A Model-Based Method for Assessing Insulin Sensitivity From the Oral Glucose Tolerance Test

Abstract

OBJECTIVE—Available insulin sensitivity (IS) methods based on the oral glucose tolerance test (OGTT) are empirical. We used a glucose-insulin model to derive an OGTT-based IS (oral glucose insulin sensitivity [OGIS]) index, which predicts glucose clearance in a glucose clamp. We validated OGIS against clamp data. RESEARCH DESIGN AND METHODS—OGIS requires glucose and insulin concentrations from a 75-g OGTT at 0, 2, and 3 h (3-h OGTT) or at 0, 1.5, and 2 h (2-h OGTT). The formula includes six constants optimized to match the clamp results. For this purpose, 15 lean nondiabetic subjects (BMI < 25 kg/m2), 38 obese nondiabetic subjects (BMI > 25 kg/m2), and 38 subjects with type 2 diabetes randomly underwent an OGTT and a 120 mU · min−1 · m−2 insulin infusion euglycemic clamp. Glucose clearance (ClCLAMP), calculated as the ratio of glucose infusion to concentration during the last hour of the clamp, was compared with OGIS. OGIS was also tested on an independent group of 13 subjects with impaired glucose tolerance (IGT). RESULTS—OGIS and ClCLAMP were correlated in the whole group (R = 0.77, P < 0.0001), in the subgroups (lean: R = 0.59; obese: R = 0.73; type 2 diabetes: R = 0.49; P < 0.02), and in the independent IGT group (R = 0.65, P < 0.02). Reproducibility of OGIS and ClCLAMP were similar (coefficients of variation: OGIS 7.1%, ClCLAMP 6.4%). OGIS was as effective as ClCLAMP in discriminating between groups (for OGIS, lean vs. obese: 440 ± 16 vs. 362 ± 11 ml · min−1 · m−2, P < 0.001; lean vs. type 2 diabetes: 440 ± 16 vs. 239 ± 7, P < 0.0001; obese vs. type 2 diabetes: 362 ± 11 vs. 239 ± 7, P < 0.0001; results were similar for ClCLAMP). The relationships between IS and BMI, fasting plasma insulin, and insulin secretion (calculated from the OGTT insulin concentration) were examined. OGIS yielded results similar to ClCLAMP and fully consistent with established physiological principles. The performance of the index for the 3-h and 2-h OGTT was similar. CONCLUSIONS—OGIS is an index of IS in good agreement with the clamp. Because of its simplicity (only three blood samples required), this method has potential use for clinical investigation including large-scale epidemiological studies.