Clinical and genetic characteristics of diabetic patients with high-titer (>10,000 U/ml) of antibodies to glutamic acid decarboxylase.
We investigated the clinical aspects and genetic background of 13 diabetic patients with high-titers (>10,000 U/ml) of anti-glutamic acid decarboxylase antibody (Group A) and compared these 28 middle-aged (35-51 years, Group B) and 13 elderly (66-79 years, Group C) patients with anti-GAD(+) (<1100 U/ml) who were diagnosed initially as having type 2 diabetes. The mean age and mean age at onset of Group A were 70.8 +/- 3.9 years (range, 64-78) and 50.4 +/- 5.4 years (range, 43-61), respectively. In Group A, the prevalence of insulin-deficient patients was significantly lower (30.8%, 4 of 13) than in Group C (96.3%, 27 of 28, P < 0.001). Patients in Group A had a significantly longer interval between the clinical onset of diabetes to initiation insulin therapy (21.8 +/- 2.3 years) compared to patients in both Group B (1.8+/-1.1 years, P < 0.001) and Group C (14.8 +/- 7.1 years, P = 0.049). The frequency of DRB1*0405-DQB1*0401/DRB1*1502-DQB1*0601 or DRB*1501-DQB*0602 heterozygous genotypes in Group A (53.8%, 7 of 13) was significantly higher than in both Group B (3.6%, 1 of 28, P < 0.01) and Group C (7.7%, 1 of 13, P < 0.05). Compared with Group B, Group A had an increased frequency of the TNFA-U01 haplotype and the IL-10 -592 C allele (TNFA-U01; 53.8% versus 30.4%, P = 0.05 and IL-10 -592 C; 57.7% versus 33.9 %, P = 0.042). All sera from Group A reacted with GAD(65) protein on Western blots. We conclude that adult-onset diabetic patients with a high-titer of anti-GDAab differ from patients with latent autoimmune diabetes mellitus in adult (LADA) with respect to beta-cell function, cellular autoimmunity and genetic background. Our study also showed that high-titers of antibodies to glutamic acid decarboxylase (anti-GADab) were not predictive of later development of insulin deficiency in adult and/or elderly patients with type 2 diabetes. Furthermore, our results suggest that HLA-DRB1*1502-DQB1*0601 or DRB1*1501-DQB1*0602/DRB1*0405-DQB1*0401 heterozygous genotypes may be associated with high production of anti-GADab that recognizes the linear epitope(s) on the GAD(65) protein.
Ishii
Michiyo
M
Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Japan.
Hasegawa
Goji
G
Fukui
Michiaki
M
Obayashi
Hiroshi
H
Ohta
Mitsuhiro
M
Ogata
Masakazu
M
Yoshioka
Keiji
K
Kitagawa
Yoshihiro
Y
Nakano
Koji
K
Yoshikawa
Toshikazu
T
Nakamura
Naoto
N
D000328:Adult; D017668:Age of Onset; D000368:Aged; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000235:genetics* / Q000276:immunology*; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D007328:Insulin / Q000627:therapeutic use; D007564:Japan; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction
D001323:Autoantibodies; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D007328:Insulin; D005968:Glutamate Decarboxylase