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Validation of Insulin Sensitivity Indices from Oral Glucose Tolerance Test Parameters in Obese Children and Adolescents

Department of Pediatrics (C.W.Y., R.W., S.E.T., T.S.B., W.V.T., S.C.), and Children’s and Adult General Clinical Research Centers (J.D.); and Howard Hughes Medical Institute (S.D.), Yale University School of Medicine, New Haven, Connecticut 06520

Address all correspondence and requests for reprints to: Dr. Sonia Caprio, Department of Pediatrics, Yale University School of Medicine, P.O. Box 802064, New Haven, Connecticut 06520. E-mail: sonia.caprio{at}yale.edu.

Given the extreme increase in prediabetes, type 2 diabetes, and the potential for metabolic syndrome in obese youth, identifying simplified indexes for assessing stimulated insulin sensitivity is critical. The purpose of this study was validation of two surrogate indexes of insulin sensitivity determined from the oral glucose tolerance test (OGTT): the composite whole body insulin sensitivity index (WBISI) and the insulin sensitivity index (ISI). An obese population (aged 8–18 yr) of normal and impaired glucose tolerance individuals was studied. One group (n = 38) performed both the euglycemic-hyperinsulinemic clamp and OGTT for comparison of insulin sensitivity measurements as well as ¹H-magnetic resonance spectroscopy estimates of intramyocellular lipid content. Another larger (n = 368) cohort participated only in an OGTT. Both the WBISI and ISI represented good estimates (r = 0.78 and 0.74; P < 0.0005) for clamp-derived insulin sensitivity (glucose disposed, M-value), respectively. In the large cohort, the surrogate indexes demonstrated the shift toward poorer function and increased risk profile as a function of insulin resistance. Additionally, the WBISI and ISI correlated with intramyocellular lipid content (r = -0.74 and -0.71; P < 0.0001), a tissue marker for insulin resistance. Insulin sensitivity can be estimated using plasma glucose and insulin responses derived from the OGTT in obese youth with normal and impaired glucose tolerance.

This work was supported by NIH Grants RO1-HD-40787 and RO1-HD-28016 (to S.C.), the Stephen I. Morse Pediatric Diabetes Research Fund (to R.W.), the Jeanne B. Kempner Scholar Award (to C.W.Y.), and Award K24-HD-01464 for Patient-Oriented Research (to S.C.) and in part by Yale Children’s Clinical Research Center Grant MO1-RR-00125 and General Clinical Research Center Grant MO1-RR-06022, General Clinical Research Centers Program, National Center for Research Resources, NIH.

Abbreviations: BMI, Body mass index; HDL, high-density lipoprotein; ¹H-MRS, ¹H-MR spectroscopy; HOMA-IR, homeostasis model assessment-insulin resistance; IGI, insulinogenic index; IGT, impaired glucose tolerance; IMCL, intramyocellular lipid content; ISI, insulin sensitivity index; MR, magnetic resonance; NGT, normal glucose tolerance; OGTT, oral glucose tolerance test; WBISI, whole body insulin sensitivity index.

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