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.

我们的目的是阐明日本儿童和青少年 1 型或 2 型糖尿病进展为糖尿病的致病因素。至于1型糖尿病，已对92名患者进行了研究。具有GAD抗体的患者很可能有残留的β细胞功能。 IA-2抗体的测量改善了1型糖尿病的诊断。由于成年发病患者中IA-2抗体的检出率显着低于儿童期发病患者，因此IA-2可能是急性发病糖尿病的标志物。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，包括进展为完全糖尿病的比率、与自身抗体检测的关联以及发病年龄。 NeuroD/BETA2 基因中与 iddm7 相关的 Ala45Thr 多态性频率在儿童期发病的 1 型患者中为 16.4%，而在非糖尿病对照中为 9.5%。由于 1 型患者成人发病的频率为 25%，因此三组之间的频率存在统计学上的显着差异。我们认为NeuroDIBETA2基因的Ala45Thr多态性可能是日本1型糖尿病除自身免疫机制之外的致病因素之一。还通过胰岛素改良频繁采样静脉葡萄糖耐量试验和最小模型分析来评估日本肥胖青少年进展为 2 型糖尿病的致病因素。 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，这一点表现为对胰岛素敏感性下降的第一相胰岛素反应相对较低，以及日本肥胖青少年的低血糖有效性。本研究的日本模型中除肥胖之外的这些致病因素可能为更好地了解青少年早发肥胖 2 型糖尿病的进展及其严重程度提供一些线索。