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

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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.