Fukui M, Nakano K, Maruya E, Saji H, Ohta K, Ohta M, Obayashi H, Mori H, Kajiyama S, Wada S, Shigeta H, Kitagawa Y, Nakamura N, Kondo M
The First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Kyoto, 602, Japan.
Clin Immunol Immunopathol. 1997 Nov;85(2):182-6. doi: 10.1006/clin.1997.4442.
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 DRB10901 (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 DRB10901 (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.
一些非胰岛素依赖型糖尿病（NIDDM）患者的谷氨酸脱羧酶抗体（抗GAD）呈阳性，并且他们往往会出现胰岛素缺乏。本研究的目的是评估磺脲类药物继发失效的NIDDM（NIDDM-SF）患者中抗GAD的患病率，并通过同时评估人类白细胞抗原（HLA）-DRB1等位基因来研究抗GAD血清阳性在NIDDM-SF患者中的诊断意义。NIDDM-SF、NIDDM以及新发（发病后1年内）胰岛素依赖型糖尿病（IDDM）患者中抗GAD的患病率分别为9.3%（39/420）、3.1%（12/392）和65.0%（13/20）。抗GAD阳性的NIDDM-SF患者的胰岛β细胞功能恶化。HLA-DRB1等位基因分型显示，抗GAD阳性的NIDDM-SF患者与DRB10901显著相关（相对危险度=2.81，P<0.01），DRB10901是IDDM的易感等位基因之一。抗GAD阳性的NIDDM-SF患者中，继发失效和胰岛素缺乏发生前的间隔时间较短与DRB1*0901的存在显著相关（P<0.05）。总之，近10%的NIDDM-SF患者抗GAD呈阳性，提示自身免疫机制可能在NIDDM-SF患者的发病机制中起重要作用。此外，血清学标志物（抗GAD）和遗传标志物（HLA-DRB1）的联合使用有助于预测磺脲类药物继发失效的NIDDM患者的临床病程。
