INTRODUCTION AND OBJECTIVES The natural history of diabetic cardiomyopathy remains unclear, mainly due to concurrent coronary disease or hypertension. Since the presence of confounding factors is less likely in youngsters, they constitute a suitable study model to analyze early stages of diabetic cardiomyopathy. PATIENTS AND METHODS We screened 33 young normotensive asymptomatic patients with type I diabetes mellitus. Mean age was 28 +/- 8 y (range 18 to 46 y) and there were 14 men. RESULTS 2-D Echo showed normal left ventricular size and wall motion in all patients but one. Radionuclide basal ejection fraction was 56.5 +/- 6.6% and increased to 63 +/- 7.4% (p < 0.02) on exercise. According to Rozansky criteria, 16 patients had an abnormal response. Abnormal stress sestamibi was detected in 18 patients and only 3 had reversible defects. Coronary angiography was performed in 11 patients with at least one abnormal non-invasive study response. Coronary angiography revealed normal vessels in all patients and left anterior descending blood flow velocity (Doppler) increased 4 fold after papaverine infusion. Left ventricular biopsies showed hypertrophy (either nuclear or cellular) in 11, myocytolysis in 6, interstitial fibrosis in 9 and lipid deposits in 4. Morphometric analysis of cardiac samples comparing the diabetic group and a control group showed that the volume fraction of fibrosis (0.19 +/- 0.06 vs 0.10 +/- 0.06; p < 0.01), fiber area -mu2- (1,062 +/- 547 vs 600 +/- 167; p < 0.02) and fiber diameter -mu- (24.2 +/- 3.3 vs 15.1 +/- 3.4; p < 0.001) were higher in the former; and volume fraction of the myocytes was higher in the latter (0.71 +/- 0.006 vs 0.89 +/- 0.07; p < 0.001). CONCLUSIONS Left ventricular dysfunction, not related to coronary atherosclerosis or small vessel disease, is frequent in asymptomatic young diabetic patients. Abnormal pathologic findings are common in the type of cell hypertrophy, interstitial fibrosis, myocytolysis and lipid deposits.