A stable isotope minimal model protocol with oral glucose administration.

A protocol for investigating glucose metabolism whereby stable isotope tracer is given intravenously after an oral glucose challenge is described. Frequent sampling of plasma glucose and insulin allows the tracer disappearance to be interpreted on the basis of established minimal models. We have investigated the glucose effectiveness and insulin sensitivity parameters and their reproducibility in a group of six healthy adults, each studied twice. A mono-compartmental description of glucose distribution did not provide a physiological description of glucose kinetics, whereas a two-compartment model gave adequate results in every case. The estimates of glucose effectiveness and insulin sensitivity were 2-3 times higher than those obtained in similar populations using the conventional protocol of the frequently sampled intravenous glucose tolerance test, and this appeared to be related to the kinetics of transport of glucose from accessible to remote pools. The indices of insulin sensitivity obtained in this way were highly reproducible, with a between-test correlation of 93%.