Evidence of diabetes-specific autoimmunity in obese subjects with normal glucose tolerance

Recently, significant attention has been paid to the possible activation of an autoimmune response in the presence of obesity. The aim of this study was to evaluate and compare the frequencies of autoantibodies typical of autoimmune diabetes in obese patients with normal glucose tolerance (NGT), obese patients with type 2 diabetes (T2D) and controls. We also evaluated the presence of immunoreactivity to Hashimoto's thyroiditis and autoimmune gastritis.

Consecutive sera from obese patients, 444 with NGT, 322 with T2D, and 212 controls were analysed by radioimmunoassay or enzyme-linked immunosorbent assay for glutamic acid decarboxylase, protein tyrosine phosphatase islet antigen-2 (IA-2)_IC and IA-2_(256-760) , islet beta-cell zinc cation transporter (ZnT8), thyroid peroxidase, and anti-parietal cell autoantibodies.

Altogether the presence of organ-specific autoantibodies was significantly more frequent in obese patients with NGT (128/444, 28.5%) and obese with T2D (79/322, 24.5%) than in controls (36/212, 17%; P = 0.002). Thyroid peroxidase immunoreactivity was prevalent in all groups of subjects investigated. The frequencies of diabetes-specific autoantibodies were slightly higher in obese patients with NGT (20/444, 4.5%) than in obese with T2D (12/322, 3.7%) and controls (4/212, 1.9%). The anti IA-2_(256-760) was the most frequent islet autoantibody in obese subjects with NGT (14/20, 70%).

We observed significant evidence of immunoreactivity specific to diabetes, thyroid, and gastric-parietal cells in obese patients with NGT. The relatively higher frequency of the diabetes-related IA-2_(256-760) autoantibodies in obese patients with NGT may suggest that this autoantibody could be associated with obesity the presence of obesity itself.