Autoantibodies against sympathetic ganglia and evidence of cardiac sympathetic dysinnervation in newly diagnosed and long-term IDDM patients

To investigate the presence of autoantibodies against sympathetic nervous tissue and their correlation with cardiac sympathetic dysinnervation in insulin-dependent diabetes mellitus (IDDM), 20 newly diagnosed (age 26±6 years) and 48 long-term IDDM patients (age 40±13 years, duration of diabetes 22±12 years) without myocardial perfusion abnormalities (normal 99mTC-methoxyisobutylisonitrile uptake) were assessed for myocardial 123I-metaiodobenzylguanidine (123I-MIBG) uptake and complement-fixing sympathetic ganglia (CF-SG) autoantibodies. Both groups of patients were also studied for islet cell antibodies (ICA) and ECG-based cardiac autonomic neuropathy. Eighty control subjects (age 18–49 years) were investigated for CF-SG autoantibodies. Eight newly diagnosed (40%) and 12 long-term (25%) IDDM patients exhibited CF-SG autoantibodies, compared to 4 control subjects (5%; p<0.01, p<0.05). In long-term diabetic patients, the reduction of global but not of regional myocardial 123I-MIBG uptake correlated with CF-SG autoantibodies (r=0.34, p=0.02). Newly diagnosed diabetic patients did not show an association between CF-SG autoantibodies and global or regional myocardial 123I-MIBG uptake. ECG-based cardiac autonomic neuropathy (≥ two of five cardiac reflex tests abnormal) was present in 22 and absent in 26 long-term IDDM patients, of whom 9 (41%) and 3 (12%), respectively were positive for CF-SG autoantibodies (p=0.02). Only 1 newly diagnosed IDDM patient demonstrated ECG-based cardiac autonomic neuropathy and was also positive for CF-SG autoantibodies. Although they are somewhat suggestive, results concerning autoantibodies against sympathetic nervous tissue and cardiac sympathetic dysinnervation do not strongly support the view that autoimmune mechanisms play a major role in the pathogenesis of cardiac sympathetic neuropathy in IDDM.