Assessment of postprandial glucose metabolism: conventional dual- vs. triple-tracer method

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-(13)C]glucose to trace ingested glucose and [6,6-(2)H(2)]glucose constantly infused. A third tracer, [6-(3)H]glucose, was infused at variable rates to render the calculation of R(a meal) and EGP virtually model independent. The dual-tracer method analyzed with a one-compartment model performed poorly, since R(a 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 micromol/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 micromol/kg, P = 0.0117) and EGP still showed a paradoxical behavior. R(d), estimated from R(a 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 R(a meal), EGP, and R(d).