Current aspects on the clinical immunology and genetics of autoimmune diabetes in Japan

Japan is one of the countries with lowest incidence rate of childhood type 1 diabetes in the world, averaging 2.4 cases/100,000/year. However, it appears that the prevalence of type 1 diabetes in adulthood is more than twice compared to childhood patients. There are at least three clinical subtypes of type 1 diabetes in Japan, i.e. acute-onset, slow-onset, and fulminant type 1 diabetes. Fulminant type 1 diabetes is a unique subtype of type 1 diabetes that accounts for about 20% of acute-onset type 1 diabetes, and is rare in childhood in Japan. Furthermore, the slow-onset form of type 1 diabetes might be a major subtype of disease in adulthood. In patients with acute-onset type 1 diabetes, about 90% of patients express at least one of GADAbs, IAA, and IA-2Abs at disease onset. Slow-onset form of type 1 diabetes is diagnosed as having type 2 diabetes at disease onset, which is referred as “latent autoimmune diabetes in adults (LADA)”, “GADAb+ type 2 diabetes”, or “slowly progressive type 1 diabetes”. The prevalence of GADAbs in adulthood patients with type 2 diabetes without insulin therapy is 3–4%, and is higher in the patients with shorter duration of diabetes. Although high levels of GADAbs are one of the predictive markers for future insulin requirement, there are a certain number of patients with high titer of GADAbs who do not progress to insulin dependency for many years, and the predictive value of GADAbs positivity for future insulin requirement is estimated about 67% by Baye's theory. Thus, accurate predictive strategies of future insulin deficiency in LADA patients using autoantibody epitope analysis, genetic determination, or T cell assay are needed for the effective immune intervention.