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.

我们旨在阐明关于1型或2型糖尿病的日本儿童和青少年糖尿病进展的致病因素。至于1型糖尿病，已经研究了92例患者。具有GAD抗体的患者很可能具有残留的β细胞功能。 LA-2抗体的测量改善了1型糖尿病的诊断。由于成年患者的LA-2抗体的检测明显低于儿童发作的患者，因此IA-2可能是急性发作糖尿病的标志。到目前为止，我们还没有通过HLA基因型来区分任何临床特征，包括对总糖尿病的进展率，与自身抗体的检测和发病年龄的关联。与IDDM7有关的神经胶/BetA2基因中AlA45THR多态性的频率，与非糖尿病对照相比，儿童发作的1型患者为16.4％。由于成人发病的1型患者的频率为25％，因此注意到三组频率的统计学显着差异。我们建议，除日本1型糖尿病中的自身免疫机制以外，神经dibeta2基因中的ALA45THR多态性可能是致病因素之一。还通过最小的模型分析评估了日本肥胖青少年中2型糖尿病的致病因素。 2型糖尿病的早期表现在发作时偶尔出现酮症，这可能是由于β细胞功能障碍对葡萄糖的葡萄糖功能障碍，这是由于相对较低的第一阶段胰岛素对胰岛素敏感性降低的反应以及日本肥胖者中低葡萄糖效率的相对较低的胰岛素反应所证明的。在本研究的日本模型中，肥胖以外的其他病原因素可能会提供一些线索，以更好地理解对青少年，早期，肥胖的2型糖尿病及其严重性的进展。