Glutamate decarboxylase (GAD65) and tyrosine phosphatase-like protein (IA-2) autoantibodies index in a regional population is related to glucose intolerance and body mass index

Aims/hypothesis. Our aims were to investigate the concentrations and prevalence of autoantibodies against the Mr 65.000 isoform of glutamate decarboxylase (GAD65) and the tyrosine phosphatase-like protein (IA-2) in adults and to test the hypothesis that GAD65 and IA-2 autoantibodies in a regional population are related to abnormal oral glucose tolerance. Methods. We analysed serum from 2157 Swedish subjects aged either 30, 40, 50 or 60 years old who, in 1988-1992, participated in the Vasterbotten County Health Project and were subjected to the World Health Organisation (WHO) standard oral glucose tolerance test at entry into the study. Results. We found 23 of 2157 (1.1%) and 17 of 2152 (0.8%) subjects exceeded the 99th centile of GAD65 autoantibody index and IA-2 autoantibody index, respectively. In 18 subjects with diabetic oral glucose tolerance test, GAD65 autoantibody concentrations were higher than in those with normal oral glucose tolerance test (p = 0.02). Subjects with IGT (n = 416) and diabetes (n = 18), i.e. abnormal OGTT (n = 434), had a higher IA-2Ab index compared with those with normal OGTT (p = 0.008). A stepwise multiple logistic regression test showed that the odds ratios for subjects in the highest BMI group to exceed the 95th or 99th GAD65 autoantibody centile were 3.6 (CI 1.4-8.9) and 17.6 (CI 2.6-121.6), respectively. Conclusion/interpretation. GAD65 and IA-2 autoantibodies, are associated with impaired or diabetic glucose tolerance in an adult regional population. This observation together with the association between GAD65 autoantibody concentrations and body mass index indicate a possible relation between islet autoimmunity and beta-cell function abnormalities with obesity and insulin resistance.