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

Abstract

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 glucose allostasis can be demonstrated using oral glucose tolerance tests (OGTTs) and the effects of the dynamics of beta-cell demand on longitudinal changes of glucose tolerance in obese youth. 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 beta-cell demand and the degree of obesity on glucose tolerance. Glucose allostasis can be demonstrated using indexes derived from an OGTT. 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 follow-up was not. 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.