Stable-Label Intravenous Glucose Tolerance Test Minimal Model

Abstract

The minimal model approach to estimating insulin sensitivity (S_I) and glucose effectiveness in promoting its own disposition at basal insulin (S_G) is a powerful tool that has been underutilized given its potential applications. In part, this has been due to its inability to separate insulin and glucose effects on peripheral uptake from their effects on hepatic glucose inflow. Prior enhancements, with radiotracer labeling of the dosage, permit this separation but are unsuitable for use in pregnancy and childhood. In this study, we labeled the intravenous glucose tolerance test (IVGTT) dosage with [6,6-²H₂]glucose, [2-²H]glucose, or both stable isotopically labeled glucose tracers and modeled glucose kinetics in six postabsorptive, nonobese adults. As previously found with the radiotracer model, the tracer-estimated derived from the stable-label IVGTT was greater than S_I in each case except one, and the tracer-estimated was less than S_G in each instance. More importantly, however, the stable-label IVGTT estimated each parameter with an average precision of ± 5% (range 3–9%) compared to average precisions of ±74% (range 7–309%) for S_Gand ±22% (range 3–72%) for S_I. In addition, because of the different metabolic fates of the two deuterated tracers, there were minor differences in basal insulin-derived measures of glucose effectiveness, but these differences were negligible for parameters describing insulin-stimulated processes. In conclusion, the stable-label IVGTT is a simple, highly precise means of assessing insulin sensitivity and glucose effectiveness at basal insulin that can be used to measure these parameters in individuals of all ages, including children and pregnant women.