Heterogeneous relationship of early insulin response and fasting insulin level with development of non-insulin-dependent diabetes mellitus in non-diabetic Japanese subjects with or without obesity

The aim of this study was to investigate the association of insulin secreti on and insulin resistance with the development of non-insulin-dependent dia betes mellitus (NIDDM) in obese (body mass index (BMI) greater than or equa l to 25 kg/m(2)) and non-obese Japanese. Subjects were selected from person s 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 yea rs (mean 4.5 years). The fasting insulin level and the homeostasis model in sulin resistance index (HOMA-R = fasting glucose [mmol/l] x fasting insulin [mu U-ml]/22.5) were used as the index of insulin resistance, and iusulino genic index (the ratio of increment of insulin to that of blued glucose 30 min after glucose load) as a measure of early insulin response. Cox's propo rtional 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. Sea, fami ly history, fasting insulin level and HOMA-R were not predictive of develop ing diabetes. In subgroup analysis, the same variables as in the whole grou p were predictors in non-obese, whereas only FBG and 2-h BG predicted diabe tes in obese subjects. Fasting insulin level and HOMA-R were not predictive of diabetes both in non-obese and obese subjects. Eleven obese subjects, w ho developed diabetes despite a normal initial insulinogenic index, had sig nificantly 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 g roup of diabetes patients may start with insulin resistance, especially obe se subjects. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.