Reproducibility and comparability of insulin sensitivity indices measured by stable-label intravenous glucose tolerance test

We have investigated the reproducibility of (1) insulin sensitivity (S-I*) and glucose effectiveness (S-G*) as measured by the stable-label (one compartment) minimal model, and (2) insulin sensitivity (S-lb*), plasma clearance rate (PCR), basal hepatic output (HGO(b)), and total hepatic glucose output (HGO(0-240)) as measured by the novel stable-label two compartment model of glucose disappearance during labelled intravenous glucose tolerance test (IVGTT) using 6,6-H-2-glucose. Ten normal male subjects were studied on two occasions one week apart. Both models provided estimates of all indices with acceptable precision (CV of parameter estimates less than or equal to 50 %). The within subject CVs of S-1* and S-lb* were comparable (17 % vs 19 %) as were the within subject CVs of S-G* and PCR (13 % vs 16 %). A highly significant linear relationship was observed between S-lb* and S-1* (0.303 +/- 0.046 ml k(-1) min(-1) per mU l(-1) vs 13.04 +/- 1.89 10(-4) min(-1) per mU l(-1), y = 0.0037 x + 0.0002, r = 0.90, p <0.001; mean +/- SE), but not between PCR and S-G* (1.98 +/- 0.15 ml kg(-1) min(-1) vs 0.0089 +/- 0.0005 min(-1), r(s) = 0.34, NS). The two compartment model provided a plausible time-profile of hepatic glucose output during IVGTT, reproducible estimates of HGO(b) (1.96 +/- 0.18 mg kg(-1) min(-1), 15 %; mean +/- SE, within subject CV), and a highly reproducible HGO(0-240) (7 %; within subject CV). We conclude that the stable-label (one compartment) minimal model and the stable-label two compartment model provide reproducible estimates of parameters of glucose kinetics in normal subjects. Insulin sensitivity indices estimated by the two models are strongly linearly related. (C) 1998 by John Wiley & Sons, Ltd.