Why is type 1 diabetes uncommon in Asia?

T1D (type 1 diabetes) incidence rates are extremely low in Asian populations. The prevalences of islet-specific autoantibodies are reported to be low compared with Caucasians. Although the clinical and immunologic characteristics of T1D in Asians appear to be different from those of Caucasians, if we apply correct patient definition and standardized methods, the typical T1D patients are very similar, in the immunologic as well as genetic perspectives. Although the association of individual allele seems to be different between populations, if we compare the identical DR-DQ haplotypes, the association and transmission to diabetic offspring were similar for Asians and Caucasians. The high-risk HLA genotypes/haplotypes were found to be independent determinants of diabetes in the first-degree relatives of individuals with T1D, particularly in the presence of autoantibodies. A different genetic susceptibility including a low frequency of high-risk HLA alleles could explain the lower prevalence of islet-specific autoantibodies and the low incidence of T1D, or different genetic and environmental interactions might be involved in the etiology of T1D. It is certain that DR-DQ linkage disequilibrium (LD) is an important factor explaining the difference in T1D incidence in different countries. LD between highly susceptible DRB1 alleles and protective DQB1 alleles, and vice versa, is the major contributing factor to the low incidence of T1D in Asians. We also suggested that different genetic/environmental interactions might operate in the etiology of T1D between Caucasians and Asians. It would be of great help for primary prevention to investigate to what degree genetic determinants influence the well-known regional differences in incidences, since we can identify environmental risk factors that may either initiate the autoimmune process or promote already ongoing beta cell damage in different countries. For this, population-based epidemiological studies are necessary to identify risk determinants that may be useful for primary prevention strategies.