GLUCOSE-TOLERANCE, INSULIN-SECRETION, AND INSULIN SENSITIVITY IN NONOBESE AND OBESE JAPANESE SUBJECTS

OBJECTIVE - To investigate the relative contributions of insulin secre tion 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 we re classified according to the World Health Organization (WHO) criteri a (normal glucose tolerance [NGT], impaired glucose tolerance [IGT], a nd diabetes). Early phase insulin secretion was assessed by the insuli nogenic 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 obes e subjects with IGT and NGT were not statistically different. Subjects with diabetes showed a significant decline in early-phase and total i nsulin secre tion and a significantly higher level of insulin resistan ce than did subjects with IGT. When the fasting plasma glucose (FPG) e xceeded 100 mg/dl, early phase insulin decreased progressively. The gr aphed 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 resist ance associated with the progression of glucose intolerance was simila r in both the nonobese and obese subjects. CONCLUSIONS - The worsening from NGT to IGT in Japanese subjects may be associated with a decreas e in early-phase insulin secretion in nonobese as well as in obese sub jects. Hyperinsulinemia in IGT is not common. We suggest that impaired early-phase insulin secretion may be the initial abnormality in the d evelopment of glucose intolerance in Japanese people. Insulin resistan ce may be a consequence of hyperglycemia and/or obesity.