The disease entity "diabetic cardiomyopathy" has been extensively described in young patients with diabetes in the absence of ischemic, hypertensive or valvular heart disease. The most convincing data have been a 30% to 40% incidence of decreased radionuclide angiographic left ventricular ejection fraction response to dynamic exercise. In the current study, the hypothesis was tested that this abnormal ejection fraction response was due to alterations in ventricular loading conditions or cardiac autonomic innervation (extrinsic factors), or both, rather than to abnormalities in intrinsic ventricular systolic fiber function (contractility). Twenty normotensive patients with diabetes (mean age 30 +/- 5 years, mean duration 15 +/- 6 years) and 20 age-matched normal subjects were studied. All patients with diabetes had a normal treadmill exercise tolerance test without evidence of myocardial ischemia. By radionuclide angiography, all normal subjects increased ejection fraction with exercise (62 +/- 4% to 69 +/- 6%; p less than 0.001). In contrast, 11 (55%) of 20 patients with diabetes maintained or increased ejection fraction with exercise (group 1; 62 +/- 4% to 69 +/- 6%; p less than 0.001) and 9 (45%) of 20 showed an exercise-induced decrease (group 2; 73 +/- 4% to 66 +/- 6%; p less than 0.001). No difference in the incidence of microangiopathy, as noted by funduscopic examination, was present between the diabetic groups. Despite the abnormal ejection fraction response to exercise in the group 2 patients with diabetes, all patients with diabetes had a normal response to afterload manipulation, normal baseline ventricular contractility as assessed by load- and heart rate-independent end-systolic indexes and normal contractile reserve as assessed with dobutamine challenge. Autonomic dysfunction did not explain the disparate results between the group 2 patients' radionuclide angiographic data and their load-independent tests of ventricular contractility and reserve. In addition, the high ejection fraction at rest in group 2 patients (73 +/- 4% versus 62 +/- 4% for normal subjects; p less than 0.001) was not related to the abnormal tests of autonomic function. Thus, when left ventricular systolic performance was assessed by load- and rate-independent indexes, there was no evidence for cardiomyopathy in young adult patients with diabetes who have normal blood pressure and no ischemic heart disease.