diabetes and negatively with the ability to perform treadmill exercise. 28 The relevance of this type of diastolic dysfunction to diabetes per se is clouded by the frequent coexistence of hypertension with diabetes; however, the recognition that impaired left ventricular diastolic filling can be demonstrated very early in the course of monogenetic type-2 diabetes in animal models, before the onset of hypertension, vasculopathy, or even fasting hyperglycemia, suggests diastolic dysfunction is an effect of diabetes itself. 25 An association of diabetes with myocardial diastolic dysfunction and poor exercise performance is undisputed. There is less evidence that diabetes itself can cause left ventricular dilatation and failure in the absence of coronary artery disease or hypertension. Nevertheless, because of the coexistence of diabetes, hypertension, and coronary artery disease, these factors may act synergistically to produce heart failure on the basis of left ventricular systolic dysfunction. For this reason, it is difficult to target a diabetes-specific metabolic, functional, or structural abnormality for pharmacological treatment of heart failure in diabetes. Furthermore, it still remains to be seen whether the degree of metabolic control affects the function of the heart in diabetes. The focus therefore shifts once more to the identification and treatment of comorbidities in diabetes.