Autoantibodies against adrenal medulla in type 1 and type 2 diabetes mellitus: No evidence for an association with autonomic neuropathy

Objective. To examine the role of autoimmunity in the development of autonomic neuropathy in diabetes mellitus. Design. Retrospective cross-sectional study. Setting. The Department of Medicine, University Hospital, Uppsala, and the Department of Endocrinology, University of Lund, Malmo General Hospital, Malmo, Sweden. Subjects and main outcome measures. We examined 135 patients with type 1 (n = 96) or type 2 (n = 39) diabetes mellitus, Tests for cardiovascular autonomic functions were performed, and patient sera were analysed for the presence of autoantibodies against the adrenal medulla by indirect immunofluorescence, Western blot and immunoprecipitation techniques. Results. Sera from 13% (12/96) of the type 1 and 20% (8/39) of the type 2 patients showed a positive cytoplasmic immunofluorescence (IF) staining of the adrenal medullary cells, as did 20% (30/151) of sera from healthy controls. Fifty-eight and 64% of type 1 and type 2 patients, respectively, had cardiovascular autonomic neuropathy, but no correlation between autonomic neuropathy and positive IF against the adrenal medulla was observed, with the exception of significant drops in diastolic blood pressure 8 min after tilt (P < 0.005) in type 1 patients, The various IF-positive sera reacted with several different proteins when analysed with Western blot technique using a total homogenate of the bovine adrenal medulla, These did not correspond to any of the proteins involved in the synthesis or storage of catecholamines which were considered as putative autoantigens. Conclusion. The finding of similar frequencies of immunoglobulins binding to adrenal medulla in both type 1 and 2 diabetic patients as well as in normal controls, argues against a role of anti-adrenomedullary antibodies in the pathogenesis of autonomic diabetic neuropathy.