Chuang L M, Lin C Y, Wu H P, Tsai W Y, Tai T Y, Lin B J
Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei.
Clin Endocrinol (Oxf). 1997 Oct;47(4):455-61. doi: 10.1046/j.1365-2265.1997.2851090.x.
Anti-GAD65 antibody has been studied widely in patients with insulin-dependent diabetes mellitus (IDDM) in many different populations. However, the prevalence of GAD65 autoantibody has not been assessed in Taiwanese patients with IDDM. We therefore characterized GAD65 antibody and investigated the effect of HLA-DR phenotypes on GAD65 autoimmunity and other clinical characteristics in Taiwanese subjects with IDDM.
Two hundred and twenty-five patients (male 102, female 123) with IDDM were recruited. The diagnostic criteria for IDDM were age of onset before 30 years, presence of diabetic ketoacidosis, and insulin-dependency within 3 years of onset. We employed a radioligand method to detect GAD65 antibody. HLA-DR typing was performed by the PCR-SSO techniques. Plasma C-peptide and anti-thyroid microsomal antibody were also measured.
The prevalence of GAD65 antibody according to duration of disease were 50/91 (54.9%), 37/95 (38.9%), 8/24 (33%), and 3/15 (20%) among the groups of duration < or = 5, 6-10, 11-15, and > 15 years, respectively (p = 0.0011). There were no significant differences between GAD(+) and GAD(-) patients in age of onset (11.5 +/- 6.5 and 11.6 +/- 13.4 years, respectively), gender distribution (male:female 39:59 and 58:69, respectively) and percentage with residual beta cell function (38.8% and 29.1%, respectively). Multiple regression analysis revealed that duration of IDDM correlated inversely with residual beta cell function. Earlier onset of IDDM correlated with a loss of beta cell function and a HLA-DR phenotype containing DR3/4, DR3/3 or DR3/9.
Prevalence of GAD65 autoantibody among Taiwanese subjects with IDDM was negatively correlated with duration of disease. Different determinants in the HLA-DR locus contributed to the clinical onset of IDDM but not to GAD autoimmunity.
在许多不同人群中，已对胰岛素依赖型糖尿病（IDDM）患者的抗谷氨酸脱羧酶65（GAD65）抗体进行了广泛研究。然而，尚未对台湾IDDM患者中GAD65自身抗体的患病率进行评估。因此，我们对台湾IDDM患者的GAD65抗体进行了特征分析，并研究了HLA-DR表型对GAD65自身免疫及其他临床特征的影响。
招募了225例IDDM患者（男性102例，女性123例）。IDDM的诊断标准为发病年龄在30岁之前、存在糖尿病酮症酸中毒以及发病3年内依赖胰岛素。我们采用放射性配体法检测GAD65抗体。通过聚合酶链反应-序列特异性寡核苷酸（PCR-SSO）技术进行HLA-DR分型。还测量了血浆C肽和抗甲状腺微粒体抗体。
根据病程，病程≤5年、6 - 10年、11 - 15年以及＞15年组中GAD65抗体的患病率分别为50/91（54.9%）、37/95（38.9%）、8/24（33%）和3/15（20%）（p = 0.0011）。GAD（+）和GAD（-）患者在发病年龄（分别为11.5±6.5岁和11.6±13.4岁）、性别分布（男性:女性分别为39:59和58:69）以及残余β细胞功能百分比（分别为38.8%和29.1%）方面无显著差异。多元回归分析显示，IDDM病程与残余β细胞功能呈负相关。IDDM发病较早与β细胞功能丧失以及含有DR3/4、DR3/3或DR3/9的HLA-DR表型相关。
台湾IDDM患者中GAD65自身抗体的患病率与病程呈负相关。HLA-DR基因座中的不同决定因素导致IDDM的临床发病，但与GAD自身免疫无关。
