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 Ͻ 25 kg/m 2 ), 38 obese nondiabetic subjects (BMI Ͼ 25 kg/m 2 ), and 38 subjects with type 2 diabetes randomly underwent an OGTT and a 120 mU ⅐ min Ϫ1 ⅐ m Ϫ2insulin infusion euglycemic clamp. Glucose clearance (Cl CLAMP ), 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 Cl CLAMP were correlated in the whole group (R ϭ 0.77, P Ͻ 0.0001), in the subgroups (lean: R ϭ 0.59; obese: R ϭ 0.73; type 2 diabetes: R ϭ 0.49; P Ͻ 0.02), and in the independent IGT group (R ϭ 0.65, P Ͻ 0.02). Reproducibility of OGIS and Cl CLAMP were similar (coefficients of variation: OGIS 7.1%, Cl CLAMP 6.4%). OGIS was as effective as Cl CLAMP in discriminating between groups (for OGIS, lean vs. obese: 440 Ϯ 16 vs. 362 Ϯ 11 ml ⅐ min Ϫ1⅐ m Ϫ2 , P Ͻ 0.001; lean vs. type 2 diabetes: 440 Ϯ 16 vs. 239 Ϯ 7, P Ͻ 0.0001; obese vs. type 2 diabetes: 362 Ϯ 11 vs. 239 Ϯ 7, P Ͻ 0.0001; results were similar for Cl CLAMP ). 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 Cl CLAMP 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. Diabetes Care 24:539 -548, 2001

Impaired beta cell glucose sensitivity and whole-body insulin sensitivity as predictors of hyperglycaemia in non-diabetic subjects

“…Insulin sensitivity, as an estimate from the OGTT of the glucose clearance during a euglycaemic clamp (expressed in ml per min per square metre of body surface area), was calculated from the plasma glucose and insulin values during the OGTT according to the method of Mari and colleagues [12], which has been validated against the euglycaemic insulin clamp technique. Insulin secretion rates were calculated from plasma C-peptide concentrations by deconvolution, as previously described [18].…”

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“…During recent years, several indices of insulin sensitivity derived from the OGTT have been developed, such as those suggested by Stumvoll and colleagues [20] and by Mari and colleagues [21]. These indices have the advantage of giving information similar to that obtained with the clamp technique [22].…”

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“…Total ISR was computed as the integral over the 3 h of the ISR after the OGTT. Insulin sensitivity was calculated from the OGTT by the oral glucose insulin sensitivity (OGIS), which provides an index that is analogous to the index of insulin sensitivity obtained from the glucose clamp [10].…”