Clinical and genetic characteristics of GAD-antibody positive patients initially diagnosed as having type 2 diabetes*1

Abstract

The present study was conducted to clarify the clinical and genetic characteristics of the diabetic patients who have antibodies to glutamic acid decarboxylase (GADab) but are diagnosed initially as type 2 diabetes because of the slow progression. Fifty-five GADab+ patients and 137 GADab− patients were recruited. The GADab+ patients were divided into two subgroups according to their antibody titers. The high-titer subgroup (Ab≥20 U/ml) had lower urinary C-peptide concentrations, and was assigned insulin therapy more often than the GADab− patients. In contrast to the high-titer subgroup, clinical parameters in the low-titer subgroup were similar to the GADab− diabetic patients. The urinary C-peptide levels correlated negatively with the GADab titer in the GADab+ patients. Analysis of type 1 diabetes-susceptible HLA alleles revealed high frequencies of the B54 and DRB1*0405 allele, but not the B61 and DRB1*0901 alleles, in the high-titer subgroup, whereas the frequency of the protective DRB1*1502 allele was decreased. The GADab+ patients with the B54 allele had higher GADab titers and lower urinary C-peptide excretion than patients without this allele. These data indicated that patients with a high-GADab titer share the autoimmune background characteristic of type 1 diabetes.