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

Abstract

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 Västerbotten 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 = 185) [corrected] and diabetes (n = 18), i.e. abnormal OGTT (n = 203) [corrected], had higher GAD65Ab [corrected] index compared with those with normal OGTT (p = 0.026) [corrected]. 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.