The Quantification of Gluconeogenesis in Healthy Men by ²H₂O and[ 2-¹³C]Glycerol Yields Different Results: Rates of Gluconeogenesis in Healthy Men Measured with ²H₂O Are Higher Than Those Measured with [2-¹³C]Glycerol

The quantification of gluconeogenesis (GNG) by ²H₂O and [2-¹³C]glycerol and the mass isotopomer dilution analysis of glucose does not involve assumptions regarding the enrichment of the oxaloacetate precursor pool. To compare these two methods we measured GNG in six healthy postabsorptive males under identical, strictly standardized, eucaloric conditions, once after oral administration of ²H₂O and once during a primed continuous infusion of [2-¹³C]glycerol. Endogenous glucose production (EGP) was measured by infusion of[ 6,6-²H₂]glucose. EGP was not different after ²H₂O administration or during[ 2-¹³C]glycerol infusion (12.2 ± 0.7 vs. 11.7 ± 0.3 μmol/kg·min). However, GNG measured after ²H₂O administration was significantly higher than that during [2-¹³C]glycerol infusion (7.4 ± 0.7 vs. 4.9 ± 0.6μ mol/kg·min; P = 0.03), representing approximately 60% and 41% of EGP, respectively. The ²H₂O study was repeated during primed continuous infusion of unlabeled glycerol, showing that infusion of glycerol at the rate used in the [2-¹³C]glycerol method does not affect the measurement of GNG with ²H₂O, viz. 7.4 ± 0.7 without glycerol vs. 7.6 ± 0.9 μmol/kg·min with glycerol, representing approximately 60% vs. 62% of EGP. In conclusion, GNG measured by ²H₂O yields higher results than those measured by[ 2-¹³C]glycerol. This discrepancy is not merely caused by infusion of glycerol per se. Rather, the discrepancy between both methods probably relates to conceptual problems in underlying assumptions in one or both methods.