Current knowledge of Japanese type 1 diabetic syndrome

The Japanese have one of the lowest incidence of childhood type 1 diabetes in the world, but the incidence of this disease is clearly increasing within the Japanese population, as reported in several European countries. Latent autoimmune diabetes mellitus in adult (LADA) patients are also likely to have a lower incidence compared to Caucasians. Among the non-autoimmune (type 1B) diabetes in Japanese adults, there exists a novel subtype of type 1 diabetes characterized by extremely rapid onset and pancreatic exocrine inflammation. HLA and non-HLA gene associations to type 1 diabetes may vary depending on ethnic origin. Highly susceptible HLA haplotypes of type 1 diabetes observed in Caucasian patients are not found in Japanese patients, while protective HLA haplotypes are similar. Association studies of non-HLA genes have identified several candidate genes that influence the heterogeneity of disease phenotypes as well as disease susceptibility to type 1 diabetes. The INS-VNTR gene or polymorphisms of MICA gene are associated with susceptibility, whereas a certain allele of MICA gene and IL-10 gene polymorphism are associated with clinical heterogeneity of the disease. An expression of multiple autoantibodies to a biochemically determined autoantigen confers a high risk for progression to type 1 diabetes. The combined evaluation of multiple autoantibodies is more sensitive than is ICA testing for the diagnosis of type 1 diabetes. A high titer of GAD autoantibody has the predictive value of future insulin deficiency in patients with LADA. For accurate predictive strategies of future insulin deficiency, combinational multiple autoantibodies analysis or genetic determination should be considered for effective immune intervention.