Objective: To assess the relationship between the fasting plasma glucose (FPG) concentration and insulin secretion in NGT and IGT subjects. Methods: 531 non-diabetic subjects with NGT (n=293) and IGT (n=238) (310 Japanese and 232 Mexican Americans) received OGTT with measurement of plasma glucose, insulin, and C-peptide every 30 minutes. Insulin secretion rate was determined by plasma C-peptide deconvolution. Insulin sensitivity (Matsuda Index) was measured from plasma insulin and glucose concentrations. The insulin secretion/insulin resistance (IS/IR) or disposition index was calculated as ISR/G ÷ IR. Results: As FPG increased in NGT subjects, the IS/IR index declined exponentially over the range of FPG from 70 to 125 mg/dl. The relationship between IS/IR index and FPG was best fit with the equation: 28.8 exp (-0.036 FPG). For every 28 mg/dl increase in FPG, the IS/IR index declined by 63%. A similar relationship between IS/IR index and FPG was observed in IGT. However, the decay constant was lower than in NGT. The IS/IR index for early phase insulin secretion (0-30 min) was correlated with the increase in FPG in both NGT and IGT (r=-0.43, p<0.0001 and r=-0.20, p=0.001, respectively). However, the correlation between late phase insulin secretion (60-120 min) and FPG was not significant. Conclusions: (1) small increments in FPG, within the "normal" range, are associated with a marked decline in glucose-stimulated insulin secretion; (2) the decrease in insulin secretion with increasing FPG is greater in subjects with NGT than IGT and primarily is due to a decline in early phase insulin secretion.