AUTONOMIC FUNCTION AND AUTOANTIBODIES TO AUTONOMIC NERVOUS STRUCTURES, GLUTAMIC-ACID DECARBOXYLASE AND ISLET TYROSINE PHOSPHATASE IN ADOLESCENT PATIENTS WITH IDDM

Recent studies have linked autoimmunity to nervous tissue structures a nd diabetic autonomic neuropathy, but data on the early stage of IDDM and on the natural history of this association are not available. For this reason, we investigated autonomic nervous function, and the prese nce of autoantibodies to sympathetic and parasympathetic nervous struc tures, to glutamic acid decarboxylase (GAD) and tyrosine phosphatase ( IA-2/ICA512) in 85 adolescents with insulin-dependent diabetes mellitu s (IDDM) (mean age 14.7 +/- 1.6 yr, mean duration of diabetes 6.8 +/- 3.5 yr), and 45 age and sex-matched healthy subjects. Nervous tissues autoantibodies were detected using an indirect immunofluorescent compl ement-fixation technique, with monkey adrenal gland, rabbit cervical g anglia and vagus nerve as substrates. GAD and IA-2/ICA512 autoantibodi es were detected by radioimmunoprecipitation assay. Seven patients (8% ) had anti-vagus nerve autoantibodies, 7 other patients (8%) had anti- cervical ganglia autoantibodies, while all controls were negative (P < 0.05). Anti-adrenal medulla antibodies were detected in 16 patients ( 19%) and in 2 control subjects (P < 0.02). None of the patients had au tonomic symptoms. When patients were divided according to the presence or absence of autoantibodies, values of the cardiovascular tests (dee p breathing, 30:15 ratio, Valsalva ratio) were similar in the two grou ps and similar to those in healthy subjects. However, when considered together, patients positive for one or more autoantibody showed a tren d for lower values of deep breathing test and 30:15 ratio test, compar ed with healthy control subjects, which failed to reach conventional s ignificance values(P = 0.17 and P = 0.07, respectively). No correlatio n was found between cardiovascular parameters and metabolic control or diabetes duration. There was no association between autoimmunity to n ervous tissue structures acid presence of GAD and IA-2/ICA512 Ab, and no correlation between these two autoantibodies and values of cardiova scular tests. Our data indicate that autonomic dysfunction is not a ch aracteristic of young diabetic patients, but that autoantibodies again st autonomic nervous structures are present during the first 1 to 15 y r of diabetes. GAD and tyrosine phosphatase appear to be excluded as t arget autoantigens within autonomic structures. Follow-up studies are required to evaluate future autonomic dysfunction and symptoms in thes e patients, and to establish whether the subtle autonomic dysfunction detected and/or the nervous tissue autoantibodies, are predictive of t he development of this complication. (C) 1998 Elsevier Science B.V. Al l rights reserved.