Evidence That Processes Other Than Gluconeogenesis May Influence the Ratio of Deuterium on the Fifth and Third Carbons of Glucose Implications for the Use of 2H2O to Measure Gluconeogenesis in Humans

OBJECTIVE—The deuterated water method uses the ratio of deuterium on carbons 5 and 2 (C5/C2) or 3 and 2 (C3/C2) to estimate the fraction of glucose derived from gluconeogenesis. The current studies determined whether C3 and C5 glucose enrichment is influenced by processes other than gluconeogenesis. RESEARCH DESIGN AND METHODS—Six nondiabetic sub-jects were infused with [3,5-2H2]glucose and insulin while glu-cose was clamped at5 mmol/l; the C5-to-C3 ratio was measured in the in UDP-glucose pool using nuclear magnetic resonance and the acetaminophen glucuronide method. RESULTS—Whereas the C5-to-C3 ratio of the infusate was 1.07, the ratio in UDP-glucose was 1.0 in all subjects both before (0.75 0.07) and during (0.67 0.05) the insulin infusion. CONCLUSIONS—These data indicate that the deuterium on C5 of glucose is lost more rapidly relative to the deuterium on C3