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1 Department of Information Engineering, University of Padova, Padova, Italy
2 Department of Internal Medicine Division of Endocrinology, Diabetes, Metabolism & Nutrition, Mayo Clinic and Foundation, Rochester, Minnesota, United States
* To whom correspondence should be addressed. E-mail: cobelli{at}dei.unipd.it.
The dual tracer method conventionally has been used for assessment of postprandial fluxes, i.e. appearance in plasma of ingested glucose (Rameal), glucose production (EGP) and disposal (Rd). To quantify the magnitude of errors affecting the calculations and their dependence on model assumptions, this method was assessed in comparison with the triple tracer method, which provides model-independent estimates. To this purpose, the dual tracer protocol was performed twice in 8 normals, 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 Rameal and EGP virtually model-independent. The dual tracer method analysed with a one-compartment model performed poorly, since Rameal peak was significantly lower and delayed compared to triple tracer reference, resulting in a significantly lower estimation of the amount of absorbed glucose (9036±558 vs 11316±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 amount of absorbed glucose was still significantly underestimated (10231±661 vs 12169±838 µmol/kg, p=0.0117) and EGP still showed a paradoxical behaviour. Rd, estimated from Rameal and EGP, was significantly underestimated with the dual tracer method, irrespectively of adopted model. We conclude that three suitably infused tracers are required for accurate assessment of postprandial Rameal, EGP and, thus, of Rd.
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