The quantification of gluconeogenesis in healthy men by (H2O)-H-2 and [2-C-13]glycerol yields different results: Rates of gluconeogenesis in healthy men measured with (H2O)-H-2 are higher than those measured with [2-C-13]glycerol

The quantification of gluconeogenesis (GNG) by (H2O)-H-2 and [2-C-13]glycer ol and the mass isotopomer dilution analysis of glucose does not involve as sumptions regarding the enrichment of the oxaloacetate precursor pool. To c ompare these two methods we measured GNG in six healthy postabsorptive male s under identical, strictly standardized, eucaloric conditions, once after oral administration of (H2O)-H-2 and once during a primed continuous infusi on of [2-C-13]glycerol. Endogenous glucose production (EGP) was measured by infusion of [6,6-H-2(2)]glucose. EGP was not different after (H2O)-H-2 adm inistration or during [2-C-13]glycerol infusion (12.2 +/- 0.7 us. 11.7 +/- 0.3 mu mol/kg min). However, GNG measured after (H2O)-H-2 administration wa s significantly higher than that during [2-13C]glycerol infusion (7.4 +/- 0 .7 us. 4.9 +/- 0.6 mu mol/kg min; P = 0.03), representing approximately 60% and 41% of EGP, respectively. The (H2O)-H-2 study was repeated during prim ed continuous infusion of unlabeled glycerol, showing that infusion of glyc erol at the rate used in the [2-C-13]-glycerol method does not affect the m easurement of GNG with (H2O)-H-2, uiz. 7.4 +/- 0.7 without glycerol vs. 7.6 +/- 0.9 mu mol/kg.min with glycerol, representing approximately 60% us. 62 % of EGP. In conclusion, GNG measured by (H2O)-H-2 yields higher results th an those measured by [2-C-13]glycerol. This discrepancy is not merely cause d by infusion of glycerol per se. Rather, the discrepancy between both meth ods probably relates to conceptual problems in underlying assumptions in on e or both methods.