Degree of Obesity and Glucose Allostasis Are Major Effectors of Glucose Tolerance Dynamics in Obese Youth

  1. Ram Weiss, MD, PHD12,
  2. Anna M. Cali, MD1,
  3. James Dziura, PHD3,
  4. Tania S. Burgert, MD1,
  5. William V. Tamborlane, MD1 and
  6. Sonia Caprio, MD1
  1. 1Department of Pediatric Endocrinology, Yale University School of Medicine, New Haven, Connecticut
  2. 2Department of Pediatrics and the Diabetes Center, Hadassah, Hebrew University School of Medicine, Jerusalem, Israel
  3. 3General Clinical Research Center, Yale University School of Medicine, New Haven, Connecticut
  1. Address correspondence and reprint requests to Dr. Ram Weiss, Diabetes Center, Hadassah—Hebrew University School of Medicine, P.O. Box 12000, Ein Kerem, Jerusalem 91120. E-mail: weissr{at}hadassah.org.il

Abstract

OBJECTIVE— One of the signals for the β-cell to maintain an adequate response to worsening insulin sensitivity is elevated ambient glycemia, namely the concept of “glucose allostasis.” We examined whether glucose allostasis can be demonstrated using oral glucose tolerance tests (OGTTs) and the effects of the dynamics of β-cell demand on longitudinal changes of glucose tolerance in obese youth.

RESEARCH DESIGN AND METHODS— A cross-sectional analysis of 784 OGTTs of obese youth was used to demonstrate the concept of allostasis, and a longitudinal assessment of 181 subjects was used to examine the effects of changes in β-cell demand and the degree of obesity on glucose tolerance.

RESULTS— Glucose allostasis can be demonstrated using indexes derived from an OGTT. Increasing β-cell demand and the degree of obesity at baseline were independently related to elevations in ambient glycemia over time. Baseline BMI Z score was a significant contributor to elevated glucose levels on the second OGTT, while the change in degree of obesity during follow-up was not.

CONCLUSIONS— Increasing β-cell demand related to worsening insulin sensitivity and the degree of obesity per se have independent roles in the development of elevated glucose levels over time. This implicates that peripheral insulin sensitization and/or β-cell enhancement alongside a significant reduction in obesity may be needed to prevent the development of altered glucose metabolism in obese youth.

Footnotes

  • Published ahead of print at http://care.diabetesjournals.org on 2 May 2007. DOI: 10.2337/dc07-0325.

    Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/dc07-0325.

    A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

    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 April 18, 2007.
    • Received February 18, 2007.
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  1. Published online before print May 2, 2007, doi: 10.2337/dc07-0325 Diabetes Care July 2007 vol. 30 no. 7 1845-1850
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