GLUTAMATE-DECARBOXYLASE AUTOIMMUNITY AND GROWTH-HORMONE SECRETION IN TYPE-I DIABETES-MELLITUS

Insulin-dependent (type I) diabetic patients are known to have an exag gerated growth hormone (GH) response to OH-releasing hormone (GHRH), w hich is hypothesized to be due to a decrease in somatostatin tone. The aim of the study was to ascertain the influence of the presence and a ctivity of the autoimmune process involving a key enzyme (glutamic aci d decarboxylase [GAD]) in the synthetic pathway of a neurotransmitter regulating somatostatin secretion, ie, gamma-aminobutyric acid (GABA), on the GH response to GHRH alone or combined with an acetylcholineste rase inhibitor, pyridostigmine (PD), in patients with type I diabetes mellitus, Twenty non-obese type I diabetic patients and 17 normal subj ects underwent an intravenous (IV) injection of 100 mu g GHRH(1-29)NH2 . Twelve of 20 diabetic subjects and all of the control subjects also underwent a second experimental procedure,administration of 120 mg ora l PD 60 minutes before IV injection of 100 mu g GHRH. Diabetic subject s with serum GAD antibody (GADA) levels more than 3 U (n = 10) showed significantly higher serum GH levels after GHRH injection as compared both with diabetic patients with GADA less than 3 U (n = 10) and with normal controls, whether expressed as absolute or peak values. GH peak s after GHRH were significantly (r(s) = .46, P < .05) correlated with the level of GADA in the whole population of type I diabetic subjects studied. PD significantly enhanced the GH response to GHRH, in terms o f both absolute and peak values, in patients without GADA (n = 6) and in normal subjects. On the contrary, PD failed to enhance the GH respo nse to GHRH in diabetic patients with GADA (n = 6), Our findings sugge st that autoimmunity may play a key role in determining the exaggerate d GH response to GHRH in type I diabetes mellitus, The mechanism under lying this effect is hypothesized to be the production of antibodies t o GAD, a key enzyme in the synthesis of GABA, and in turn a reduced GA BAergic stimulatory tone on somatostatin production at the hypothalami c level. Copyright (C) 1997 by W.B. Saunders Company.