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Degree of obesity and glucose allostasis are major effectors of glucose tolerance dynamics in obese youth

Pediatrics¹
General Clinical Research Center²
Yale University School of Medicine, Pediatrics Hadassah - Hebrew University School of Medicine, Jerusalem, Israel³

weissr{at}hadassah.org.il

ABSTRACT

Objective:One of the signals for the beta cell to maintain an adequate response to worsening insulin sensitivity is elevated ambient glycemia, namely the concept of "glucose allostasis". We examined whether the "glucose allostasis" can be demonstrated using oral glucose tolerance tests and the effects of the dynamics of beta cell demand on longitudinal changes of glucose tolerance in obese youth.

Design and methods:A cross sectional analysis of 784 oral glucose tolerance tests 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 beta cell demand and degree of obesity on glucose tolerance.

Results:"Glucose allostasis" can be demonstrated using indices derived from an oral glucose tolerance test. Increasing beta 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 the follow up was not.

Conclusions:Increasing beta 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 beta cell enhancement alongside a significant reduction in obesity may be needed to prevent the development of altered glucose metabolism in obese youth.

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