TY - JOUR
T1 - Assessment of postprandial glucose metabolism
T2 - Conventional dual- vs. triple-tracer method
AU - Toffolo, Gianna
AU - Basu, Rita
AU - Dalla Man, Chiara
AU - Rizza, Robert
AU - Cobelli, Claudio
PY - 2006
Y1 - 2006
N2 - The dual-tracer method has been used conventionally for assessment of postprandial fluxes, i.e., appearance in plasma of ingested glucose (R a meal), endogenous glucose production (EGP), and disposal (R d). To quantify the magnitude of errors affecting the calculations and their dependence on model assumptions, this method was assessed and compared with the triple-tracer method, which provides model-independent estimates. For this purpose, the dual-tracer protocol was performed twice in eight normal subjects, with [1-13C]glucose to trace ingested glucose and [6,6-2H2]glucose constantly infused. A third tracer, [6-3H]glucose, was infused at variable rates to render the calculation of Ra meal and EGP virtually model independent. The dual-tracer method analyzed with a one-compartment model performed poorly, since Ra meal peak was significantly lower and delayed compared with triple-tracer reference, resulting in a significantly lower estimation of the amount of absorbed glucose (9,036 ± 558 vs. 11,316 ± 823 μmol/kg, P = 0.0117). EGP showed a paradoxical pattern, with an initial overshoot followed by a rapid decay to negative values, resulting in a significant underestimation of EGP suppression (57 ± 3 vs. 65 ± 4%, P = 0.0117). A two-compartment model performed better but did not overcome the limitations of the dual-tracer approach, since the amount of absorbed glucose was still significantly underestimated (10,231 ± 661 vs. 12,169 ± 838 μmol/kg, P = 0.0117) and EGP still showed a paradoxical behavior. Rd, estimated from Ra meal and EGP, was significantly underestimated with the dual-tracer method, irrespective of adopted model. We conclude that three suitably infused tracers are required for accurate assessment of postprandial Ra meal, EGP, and Rd.
AB - The dual-tracer method has been used conventionally for assessment of postprandial fluxes, i.e., appearance in plasma of ingested glucose (R a meal), endogenous glucose production (EGP), and disposal (R d). To quantify the magnitude of errors affecting the calculations and their dependence on model assumptions, this method was assessed and compared with the triple-tracer method, which provides model-independent estimates. For this purpose, the dual-tracer protocol was performed twice in eight normal subjects, with [1-13C]glucose to trace ingested glucose and [6,6-2H2]glucose constantly infused. A third tracer, [6-3H]glucose, was infused at variable rates to render the calculation of Ra meal and EGP virtually model independent. The dual-tracer method analyzed with a one-compartment model performed poorly, since Ra meal peak was significantly lower and delayed compared with triple-tracer reference, resulting in a significantly lower estimation of the amount of absorbed glucose (9,036 ± 558 vs. 11,316 ± 823 μmol/kg, P = 0.0117). EGP showed a paradoxical pattern, with an initial overshoot followed by a rapid decay to negative values, resulting in a significant underestimation of EGP suppression (57 ± 3 vs. 65 ± 4%, P = 0.0117). A two-compartment model performed better but did not overcome the limitations of the dual-tracer approach, since the amount of absorbed glucose was still significantly underestimated (10,231 ± 661 vs. 12,169 ± 838 μmol/kg, P = 0.0117) and EGP still showed a paradoxical behavior. Rd, estimated from Ra meal and EGP, was significantly underestimated with the dual-tracer method, irrespective of adopted model. We conclude that three suitably infused tracers are required for accurate assessment of postprandial Ra meal, EGP, and Rd.
KW - Compartmental models
KW - Kinetics
KW - Meal
KW - Nonsteady state
KW - Turnover
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U2 - 10.1152/ajpendo.00461.2005
DO - 10.1152/ajpendo.00461.2005
M3 - Article
C2 - 16720627
AN - SCOPUS:33749259584
SN - 0193-1849
VL - 291
SP - E800-E806
JO - American Journal of Physiology - Endocrinology and Metabolism
JF - American Journal of Physiology - Endocrinology and Metabolism
IS - 4
ER -