Objective: To explore the insulin resistance and first-phase insulin secretion of beta-cells in normal persons, obese persons with normal glucose tolerance, obese persons with impaired glucose tolerance (IGT) and obese persons with type 2 diabetes (T2DM).
Methods: 75 g oral glucose tolerance test (OGTT) and Bergman's minimal model method of frequently sampled intravenous glucose tolerance test (FSIGTT) with reduced sample number (n = 12) were performed on a total of 151 subjects, 29 normal controls (control group), 44 obese persons with normal glucose tolerance (obesity group), 36 obese persons with IGT (IGT group), and 42 T2DMT patients (T2DM group) to determine the acute insulin response to glucose (AIRg), insulin sensitivity index (S(I)), and glucose effectiveness (S(G)). The disposition index (DI, AIRg X S(I)) was calculated to determine whether AIRg was adequate to compensate for insulin resistance.
Results: The S(I) value of the control group was significantly higher than those of the obesity, IGT, and T2DM groups (all P < 0.01), without significant difference among the latter three groups. The S(G) value of the control group was not significantly different from that of the obesity group, but significantly higher than those of the IGT and T2DM groups (both P < 0.01), without significant difference any 2 groups from the latter two groups. The AIRg of the normal group was similar to that of the IGT group (2.61 mU x L(-1) x min(-1) +/- 0.13 mU.L(-1) x min(-1) vs 2.56 mU x L(-1) x min(-1) +/- 0.25 mU x L(-1) x min(-1)), and significantly lower than that of the obesity group (3.02 mU x L(-1) x min(-1) +/- 0.27 mU x L(-1) x min(-1), P < 0.01) and higher than that of the T2DM group (1.54 mU x L(-1) x min(-1) +/- 0.55 mU x L(-1) x min(-1), P < 0.01). The value of DI was gradually decreased from the sequence of the groups of control, obesity, IGT, and T2DM (3.16 +/- 0.31, 2.65 +/- 0.50, 1.67 +/- 0.54), with significant differences between any two groups (all P < 0.01). Multiple regression analyses with S(I) and AIRg as dependent variables showed that S(I) was negatively correlated with BMI, 2 h glucose level in OGTT, 2 h insulin, triglyceride, and cholesterol (r(2) = 0.589, P < 0.001), and AIRg was positively correlated with BMI, S(G), fasting insulin, and 2 h insulin level and negatively correlated with 2 h glucose, and age (r(2) = 0.515, P < 0.001).
Conclusion: Obese patients with different glucose tolerance have similar degrees of insulin resistance. Acute insulin response is increased in obesity group to compensate for the insulin resistance. Although the acute insulin response in the IGT group is similar to that in the control group, however, the compensation of islet beta cells in the IGT group is significantly decreased as compared with that in the obesity group, leading to glucose intolerance. There is a severe deficiency of acute insulin response to glucose in T2DM group.