EFFECTS OF INSULIN ON GLUCOSE-TURNOVER RATES IN-VIVO - ISOTOPE-DILUTION VERSUS CONSTANT SPECIFIC ACTIVITY TECHNIQUE

The conventional isotope dilution technique was compared with the more accurate constant specific activity (SA) method at six different insu lin levels. Paired euglycemic clamp studies were performed in 30 norma l subjects (4-hour insulin infusion: 5, 10, 20, 40, 80, and 160 mU . m (-2). min(-1)) using primed-constant 3-H-3-glucose infusion and either conventional unlabeled glucose infusates (Cold-GINF) or labeled gluco se infusates (Hot-GINF) to maintain constant SA. At all insulin levels , both glucose disappearance (R(d)) and hepatic glucose production (HG P) were underestimated by the conventional technique, and errors durin g the first 2 hours correlated with glucose infusion rates (GIRs) (r = .93, P <.00001). During the second hour, mean underestimation of HGP v aried from 20% +/- 9% to 84% +/- 16% of basal rates from low-dose to h igh-dose insulin infusion studies. During prolonged equilibration (3 t o 4 hours), errors decreased but were still significant in the two low -dose insulin infusion protocols during the fourth hour. In conclusion , using the conventional isotope dilution technique, suppression of gl ucose production was overestimated and stimulation of glucose R(d) was underestimated, and these errors were greater the higher the GIR. Thu s, artifactually greater hepatic and smaller peripheral effects may ha ve been assumed for factors or therapies that influence insulin sensit ivity in previous studies using a conventional isotope dilution techni que, and therefore, reevaluation of these issues may be relevant in fu ture studies. Copyright (C) 1996 by W.B. Saunders Company