Surrogate Estimates of Insulin Sensitivity in Obese Youth along the Spectrum of Glucose Tolerance from Normal to Prediabetes to Diabetes

Context: In epidemiological studies of childhood obesity, simple and reliable surrogate estimates of insulin sensitivity are needed because the gold standard, the hyperinsulinemic-euglycemic clamp, is not feasible on a large scale. Objective: To examine the correlation of fasting and oral glucose tolerance test (OGTT)-derived surrogate indices of insulin sensitivity with the hyperinsulinemic-euglycemic clamp in obese adolescents with normal glucose tolerance, prediabetes, and diabetes. Patients and Design: A total of 188 overweight/obese adolescents (10 to <20 yr old) who completed a standard 2-h OGTT and 3-h hyperinsulinemic-euglycemic clamp were included. Fasting-derived surrogates [fasting glucose (G(F)), fasting insulin (I-F), 1/I-F, G(F)/I-F, homeostasis model assessment and quantitative insulin sensitivity check index] and OGTT-derived surrogates [whole-body insulin sensitivity index and the ratio of glucose and insulin areas under the curve (Gluc(AUC)/Ins(AUC))] were calculated. Main Outcome Measures: We evaluated the correlations between the clamp-measured insulin sensitivity and the surrogate estimates and area under the receiver operating characteristic curves. Results: Fasting indices (1/I-F, G(F)/I-F, homeostasis model assessment of insulin sensitivity, and quantitative insulin sensitivity check index) correlated significantly with clamp insulin sensitivity (r = 0.82, 0.78, 0.81, and 0.80, respectively), with lower correlations between the OGTT surrogates and clamp (whole-body insulin sensitivity index, r = 0.77; Gluc(AUC)/Ins(AUC), r = 0.62). The area under the receiver operating characteristic curves was more than or equal to 0.94 for all surrogates except Gluc(AUC)/Ins(AUC). Across quartiles of clamp-measured insulin sensitivity, there was a significant overlap in individual values of I-F, 1/I-F, and G(F)/I-F. Conclusion: In obese adolescents with normal or impaired glucose tolerance or diabetes, OGTT-derived surrogates do not offer any advantage over the simpler fasting indices, which correlate strongly with clamp insulin sensitivity. Surrogate indices of insulin sensitivity could be used in epidemiological studies but not to define insulin resistance in individual patients or research subjects. (J Clin Endocrinol Metab 96: 2136-2145, 2011)