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 preval ence of autoantibodies against the Mr 65.000 isoform of glutamate decarboxy lase (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 po pulation are related to abnormal oral glucose tolerance. Methods. We analysed serum from 2157 Swedish subjects aged either 30, 40, 5 0 or 60 years old who, in 1988-1992, participated in the Vasterbotten Count y 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, GAD 65 autoantibody concentrations were higher than in those with normal oral g lucose 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 regr ession test showed that the odds ratios for subjects in the highest BMI gro up 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 wi th impaired or diabetic glucose tolerance in an adult regional population. This observation together with the association between GAD65 autoantibody c oncentrations and body mass index indicate a possible relation between isle t autoimmunity and beta-cell function abnormalities with obesity and insuli n resistance.