Clinical, autoimmune, and genetic characteristics of adult-onset diabetic patients with GAD autoantibodies in Japan (Ehime study)

OBJECTIVE - To characterize the clinical, autoimmune, and genetic features in Japanese adult-onset diabetic patients with GAD autoantibodies. RESEARCH DESIGN AND METHODS - GAD autoantibodies (GADab) were screened in 4,980 diabetic patients with age of onset >20 years in the hospital-based Ehime Study, and the GADab-positive (GADab) patients were then divided into two groups according to their insulin secretion and compared with nondiabetic subjects. The insulin-deficient, state was defined as <0.33 nmol/l serum C-peptide (CPR) at 2 h postprandial or 6 min after a 1-mg glucagon load. RESULTS - GADab was detected in 188 (3.8%) of the 4,980 diabetic patients tested. Of these patients, 72 (38.3%) were classified as insulin deficient, 97 (51.6%) were classified as non-insulin deficient, and 19 (10.1%) were unclassified. The GADab(+) insulin-deficient patients were characterized by young age at onset of diabetes, low BMI, low maximum BMI, and high levels of HbA(1c). The prevalence of 1A-2 autoantibodies and thyrogastric autoandbodies in the GADab(+) insulin-deficient patients were significantly higher than those in the GADab non-insulin-deficient patients (P < 0.05). GADab(+) patients With insulin deficiency had increased frequencies of HLA DRB1*0405-DQB1*0401, *0802-*0302, and *0901-*0303 haplotypcs, whereas the frequency of only HLA DRB1*0405-DQB1*0401 was increased in the case of GADab(+) noninsulin-deficient patients. Of note is the fact that the GADab(+) non-insulin-deficient group did not differ from healthy control subjects with respect to type I diabetes protective haplotype HLA CONCLUSIONS - We conclude that GADab(+) non-insulin-deficient patients differ from GADab(+) patients with insulin deficiency with respect to clinical characteristics, humoral autoimmunity to other organ-specific autoantibodies, as well as HLA class II genes.