Clinical, Autoimmune, and Genetic Characteristics of Adult-Onset Diabetic Patients With GAD Autoantibodies in Japan (Ehime Study)

Diabetes Care - Tập 25 Số 6 - Trang 995-1001 - 2002
Haruyo Takeda1, Eiji Kawasaki2, Ikki Shimizu3, Etsushi Konoue4, Masao Fujiyama5, Satoshi Murao6, Kiyonobu TANAKA7, Kennichi Mori8, Yoshinao Tarumi9, Isamu Seto10, Yasuhisa Fujii3, Kenichi Kato3, Shiori Kondo4, Yasuharu Takada7, Nobuaki Kitsuki8, Yukikazu Kaino11, Kaichi Kida11, Naotake Hashimoto12, Yukio Yamane13, Takashi Yamawaki1, Hiroshi Onuma1, Tatsuya Nishimiya1, Haruhiko Osawa1, Yasushi Saitō12, Hideichi Makino1
1Department of Laboratory Medicine, Ehime University School of Medicine, Ehime, Japan
2First Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan
3Ehime Prefectural Hospital, Ehime, Japan
4Matsuyama Red Cross Hospital, Ehime, Japan
5Fujiyama Clinic, Ehime, Japan
6Matsuyama Shimin Hospital, Ehime, Japan
7Saijo Central Hospital, Ehime, Japan
8Ehime Rousai Hospital, Ehime, Japan
9Minami Matsuyama Hospital, Ehime, Japan
10BML, Tokyo, Japan
11Department of Pediatrics, Ehime University School of Medicine, Ehime, Japan
12Second Department of Internal Medicine, Chiba University School of Medicine, Chiba, Japan.
13Juzen General Hospital, Ehime, Japan

Tóm tắt

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 HbA1c. The prevalence of IA-2 autoantibodies and thyrogastric autoantibodies 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 haplotypes, whereas the frequency of only HLA DRB1*0405-DQB1*0401 was increased in the case of GADab+ non–insulin-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 1 diabetes protective haplotype HLA DRB1*1502-DQB1*0601. A total of 13% of the GADab+ patients with diabetes had genotypes comprising the DRB1*1501-DQB1*0602 or *1502-*0601 and were characterized by old age at onset of diabetes, high BMI, resistance to the insulin-deficient state, low titer of GADab, and low frequency of other organ-specific autoantibodies. 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.

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Diabetes Care

Tập 25 Số 6

995-1001

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