The aim of this study was to investigate the association of insulin secretion and insulin resistance with the development of non-insulin-dependent diabetes mellitus (NIDDM) in obese (body mass index (BMI) > or = 25 kg/m2) and non-obese Japanese. Subjects were selected from persons participating a health survey, and a 100 g oral glucose tolerant test was performed. A total of 1604 non-diabetic subjects were followed for 2-8 years (mean 4.5 years). The fasting insulin level and the homeostasis model insulin resistance index (HOMA-R = fasting glucose [mmol/l] x fasting insulin [microU/ml]/22.5) were used as the index of insulin resistance, and insulinogenic index (the ratio of increment of insulin to that of blood glucose 30 min after glucose load) as a measure of early insulin response. Cox's proportional hazards analysis in the whole group showed that BMI, fasting blood glucose (FBG) and 2-h blood glucose (2-h BG) were positive predictors, and age and insulinogenic index were negative predictors of diabetes. Sex, family history, fasting insulin level and HOMA-R were not predictive of developing diabetes. In subgroup analysis, the same variables as in the whole group were predictors in non-obese, whereas only FBG and 2-h BG predicted diabetes in obese subjects. Fasting insulin level and HOMA-R were not predictive of diabetes both in non-obese and obese subjects. Eleven obese subjects, who developed diabetes despite a normal initial insulinogenic index, had significantly higher BMI, fasting insulin level and HOMA-R, compared with 258 obese subjects who did not develop diabetes. We conclude that most cases of diabetes in Japanese begin with decreased insulin secretion, but a small group of diabetes patients may start with insulin resistance, especially obese subjects.