A model-based method for assessing insulin sensitivity from the oral glucose tolerance test

OBJECTIVE - Available insulin sensitivity (IS) methods based on the oral gl ucose 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 OCIS aga inst clamp data. RESEARCH DESIGN AND METHODS - OGIS requires glucose and insulin concentrati ons 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 res ults. For this purpose, 15 lean nondiabetic subjects (BMI < 25 kg/m(2)), 38 obese nondiabetic subjects (BMI > 25 kg/m(2)), and 38 subjects with type 2 diabetes randomly underwent an OTTT and a 120 mU.min(-1).m(-2) insulin inf usion euglycemic clamp Glucose clearance (Cl-CLAMP), calculated as the rati o of glucose infusion to concentration during the last hour of the clamp, w as compared with OGIS. OGIS was also tested On an independent group of 13 s ubjects with impair ed glucose tolerance (IGT). RESULTS - OGIS and Cl-CLAMP 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 diabe tes: R = 0.49; P < 0.02), and in the independent IGT group (R = 0.65, P < 0 .02). Reproducibility of OGIS and Cl-CLAMP were similar (coefficients of va riation. OGIS 7.1%, Cl-CLAMP 6.4%). OGIS was as effective as Cl-CLAMP in di scriminating between groups (for OGIS, lean vs. obese: 440 +/- 10 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 Cl-CLAMP). The relationships betwee n IS and BMI, fasting plasma insulin, and insulin secretion (calculated fro m the OGTT insulin concentration) were examined. OGIS yielded results simil ar to Cl-CLAMP and fully consistent with established physiological principl es. 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. Beca use of its simplicity (only three blood samples required), this method has potential use for clinical investigation including large-scale epidemiologi cal studies.