Objective: We determined whether variations in fasting plasma glucose (FPG) within the nondiabetic range represent differences in insulin action or secretion.

Subjects and methods: Using results of the 75-g oral glucose tolerance test, we classified 39 adults (body mass index range 20-56 kg/m2) as having normal fasting glucose (NFG, <100 mg/dl, n = 24) or impaired fasting glucose (IFG, 100-125 mg/dl, n = 15). The NFG group was subdivided into low-NFG (<90 mg/dl, n = 11) and high-NFG (90-99 mg/dl, n = 13). The 2-h oral glucose tolerance test plasma glucose value was used to assign normal or impaired glucose tolerance (IGT) status. Insulin sensitivity was assessed by hyperinsulinemic euglycemic clamp, quantitative insulin sensitivity check index, and homeostasis model assessment of insulin resistance; beta-cell function was assessed by calculating the insulinogenic index, homeostasis model assessment, and the disposition index.

Results: Compared with low-NFG subjects, insulin sensitivity and glucose tolerance were lower among persons with isolated IFG and combined IFG-IGT. The hyperinsulinemic euglycemic clamp (micromol/kg x min(-1)/pmol/liter) was 0.109 +/- 0.011 in low-NFG subjects, 0.088 +/- 0.009 in IFG subjects (P = 0.04), and 0.022 +/- 0.003 in IFG-IGT subjects (P = 0.0014). The spread in FPG from 70-125 mg/dl was associated with a greater than 3-fold difference in insulin sensitivity. Compared with low-NFG subjects, the disposition index decreased by 32.8% in high-NFG subjects (P = 0.08), by 45.6% in subjects with isolated IFG (P < 0.02), and by 49.8% (P < 0.02) in those with combined IFG-IGT.

Conclusion: Compared with persons with low-NFG, those with IFG or combined IFG-IGT have significant alteration of glucoregulatory physiology, whereas high-NFG (pre-prediabetes) status might portend nascent glucoregulatory perturbations.