This Article Full Text Full Text (PDF) Supplemental Data Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints, Permissions and Rights Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cali', A. M. G. Articles by Caprio, S. Search for Related Content PubMed PubMed Citation Articles by Cali', A. M. G. Articles by Caprio, S. Related Collections Pediatric Endocrinology Diabetes and Insulin Metabolism

Metabolic Abnormalities Underlying the Different Prediabetic Phenotypes in Obese Adolescents

Department of Pediatrics (A.M.G.C., R.W., S.C.), Yale University School of Medicine, New Haven, Connecticut 06520; and the Department of Biomedical and Surgical Sciences (R.C.B., M.T.), Section of Endocrinology, Universita' di Verona and Azienda Ospedaliera di Verona, 37134 Verona, Italy

Address all correspondence and requests for reprints to: Sonia Caprio, M.D., Yale University School of Medicine, Department of Pediatrics, 330 Cedar Street, P.O. Box 208064, New Haven, Connecticut 06520. E-mail: Sonia.caprio{at}yale.edu.

Objective: The aim of this study was to define the metabolic abnormalities underlying the prediabetic status of isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), and combined IFG/IGT in obese youth.

Research Design and Methods: We used state-of-the-art techniques (hyperinsulinemic-euglycemic and hyperglycemic clamps), applying a model of glucose-stimulated insulin secretion to the glucose and C-peptide concentration, in 40 normal glucose tolerance (NGT), 17 IFG, 23 IGT, and 11 IFG/IGT obese adolescents. Percent fat (by dual-energy x-ray absorptiometry), age, gender and ethnicity were comparable among groups.

Results: Peripheral insulin sensitivity was similar between the IFG and NGT groups. In contrast, the IGT and IFG/IGT groups showed marked reductions in peripheral insulin sensitivity (P < 0.002). Basal hepatic insulin resistance index (basal hepatic glucose production x fasting plasma insulin) was significantly increased in IFG, IGT, and IFG/IGT (P < 0.009) compared with NGT. Glucose sensitivity of first-phase insulin secretion was progressively lower in IFG, IGT, and IFG/IGT compared with NGT. Glucose sensitivity of second-phase secretion showed a statistically significant defect only in the IFG/IGT group. In a multivariate regression analysis, glucose sensitivity of first-phase secretion and basal insulin secretion rate were significant independent predictors of FPG (total r² = 25.9%).

Conclusions: IFG, in obese adolescents, is linked primarily to alterations in glucose sensitivity of first-phase insulin secretion and liver insulin sensitivity. The IGT group is affected by a more severe degree of peripheral insulin resistance and reduction in first-phase secretion. IFG/IGT is hallmarked by a profound insulin resistance and by a new additional defect in second-phase insulin secretion.

This article has been cited by other articles:

				Z. T. Bloomgarden The 6th Annual World Congress on the Insulin Resistance Syndrome Diabetes Care, November 1, 2009; 32(11): e127 - e133. [Full Text] [PDF]

				P. Zeitler Update on Nonautoimmune Diabetes in Children J. Clin. Endocrinol. Metab., July 1, 2009; 94(7): 2215 - 2220. [Abstract] [Full Text] [PDF]

				S. Dagogo-Jack, H. Askari, and G. Tykodi Glucoregulatory Physiology in Subjects with Low-Normal, High-Normal, or Impaired Fasting Glucose J. Clin. Endocrinol. Metab., June 1, 2009; 94(6): 2031 - 2036. [Abstract] [Full Text] [PDF]

				A. M.G. Cali, C. D. Man, C. Cobelli, J. Dziura, A. Seyal, M. Shaw, K. Allen, S. Chen, and S. Caprio Primary Defects in {beta}-Cell Function Further Exacerbated by Worsening of Insulin Resistance Mark the Development of Impaired Glucose Tolerance in Obese Adolescents Diabetes Care, March 1, 2009; 32(3): 456 - 461. [Abstract] [Full Text] [PDF]

				F. Bacha, N. Gungor, S. Lee, and S. A. Arslanian In Vivo Insulin Sensitivity and Secretion in Obese Youth: What are the differences between normal glucose tolerance, impaired glucose tolerance, and type 2 diabetes? Diabetes Care, January 1, 2009; 32(1): 100 - 105. [Abstract] [Full Text] [PDF]

				Z. T. Bloomgarden American College of Endocrinology Pre-Diabetes Consensus Conference: Part One Diabetes Care, October 1, 2008; 31(10): 2062 - 2069. [Full Text] [PDF]