Myocardial Dysfunction and Adrenergic Cardiac Innervation in Patients With Insulin-Dependent Diabetes Mellitus

Background. Insulin-dependent diabetes mellitus (IDDM) is associated with an increased incidence of heart failure due to several factors, and in some cases specific cardiomyopathy has been suggested. Objectives. This study sought to assess the mechanisms of exercise-induced left ventricular (LV) dysfunction in asymptomatic patients with IDDM in the absence of hypertensive or coronary artery disease. Methods. Fourteen consecutive patients with IDDM were enrolled (10 men, 4 women; mean [±SD] age 28.5 ± 6 years); 10 healthy subjects matched for gender (7 men, 3 women) and age (28.5 ± 3 years) constituted the control group. LV volume, LV ejection fraction (LVEF) and end-systolic wall stress were calculated by two-dimensional echocardiography at rest and during isometric exercise. LV contractile reserve was assessed by post-extrasystolic potentiation (PESP) obtained by transesophageal cardiac electrical stimulation and dobutamine infusion. Myocardial iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy was performed to assess adrenergic cardiac innervation. Results. Diabetic patients were classified into group (n = 7), with an abnormal LVEF response to handgrip (42 ± 7%), and group B (n = 7), with normal response (72 ± 8%). Baseline LVEF was normal in both group and B patients (60 ± 6% vs. 61 ± 7%, p = NS). In group patients, the LV circumferential wall stress–LVEF relation showed an impairment in LVEF disproportionate to the level of LV afterload. No significant changes in LVEF occurred during dobutamine (60 ± 6% vs. 64 ± 10%, p = NS), whereas PESP significantly increased LVEF (60 ± 6% vs. 74 ± 6%, p < 0.001); PESP at peak handgrip normalized the abnormal LVEF (42 ± 7% vs. 72 ± 5%, p < 0.001); and MIBG uptake normalized for body weight or for LV mass was lower than that in normal subjects (1.69 ± 0.30 vs. 2.98 ± 0.82 cpm/MBq per g, p = 0.01) and group B diabetic patients (vs. 2.79 ± 0.94 cpm/MBq per g, p = 0.01). Finally, strong linear correlation between LVEF at peak handgrip and myocardial MIBG uptake normalized for LV mass was demonstrated in the study patients. Conclusions. Despite normal contractile reserve, defective blunted recruitment of myocardial contractility plays an important role in determining exercise LV dysfunction in the early phase of diabetic cardiomyopathy. This abnormal response to exercise is strongly related to an impairment of cardiac sympathetic innervation.