Impact of differences in fasting glucose and glucose tolerance on the hyperbolic relations between insulin sensitivity and insulin responses

OBJECTIVE - To determine whether the hyperbolic relationship between insulin sensitivity and the acute insulin response to glucose (AIR(g)) exists in subjects with impaired fasting glucose (IFG) or decreased glucose tolerance. RESEARCH DESIGN AND METHODS - We studied 219 healthy subjects (88 male and 131 female subjects, aged 26 - 75 years) with fasting plasma glucose (FPG) < 6.11 mmol/l. Subjects underwent an intravenous glucose tolerance test to determine the insulin sensitivity index (S-1), AlRg, and the glucose disappearance constant (K-g), the latter a measure of intravenous glucose tolerance. RESULTS - S-1 and AIR(g) were inversely related for the entire cohort, and this relationship was not significantly different from hyperbolic. The inverse relationship between S-1 and AIR(g) was not significantly different when compared between groups based on fasting glucose (normal fasting glucose [NFG], FPG < 5.56 mmol/l vs. IFG, FPG 5.56 - 6.11 mmol/l) or by the K-g quartile. However, the curve relating S-1 and AIR(g) was left shifted in the IFG compared with NFG group (P < 0.001) and was progressively more left shifted with decreasing K. (P < 0.001), consistent with decreasing beta-cell function. These changes were not observed for the curves relating S-1 and fasting insulin, suggesting that in the fasting state beta-cell function is maintained even in patients with mild IFG. Finally, the disposition index (DI) (S-1 X AIR(g)) was calculated as a measure of beta-cell function. The DI progressively decreased With increasing FPG, even in the group of subjects classified as NFG. CONCLUSIONS - The inverse relationship between insulin sensitivity and AIR(g) is consistent with a hyperbola not only in subjects with normal glucose tolerance but also with mild IFG or decreased K-g. Based on a hyperbolic relationship, a decrease in beta-cell function can be detected as FPG increases, even in patients who are normal glucose tolerant.