We have been conducting the Hawaii-Los Angeles-Hiroshima Study since 1970, mainly to determine the effects of environmental changes on various diseases by comparing Japanese-Americans with native Japanese subjects. Japanese-Americans living in Hawaii and Los Angeles are originated mainly from Hiroshima, Japan and are genetically identical with native Japanese. Through this study, we made several clear observations about Japanese-Americans. First, Japanese-Americans were highly exposed to a westernized lifestyle ; in other words, a relatively high fat and simple carbohydrate diet with low physical activity as compared to native Japanese. Second, the prevalence of type 2 diabetes among Japanese-Americans and death from ischemic heart disease among Japanese-American diabetic patients were higher. Third, the serum fasting insulin level as well as the insulin level after a glucose load, was higher among Japanese-Americans, even when the serum glucose levels were not statistically different as compared to native Japanese. Accordingly, Japanese-Americans were thought to have a high insulin resistance status. However, the initial insulin response after a glucose load was low, which was more similar to Japanese people than to Caucasians. Fourth, the total cholesterol and triglyceride levels were higher among Japanese-Americans. These results are supposed to be derived from the insulin resistant status by the westernization of lifestyle, as well as from the weakness of pancreatic β cell function that is supposed to be genetically regulated among Japanese. In conclusion, it appears that for genetically Japanese people, environmental factors are important for the development of metabolic diseases such as diabetes mellitus and cardiovascular disease.