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Glutamic Acid Decarboxylase Antibody Positivity Is Associated with an Impaired Insulin Response to Glucose and Arginine in Nondiabetic Patients with Autoimmune Thyroiditis

Department of Endocrinology (Å.L.L., U.-B.E., B.H., L.G., T.T.), University of Lund, S-205 02 Malmö, Sweden; and Department of Medicine (T.T.), Helsinki University Central Hospital, FIN-00029 Helsinki, Finland

Address all correspondence and requests for reprints to: Tiinamaija Tuomi, M.D., Wallenberg Laboratory, Department of Endocrinology, University of Lund, S-205 02 Malmö, Sweden. E-mail: Tiinamaija. . Tuomi{at}endo.mas.lu.se

Abstract

To study whether antibodies to glutamic acid decarboxylase (GADab) are associated with subclinical ß-cell damage and impaired insulin secretion, we screened 441 nondiabetic patients with autoimmune thyroiditis (AT) for GADab, and 15 (3.4%) were found positive. Antibodies to IA-2 were found in two GADab+ and one GADab- patients. We matched 11 GADab+ and 13 GADab- AT patients who were euthyroid on thyroxin supplementation, and 13 control subjects for sex, age, and body mass index and measured insulin, C-peptide, and glucagon response to glucose and arginine at three blood glucose concentrations (fasting, 14 mmol/liter, >25 mmol/liter). In the fasting state, all groups had similar blood glucose concentration and HbA1c level, but the serum insulin concentration was higher in the AT patients compared with the control subjects (P < 0.04). The acute insulin response to arginine was lower in GADab+ than in GADab- thyroiditis subjects at glucose concentration of 14 and >25 mmol/liter (AIR₁₄: 76.8 ± 52.0 vs. 158.2 ± 118.2 mU/liter, P = 0.040; AIR_>25: 84.3 ± 64.4 vs. 167.9 ± 101.5 mU/liter, P = 0.035). In conclusion, GADab were associated with a decreased insulin secretion capacity in nondiabetic subjects with thyroiditis, which suggests that GADab positivity could be a marker of subclinical insulitis.