Multiple organ-specific autoantibodies in patients with phenotypic type 2 diabetes in China: a post-hoc analysis of the China National Diabetes and Metabolic Disorders Study

Abstract Background In the China National Diabetes and Metabolic Disorders Study, age-standardised prevalence of total diabetes was 9·7%, accounting for 92·4 million adults, in China in 2010. Using clinical data and serum samples from this study, we aimed to investigate the prevalence of several organ-specific autoantibodies in patients with phenotypic type 2 diabetes. Methods This study included a nationally representative sample of 46 239 adults aged 20 years or older from 14 provinces and municipalities. After an overnight fast, participants had an oral glucose tolerance test. Previously diagnosed diabetes was self-reported. We randomly selected 4671 patients with diabetes and 1002 individuals with normal glucose tolerance as controls. Participants were screened centrally for glutamic acid decarboxylase autoantibodies (GAD-Ab), protein tyrosine phosphatase-like protein autoantibodies (IA2-Ab), and zinc transporter isoform 8 autoantibodies (ZnT8-Ab) using validated methods of the Islets Autoantibody Standardization Program 2012. We then assayed for thyroid peroxidase autoantibodies (TPO-Ab), tissue transglutaminase autoantibodies (tTG-Ab), and 21-hydroxylase autoantibodies (21-OH-Ab) in patients with islet autoantibody-positive diabetes (n=175), in randomly selected age-matched and sex-matched patients with islet autoantibody-negative diabetes (n=3052 for TPO-Ab, n=525 for tTG-Ab, and n=525 for 21-OH-Ab), and in individuals with normal glucose tolerance (n=954 for TPO-Ab, n=200 for tTG-Ab, and n=200 for 21-OH-Ab). We used multiple logistic regression analysis to determine the risk factor of each autoantibody. Ethics approval was granted by the Second Xiangya Hospital of Central South University, and all participants provided written informed consent. Findings After adjustment for age and sex using results from the national population census, the standardised prevalence of autoimmune diabetes was 6·0% in all patients with diabetes, which corresponded to about 6 million adults in China. In patients with diabetes, the adjusted antibody positivity was 3·6% for GAD-Ab, 1·2% for IA2-Ab, and 1·5% for ZnT8-Ab. In those with autoimmune diabetes, the adjusted antibody positivity was 16·3% for TPO-Ab, 2·1% for tTG-Ab, and 1·8% for 21-OH-Ab. In patients with islet autoantibody-negative diabetes, the adjusted positivity was 10·2% for TPO-Ab, 0·3% for tTG-Ab, and 0·5% for 21-OH-Ab. In Chinese adults with autoimmune diabetes, those positive for GAD-Ab had a high risk for TPO-Ab positivity (odds ratio 2·39, 95% CI 1·35–4·24; p=0·0031) and tTG-Ab positivity (6·983, 1·24–39·22; p=0·027), and those positive for IA2-Ab had a high risk for tTG-Ab positivity (19·05, 3·14–115·61; p=0·0010). Patients positive for TPO-Ab were at high risk of being positive for 21-OHAb (7·48, 1·44–38·74; p=0·016) and vice versa (7·21, 1·35–38·45; p=0·021). Of note, women had a high risk for TPO-Ab positivity compared with men (3·83, 2·20–6·68; p Interpretation Patients positive for islet autoantibodies have a high risk for other organ-specific autoimmune diseases. Screening of TPO-Ab and tTG-Ab in Chinese individuals with autoimmune diabetes should be considered a priority. Funding National Key Technology Ru0026D Program (2012BAI02B04), the Grant of National Clinical Research Center for Metabolic Diseases (2013BAI09B12), the Program for Changjiang Scholars and Innovative Research Team in University (IRT1195), and the Key Project of Chinese Ministry of Education (113050A).