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The pathogenic factors in the development of Japanese childhood-onset diabetes.

日本儿童期糖尿病发病的致病因素。

基本信息

批准号：
09670794
负责人：
AMEMIYA Shin
金额：
$ 1.98万
依托单位：
Yamanashi medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

项目摘要

We aimed to clarify the pathogenic factors for the progression to diabetes in Japanese children and adolescents, regarding type 1 or type 2 diabetes. As for type 1 diabetes, 92 patients have been studied. The patients with GAD antidbody were highly likely to have residual beta-cell function. The measurement of lA-2 antibody improved the diagnosis at type 1 diabetes. Since the detection of lA-2 antibody was significantly lower in the patients of adulthood-onset than in those of childhood -onset, IA-2 may be a marker for acute-onset diabetes. So far we did not differentiate any clinical characteristics by HLA genotypes, including the rate of progression to total diabetes, the association with the detection of autoantibodies, and the age of onset. The frequency of Ala45Thr polymorphism in NeuroD/BETA2 gene, relating to iddm7, -was 16.4% in type 1 patients of childhood-onset in comparison to 9.5% in non-diabetic controls. Since the frequency in type 1 patients of adult-onset was 25%, the statistically significant difference in the frequencies among three groups was noted. We suggest that the Ala45Thr polymorphism in NeuroDIBETA2 gene may be one of the pathogenic factors other than autoimmune mechanism in Japanese type 1 diabetes. The pathogenic factors in the progression to type 2 diabetes in Japanese obese adolescents were also evaluated by insulin-modified frequent sampling intravenous glucose tolerance test with the Minimal Model analysis. The early manifestation of type 2 diabetes with occasional ketosis at the onset may result from the beta-cell dysfunction to glucose demonstrated by the relatively low first-phase insulin response to decreased insulin sensitivity, as well as the low glucose effectiveness in Japanese obese adolescents. These pathogenic factors other than obesity in a Japanese Model of the present study may give some clues for a better understanding of the progression to adolescent, early-onset, obese type 2 diabetes and its severity.

我们的目的是澄清日本儿童和青少年糖尿病进展的致病因素，关于1型或2型糖尿病。对于1型糖尿病，研究了92例患者。GAD抗体阳性患者极有可能存在β细胞功能残留。1A-2抗体的检测提高了对1型糖尿病的诊断。由于成人发病组IA-2抗体的检出率明显低于儿童发病组，IA-2可能是急性发病糖尿病的一个标志物。到目前为止，我们没有区分任何临床特征的HLA基因型，包括进展为总糖尿病的速度，与自身抗体的检测，和发病年龄的关联。与iddm 7相关的NeuroD/BETA 2基因Ala 45 Thr多态性在儿童期发病的1型糖尿病患者中的频率为16.4%，而在非糖尿病对照组中的频率为9.5%。由于成人发病的1型患者的频率为25%，因此注意到三组之间的频率具有统计学显著性差异。提示NeuroDIBETA 2基因Ala 45 Thr多态性可能是日本1型糖尿病自身免疫机制以外的致病因素之一。在日本肥胖青少年发展为2型糖尿病的致病因素也进行了评估，胰岛素改良的频繁采样静脉葡萄糖耐量试验的最小模型分析。2型糖尿病的早期表现（发病时偶尔出现酮症）可能是由于β细胞对葡萄糖的功能障碍所致，表现为第一时相胰岛素对胰岛素敏感性降低的反应相对较低，以及日本肥胖青少年的葡萄糖有效性较低。在本研究的日本模型中，这些除肥胖外的致病因素可能为更好地了解青少年早发性肥胖2型糖尿病及其严重程度的进展提供一些线索。