Evidence for specific autoimmunity against sympathetic and parasympathetic nervous tissues in Type 1 diabetes mellitus and the relation to cardiac autonomic dysfunction

Diabet Med. 1998 Jun;15(6):467-72. doi: 10.1002/(SICI)1096-9136(199806)15:6<467::AID-DIA621>3.0.CO;2-Q.

Abstract

There is growing evidence for the involvement of immunological factors in the pathogenesis of cardiac autonomic dysfunction in Type 1 diabetes mellitus (DM). To evaluate the presence of autoantibodies against autonomic nervous tissues and their relationship with tests of autonomic function, 64 newly diagnosed and 142 long duration Type 1 DM patients were investigated for sympathetic and parasympathetic ganglia (CF-SG and CF-PSG) autoantibodies with a complement-fixing indirect immunofluorescence technique. Five cardiac reflex tests were performed to assess autonomic function. Fifty-seven patients with neurological diseases other than diabetic neuropathy and 131 healthy control subjects were also tested for CF-SG and CF-PSG autoantibodies. CF-SG autoantibodies were observed in 47 (23%) and CF-PSG autoantibodies in 21 (10%) of 206 Type 1 DM patients (p < 0.001). In contrast, these autoantibodies were detected in 3 (5%) and 1 (2%) of patients with non-diabetic neurological diseases and 3 (2%) and 4 (3%) of control subjects (p < 0.01, p < 0.05, p < 0.0001, p < 0.05 vs Type 1 DM patients). All except two Type 1 DM patients with CF-PSG autoantibodies also presented with CF-SG autoantibodies. In diabetic patients with long duration, CF-SG autoantibodies were more frequent in patients with ECG-based cardiac autonomic neuropathy (CAN; > or =2 of 5 cardiac reflex tests abnormal) compared to patients without CAN although this did not reach statistical significance (29% vs 17%, p = 0.06). However, 4 (80%) of 5 newly diagnosed and 23 (32%) of 73 established Type 1 DM patients with abnormalities in heart rate variation during deep breathing and/or standing from lying presented with CF-SG autoantibodies compared to 12 (25%) of 58 newly diagnosed (p < 0.05) and 7 (11%) of 63 established Type 1 DM patients (p < 0.01), in whom both tests were normal. The results suggest that autoimmune factors contribute to the pathogenesis of cardiac autonomic dysfunction in Type 1 DM and that autoantibodies against sympathetic and parasympathetic nervous tissues are relatively specific for Type 1 DM.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Antibody Specificity
  • Autoimmunity*
  • Autonomic Nervous System Diseases / immunology*
  • Case-Control Studies
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetic Neuropathies / immunology*
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Ganglia, Autonomic / immunology
  • Ganglia, Parasympathetic / immunology*
  • Heart / innervation
  • Humans
  • Male
  • Middle Aged
  • Sympathetic Nervous System / immunology*