Diabetes, Vol 38, Issue 6 744-751, Copyright © 1989 by American Diabetes Association
Mechanism for underestimation of isotopically determined glucose disposal
H Yki-Jarvinen, A Consoli, N Nurjhan, AA Young and JE Gerich
Clinical Diabetes and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, Arizona.
Use of [3H]glucose and a one-compartment model to determine glucose
kinetics frequently underestimates the rate of glucose production (Ra). To
assess to what extent an isotope effect, a tracer contaminant, or
inadequacy of the model was responsible, we measured glucose Ra and forearm
clearance of tracer and unlabeled glucose at various concentrations of
plasma insulin (approximately 50, approximately 160, and approximately 1800
microU/ml) and plasma glucose (approximately 90, approximately 160,
approximately 250, and approximately 400 mg/dl) under steady-state and
non-steady-state conditions. Under isotopic steady-state conditions, the
clearances of tracer and unlabeled glucose across the forearm were
identical, and exogenous glucose infusion rates did not differ
significantly from the isotopically determined glucose Ra (10.0 +/- 1.3 vs.
10.5 +/- 1.0 mg.kg-1 fat-free mass.min-1, respectively). However, under
isotopic non-steady-state conditions, the isotopically determined Ra was
significantly lower than the glucose infusion rate (11.5 +/- 1.3 vs. 13.7
+/- 1.5 mg.kg-1 fat-free mass.min-1, respectively, P less than .001), and
the underestimation was related to the deviation from the isotopic steady
state. When [3H]glucose specific activity of plasma samples from
experiments with the greatest underestimation of Ra was determined by
high-performance liquid chromatography, less than 7% of the underestimation
could be accounted for by a contaminant. These results indicate that
inadequacy of the one-compartment model is responsible for underestimation
of glucose Ra under non-steady-state conditions and that there is no
detectable isotopic effect or appreciable contaminant of [3-3H]glucose. We
conclude that under isotopic steady-state conditions, [3-3H]glucose is a
reliable tracer for glucose kinetic studies in humans.