Glutamate decarboxylase autoimmunity and growth hormone secretion in type I diabetes mellitus

Giustina, Andrea; Desenzani, Paolo; Perini, Paola; Bazzigaluppi, Elena; Bodini, Corrado; Bossoni, Simonetta; Poiesi, Claudio; Wehrenberg, William B.; Bosi, Emanuele

« Previous Next »Metabolism - Clinical and Experimental
Volume 46, Issue 4 , Pages 382-387, April 1997

Glutamate decarboxylase autoimmunity and growth hormone secretion in type I diabetes mellitus☆

Andrea Giustina
- Address reprint requests to Andrea Giustina, MD, Clinica Medica c/o 2 Medicina, Spedali Civili, 25125 Brescia, Italy.
- Endocrine Section, Department of Internal Medicine and Chemistry, University of Brescia, Brescia, Italy
- Department of Medicine, San Raffaele Hospital, University of Milano, Milano, Italy
- Department of Health Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI, USA
Paolo Desenzani
- Endocrine Section, Department of Internal Medicine and Chemistry, University of Brescia, Brescia, Italy
- Department of Medicine, San Raffaele Hospital, University of Milano, Milano, Italy
- Department of Health Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI, USA
Paola Perini
- Endocrine Section, Department of Internal Medicine and Chemistry, University of Brescia, Brescia, Italy
- Department of Medicine, San Raffaele Hospital, University of Milano, Milano, Italy
- Department of Health Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI, USA
Elena Bazzigaluppi
- Endocrine Section, Department of Internal Medicine and Chemistry, University of Brescia, Brescia, Italy
- Department of Medicine, San Raffaele Hospital, University of Milano, Milano, Italy
- Department of Health Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI, USA
Corrado Bodini
- Endocrine Section, Department of Internal Medicine and Chemistry, University of Brescia, Brescia, Italy
- Department of Medicine, San Raffaele Hospital, University of Milano, Milano, Italy
- Department of Health Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI, USA
Simonetta Bossoni
- Endocrine Section, Department of Internal Medicine and Chemistry, University of Brescia, Brescia, Italy
- Department of Medicine, San Raffaele Hospital, University of Milano, Milano, Italy
- Department of Health Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI, USA
Claudio Poiesi
- Endocrine Section, Department of Internal Medicine and Chemistry, University of Brescia, Brescia, Italy
- Department of Medicine, San Raffaele Hospital, University of Milano, Milano, Italy
- Department of Health Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI, USA
William B. Wehrenberg
- Endocrine Section, Department of Internal Medicine and Chemistry, University of Brescia, Brescia, Italy
- Department of Medicine, San Raffaele Hospital, University of Milano, Milano, Italy
- Department of Health Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI, USA
Emanuele Bosi
- Endocrine Section, Department of Internal Medicine and Chemistry, University of Brescia, Brescia, Italy
- Department of Medicine, San Raffaele Hospital, University of Milano, Milano, Italy
- Department of Health Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI, USA

Received 17 June 1996; accepted 1 October 1996.

Abstract

Insulin-dependent (type I) diabetic patients are known to have an exaggerated growth hormone (GH) response to GH-releasing hormone (GHRH), which 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 activity of the autoimmune process involving a key enzyme (glutamic acid 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 acetylcholinesterase inhibitor, pyridostigmine (PD), in patients with type I diabetes mellitus. Twenty non-obese type I diabetic patients and 17 normal subjects underwent an intravenous (IV) injection of 100 μg 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 oral PD 60 minutes before IV injection of 100 μg GHRH. Diabetic subjects 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 peaks 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 of both absolute and peak values, in patients without GADA (n = 6) and in normal subjects. On the contrary, PD failed to enhance the GH response to GHRH in diabetic patients with GADA (n = 6). Our findings suggest that autoimmunity may play a key role in determining the exaggerated GH response to GHRH in type I diabetes mellitus. The mechanism underlying this effect is hypothesized to be the production of antibodies to GAD, a key enzyme in the synthesis of GABA, and in turn a reduced GABAergic stimulatory tone on somatostatin production at the hypothalamic level.

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☆ Supported in part by the Centro Studi e Ricerche di Neuroendocrinologia (Brescia, Italy) and Regione Lombardia (project microalbuminuria no. 53/31.08.1991).

PII: S0026-0495(97)90052-4

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Volume 46, Issue 4 , Pages 382-387, April 1997

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