Glutamic acid decarboxylase antibody positivity is associated with an impaired insulin response to glucose and arginine in nondiabetic patients with autoimmune thyroiditis.
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.
Lethagen
A L
AL
Department of Endocrinology, University of Lund, S-205 02 Malmö, Sweden.
Ericsson
U-B
UB
Hallengren
B
B
Groop
L
L
Tuomi
T
T
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*
D000906:Antibodies; D002096:C-Peptide; D007328:Insulin; D005934:Glucagon; D001120:Arginine; D005968:Glutamate Decarboxylase; D005947:Glucose