The purpose of this project is to identify the determinants of non-insulin-dependent diabetes (NIDDM) and other chronic diseases in the Pima Indians, and elucidate their natural history. Genetic and environmental risk factors for NIDDM have been studied. The residents of the study area, approximately 5000 people, have participated in a longitudinal population study since 1965, allowing observations of the natural history of diabetes mellitus. Risk factors for obesity, hypertension, and nephropathy are also studied, along with the relationships of these diseases to diabetes and their effects on mortality rates. The genetics of diabetes is studied by means of family studies and relationships of genetic markers to disease. The roles of obesity, serum insulin concentrations, impaired glucose tolerance, occupational and leisure-time physical activity and diabetes in relatives are assessed. Impaired glucose tolerance (IGT) is a well-established risk factor for diabetes. In all populations, the degree of hyperglycemia (fasting or post-load) and obesity (by body mass index or circumference measures) predicted the conversion from IGT to diabetes. The effects of age differed between populations - those with the highest rates had the highest incidence rates in middle adult years whereas in the other populations rates were positively associated with age (and highest in the oldest subjects). This is consistent with our previous hypothesis that in high risk populations such as the Pimas, much of the disease is due to genetic susceptibility and by the oldest ages most of the susceptible people are already diabetic, resulting in a lower incidence rate. Evidence accumulates on the importance of conditions early in life on risk of diabetes in adulthood. In addition to our previous findings that maternal diabetes in pregnancy and both high and low extremes of birth weight predict type 2 diabetes in adulthood, we have recently found that bottle feeding of infants during their first two months also places them at increased risk of diabetes.