title: Glutamic acid decarboxylase antibody positivity is associated with an impaired insulin response to glucose and arginine in nondiabetic patients with autoimmune thyroiditis.
abstract: To study whether antibodies to glutamic acid decarboxylase (GADab) are associated with subclinical beta-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 (AIR(14): 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.
authors.affiliation: Department of Endocrinology, University of Lund, S-205 02 Malmö, Sweden.
authors.forename: A L
authors.initials: AL
authors.lastname: Lethagen
authors.forename: U-B
authors.initials: UB
authors.lastname: Ericsson
authors.forename: B
authors.initials: B
authors.lastname: Hallengren
authors.forename: L
authors.initials: L
authors.lastname: Groop
authors.forename: T
authors.initials: T
authors.lastname: Tuomi
mesh_terms: D000328:Adult; D000368:Aged; D000906:Antibodies / Q000032:analysis*; D001120:Arginine / Q000494:pharmacology*; D002096:C-Peptide / Q000097:blood; D002908:Chronic Disease; D005260:Female; D005500:Follow-Up Studies; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000494:pharmacology*; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006801:Humans; D007275:Injections, Intravenous; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D007515:Islets of Langerhans / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D013967:Thyroiditis, Autoimmune / Q000276:immunology* / Q000503:physiopathology*
chemical_list: D000906:Antibodies; D002096:C-Peptide; D007328:Insulin; D005934:Glucagon; D001120:Arginine; D005968:Glutamate Decarboxylase; D005947:Glucose