Diagnostic significance of antibodies to glutamic acid decarboxylase in Japanese diabetic patients with secondary oral hypoglycemic agents failure.
Some non-insulin-dependent diabetes mellitus (NIDDM) patients are positive for antibodies to glutamic acid decarboxylase (anti-GAD), and they tend to develop insulin deficiency. The aim of this study was to evaluate the prevalence of anti-GAD in NIDDM with secondary failure of sulfonylurea agents (NIDDM-SF) and to investigate the diagnostic significance of seropositivity for anti-GAD in NIDDM-SF patients by evaluating human leukocyte antigen (HLA)-DRB1 alleles concurrently. The prevalence of anti-GAD in NIDDM-SF, NIDDM, and new-onset (within 1 year after onset) insulin-dependent diabetes mellitus (IDDM) was 9.3% (39/420), 3.1% (12/392), and 65.0% (13/20), respectively. Pancreatic beta cell function deteriorated in NIDDM-SF patients positive for anti-GAD. HLA-DRB1 allele typing revealed that NIDDM-SF patients positive for anti-GAD were significantly associated with DRB1*0901 (RR = 2.81, P < 0.01), which is one of the susceptible alleles to IDDM. Shorter interval before development of secondary failure and insulin deficiency were significantly associated with the presence of DRB1*0901 (P < 0.05) in NIDDM-SF patients positive for anti-GAD. In conclusion, nearly 10% of NIDDM-SF patients are positive for anti-GAD, suggesting that an autoimmune mechanism might play an important role in the pathogenesis of NIDDM-SF patients. In addition, a combination of serological marker (anti-GAD) and genetic marker (HLA-DRB1) is useful for predicting clinical course of NIDDM patients with secondary failure of sulfonylurea agents.
Fukui
M
M
The First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Kyoto, 602, Japan.
Nakano
K
K
Maruya
E
E
Saji
H
H
Ohta
K
K
Ohta
M
M
Obayashi
H
H
Mori
H
H
Kajiyama
S
S
Wada
S
S
Shigeta
H
H
Kitagawa
Y
Y
Nakamura
N
N
Kondo
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D000906:Antibodies / Q000097:blood; D002096:C-Peptide / Q000097:blood / Q000652:urine; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000175:diagnosis*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy*; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D013453:Sulfonylurea Compounds / Q000008:administration & dosage*; D017211:Treatment Failure
D000906:Antibodies; D002096:C-Peptide; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D005968:Glutamate Decarboxylase