β-Cell Function Across the Spectrum of Glucose Tolerance in Obese Youth

β-Cell Function Across the Spectrum of Glucose Tolerance in Obese Youth Ram Weiss 1 , Sonia Caprio 1 , Maddalena Trombetta 2 , Sara E. Taksali 1 , William V. Tamborlane 1 3 and Riccardo Bonadonna 2 1 Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut 2 Department of Biomedical & Surgical Sciences, Section of Endocrinology & Metabolic Diseases, University of Verona and Azienda Ospedaliera di Verona, Verona, Italy 3 General Clinical Research Center of the Yale University School of Medicine, New Haven, Connecticut Address correspondence and reprint requests to Dr. Ram Weiss, Department of Pediatrics, Yale University School of Medicine, 333 Cedar St., P.O. Box 208064, New Haven, CT, 06520. E-mail: ram.weiss{at}yale.edu Abstract The profile of insulin secretion and the role of proinsulin processing across the spectrum of glucose tolerance in obese youth have not been studied. The aims of this study were to define the role of insulin secretion and proinsulin processing in glucose regulation in obese youth. We performed hyperglycemic clamps to assess insulin secretion, applying a model of glucose-stimulated insulin secretion to the glucose and C-peptide concentration data. Thirty obese youth with normal glucose tolerance (NGT), 22 with impaired glucose tolerance (IGT), and 10 with type 2 diabetes were studied. The three groups had comparable anthropometric measures and insulin sensitivity. The glucose sensitivity of first-phase secretion showed a significant stepwise decline from NGT to IGT and from IGT to type 2 diabetes. The glucose sensitivity of second-phase secretion was similar in NGT and IGT subjects yet was significantly lower in subjects with type 2 diabetes. Proinsulin-to-insulin ratios were comparable during first- and second-phase secretion between subjects with NGT and IGT and were significantly increased in type 2 diabetes. Obese youth with IGT have a significant defect in first-phase insulin secretion, while a defect in second-phase secretion and proinsulin processing is specific for type 2 diabetes in this age-group. IGT, impaired glucose tolerance NGT, normal glucose tolerance OGTT, oral glucose tolerance test Footnotes The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Accepted March 14, 2005. Received November 29, 2004. DIABETES