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Published online May 2, 2007
Diabetes Care 30:1845-1850, 2007
DOI: 10.2337/dc07-0325
© 2007 by the American Diabetes Association
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Cardiovascular and Metabolic Risk
Original Article

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

Ram Weiss, MD, PHD1,2, Anna M. Cali, MD1, James Dziura, PHD3, Tania S. Burgert, MD1, William V. Tamborlane, MD1 and Sonia Caprio, MD1

1 Department of Pediatric Endocrinology, Yale University School of Medicine, New Haven, Connecticut
2 Department of Pediatrics and the Diabetes Center, Hadassah, Hebrew University School of Medicine, Jerusalem, Israel
3 General Clinical Research Center, Yale University School of Medicine, New Haven, Connecticut

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

OBJECTIVE— One of the signals for the ß-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 ß-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 ß-cell demand and the degree of obesity on glucose tolerance.

RESULTS— Glucose allostasis can be demonstrated using indexes derived from an OGTT. Increasing ß-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 ß-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 ß-cell enhancement alongside a significant reduction in obesity may be needed to prevent the development of altered glucose metabolism in obese youth.

Abbreviations: BCDI, ß-cell demand index • DI, disposition index • IGI, insulinogenic index • OGTT, oral glucose tolerance test • WBISI, whole-body insulin sensitivity index


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