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OBJECTIVE -To investigate the relative contributions of insulin secretion and insulin resistance to the development of glucose intolerance in Japanese subjects.RESEARCH DESIGN AND METHODS -A cross-sectional study of 756 Japanese subjects (530 nonobese, 226 obese) was performed. A 75-g oral glucose tolerance test (OGTT) was given, and subjects were classified according to the World Health Organization (WHO) criteria (normal glucose tolerance [NGT], impaired glucose tolerance [IGT], and diabetes). Early-phase insulin secretion was assessed by the insulinogenic index (the ratio of the increment of insulin to that of plasma glucose [PG] 30 min after a glucose load [Delta IRI0-30 min/Delta PG0-30 min]). Total insulin secretion was assessed by mean immunoreactive insulin (IRI) during the OGTT, and insulin resistance was assessed by use of the homeostasis model [HOMA(R)].RESULTS -Early-phase insulin secretion was significantly decreased in IGT, compared with patients with NGT, in both the nonobese and obese subjects (0.70 +/- 0.05 vs. 0.37 +/- 0.03, P < 0.01 and 1.36 +/- 0.19 vs. 0.73 +/- 0.08, P < 0.01, respectively). However, mean IRI and HOMA(R) in both nonobese and obese subjects with IGT and NGT were not statistically different. Subjects with diabetes showed a significant decline in early-phase and total insulin secretion and a significantly higher level of insulin resistance that did subjects with IGT. When the fasting plasma glucose (FPG) exceeded 100 mg/dl, early-phase insulin decreased progressively. The graphed relationship between FPG and mean IRI did not show an inverted U-shape, and mean IRI decreased progressively when FPG exceeded 110-130 mg/dl. The pattern of changes in insulin secretion and insulin resistance associated with the progression of glucose intolerance was similar in both the nonobese and obese subjects.CONCLUSIONS -The worsening from NGT to IGT in Japanese subjects may be associated with a decrease in early-phase insulin secretion in nonobese as well as in obese subjects. Hyperinsulinemia in IGT is not common. We suggest that impaired early-phase insulin secretion may be the initial abnormality in the development of glucose intolerance in Japanese people. Insulin resistance may be a consequence of hyperglycemia and/or obesity.