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.

Autoimmune Thyroid Disease Correlates to Islet Autoimmunity on Zinc Transporter 8 Autoantibody: A Cross-Section Study

“…Measurements of GADA and IA-2A are recommended for initial confirmation of the suspected diagnosis of T1DM or for the prediction of T1DM in research settings (26).Our prevalence of either GADA or IA-2A was similar to findings in the previous studies (18,19,(27)(28)(29).While there was a significantly lower frequency and level of either GADA or IA-2A in the AITD patients compared with that in the T1DM patients, the results were still significant higher than in the healthy subjects, thus partly confirmed the findings on GADA of Kawasaki et al (19). Take into consideration the early study from Kawasaki et al(30)which demonstrated that the level of GADA in T1DM with AITD were found to be significantly higher than in patients without AITD, and the recent Chinese study revealing the high level of GADA to be a strong predictor of the development of thyroid autoimmunity in patients with autoimmune diabetes (31), as well as the finding of Lethagen et al (32) that GADA positivity could be a marker of subclinical insulitis in non-diabetic patients with autoimmune thyroiditis, and the strong connection which Brorsson et al (9) figured out that GADA is related to both increasing age and human leukocyte antigen (HLA) DQ2/DR3, we conclude that the presence of GADA may be a marker of concurrent or successive thyroid autoimmunity and islet autoimmunity. Piliaet al (18)observed that IA-2A was significantly prevalent in Sardinian children with autoimmune thyroiditis, which is consistent with our results to some degree, however, their prevalence of GADA showed no significant differences compared with healthy controls.…”

Prevalence of pancreatic autoantibodies in non-diabetic patients with autoimmune thyroid disease and its relation to insulin secretion and glucose tolerance

“…In Swedish patients, GADA was detected in 13% of newly diagnosed GD patients without clinical diabetes mellitus and in 3.4% of HT patients (18,25). In Japanese patients, GADA was found in 6% of GD and 7.9% of HT patients (17) although the time since thyroid disease diagnosis was not reported, and the patients were in different degrees of thyroid function.…”

“…It has been shown that positive GADA HT patients had similar FPG and insulin concentrations than negative GADA subjects; however, when submitted to arginine injection, they showed a decline in the insulin secretory capacity and the glucagon response to arginine (25).…”

GAD65 vaccination: 5 years of follow-up in a randomised dose-escalating study in adult-onset autoimmune diabetes

“…In total, 40/47 patients completed the 5 year study, which included information about adverse events. GADA and IA-2A were determined as previously described [8]. However, after 12 months, only GADA was analysed.…”