Submitted to: Diabetes
Publication Type: Peer reviewed journal
Publication Acceptance Date: 8/1/2002
Publication Date: 11/1/2002
Citation: Tigas SK, Sunehag AL, Haymond MW. Impact of Duration of Infustion and Choice of Isotope Label on Isotope Recycling in Glucose Homeostasis. 2002 Diabetes 51:3170-3175. Interpretive Summary: These studies unequivocally demonstrate the importance of the duration of isotope infusion in achieving valid results. Thus, investigators carrying out studies on glucose turnover rates using tracer infusion periods of less than 4 - 5 h, should be cognizant that their measurements of glucose Ra using steady state equations may be overestimated, which has to be taken into account when drawing conclusions from their data.
Technical Abstract: The purposes of this study were to quantitate the impact of the duration of infusion and choice of stable isotope of glucose on measures of glucose rate of appearance (glucose Ra) and to determine whether the differences observed were due to tracer recycling via the glycogen pool (direct pathway) or gluconeogenesis (indirect pathway). Six healthy adult volunteers were studied on 4 occasions in the postabsorptive state during infusions of [1-13C]- and [6,6-2H2]glucose: (A) 2.5 h infusion of both, (B) and (C) 2.5 h infusion of one and 14.5 h infusion of the other isotope and (D) 5 h infusion of [6,6-2H2]glucose and 2.5 h infusion of [1-13C]glucose. Infusion of both isotopes for 2.5 h resulted in similar glucose Ra values. When compared to a 14.5 h infusion, the 2.5 h glucose tracer infusion overestimated glucose Ra by 26-35%. Glucose 13C recycled via the Cori cycle, resulting in slower decay from the plasma pool and longer half-life (t1/2) of [1-13C]glucose compared to [6,6-2H2]glucose. There was no detectable release of [13C]- or [2H2]glucose tracer into the plasma pool following administration of glucagon. These data demonstrate that glucose Ra varies not as a result of isotope cycling but as a result of differences in duration of isotope infusion regardless of the isotope employed. This is most likely due to incomplete isotope and substrate equilibration with the 2.5 h infusion. The potential error was reduced by nearly 80% using a 5 h infusion of [6,6-2H2]glucose. These studies demonstrate that the duration of isotope infusion has significantly greater impact on quantitation of glucose Ra than does the selection of isotope.