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

• Published in: American journal of physiology: endocrinology and metabolism Vol. 291; no. 4; pp. E800 - E806
• Main Authors: Toffolo, Gianna, Basu, Rita, Dalla Man, Chiara, Rizza, Robert, Cobelli, Claudio
• Format: Journal Article
• Language: English
• Published: United States 01.10.2006
• Subjects: Adult; Blood Glucose - metabolism; Carbon Isotopes - blood; Carbon Isotopes - metabolism; Deuterium - blood; Deuterium - metabolism; Eating - physiology; Female; Glucose - administration & dosage; Glucose - metabolism; Humans; Insulin - blood; Kinetics; Male; Models, Biological; Postprandial Period - physiology; Tritium - blood; Tritium - metabolism
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00461.2005

1 Department of Information Engineering, University of Padua, Padua, Italy; and 2 Department of Internal Medicine, Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic and Foundation, Rochester, Minnesota Submitted 21 September 2005 ; accepted in final form 17 May 2006 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 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. 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 . nonsteady state; turnover; meal; kinetics; compartmental models Address for reprint requests and other correspondence: Claudio Cobelli, Dept. of Information Engineering, Via Gradenigo 6/a, 35131 Padua, Italy (e-mail: cobelli{at}dei.unipd.it )