Prevalence of Glutamic Acid Decarboxylase Antibody Positivity and its Association with Insulin Secretion and Sensitivity in Autoimmune Thyroid Disease: A Pilot Study

Abstract

Type 1 diabetes and autoimmune thyroid disease are commonly associated. Few studies have addressed islet-cell autoimmunity and its relation with glucose homeostasis in Hashimoto's thyroiditis. The aims of this study were: (1) to determine the prevalence of islet-cell autoimmunity, and (2) to compare insulin sensitivity and secretion patterns between normal glucose tolerant glutamic acid decarboxylase antibodies (GA-D-Ab) positive and negative patients with Hashimoto's thyroiditis. Two hundred fifty-three consecutive patients with Hashimoto's thyroiditis were recruited. After excluding 38 patients with diabetes mellitus, 215 were screened for presence of GAD-Ab. Nine GAD-Ab positive and 8 age, sex and body mass index (BMI) matched GAD-Ab negative patients from the same cohort were included. Frequently sampled intravenous glucose tolerance tests (FSIGTT) were applied. Using glucose and insulin data from FSIGTT, fasting glucose to insulin ratio, HOMA-IR and HOMA-beta-cell function, using the minimal model analysis (MIN-MOD) program, the first phase insulin secretion in response to glucose, the insulin sensitivity index and glucose sensitivity index were calculated. Eleven patients were positive for GAD-Ab (5.1%). There was no difference in any insulin sensitivity or secretion parameters between the GAD-Ab positive and negative patients. Our results suggest that the prevalence GAD-Ab in Hashimoto's thyroiditis is around 5%. GAD-Ab antibody positivity per se does not appear to be associated with any disturbances in insulin sensitivity or insulin secretion in this specific population. The presence of islet-cell autoimmunity does not seem to influence insulin secretion or action in normal glucose tolerant subjects with Hashimoto's thyroiditis in this pilot study. Whether the presence of GAD-Ab per se or along with other antibodies impairs insulin dynamics or predicts the development of diabetes in autoimmune thyroiditis remains to be determined in future studies.