Comparison of methods for calculating the rate of appearance of exogenous glucose

Abstract

Insulin resistance (IR) is a crucial element of the pathology of the metabolic syndrome, which now affects more than a third of the population in the United States. Understanding the role of hepatic glucose release following a meal in contributing to hyperglycemia is crucial for the assessment of potential new medications. Using an oral glucose tolerance test (OGTT) protocol with two stable isotope tracers, both the rate of appearance of exogenous glucose (Ra_exo) coming from the drink and the suppression of endogenous glucose in response to the drink may be computed. In previous work, investigators have proposed several different methods for computing Ra_exo. The aim of this project was to compare the implementation and results of these methods applied to OGTT data from a cohort of obese adolescent girls. Methods were compared based on inter-method variability and known physiology. Obtaining a reliable estimate of the rate of appearance of exogenous glucose from the drink is necessary to assess hepatic IR. In addition, such an estimate represents a key input to differential equations-based models of whole body glucose-insulin dynamics that are used to quantify hepatic IR, and the method-dependence of the resulting estimates of insulin sensitivity has not been assessed. Improved understanding of interactions between exogenous and endogenous hepatic glucose dynamics will facilitate the characterization of IR in individual patients and different disease conditions and may support the development of targeted therapeutic approaches.