Use of a novel triple-tracer approach to assess postprandial glucose metabolism

• Published in: American journal of physiology: endocrinology and metabolism Vol. 284; no. 1; pp. E55 - E69
• Main Authors: Basu, Rita, Di Camillo, Barbara, Toffolo, Gianna, Basu, Ananda, Shah, Pankaj, Vella, Adrian, Rizza, Robert, Cobelli, Claudio
• Format: Journal Article
• Language: English
• Published: United States 01.01.2003
• Subjects: Adult; Blood Glucose - analysis; Blood Glucose - metabolism; Carbon Isotopes; Deuterium; Female; Food; Glucose - administration & dosage; Glucose Tolerance Test - methods; Humans; Infusions, Intravenous; Insulin - blood; Male; Mathematics; Tritium
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00190.2001

1  Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, Minnesota 55905; and 2  Department of Electronics and Informatics, University of Padua, Padua 35131, Italy Numerous studies have used the dual-tracer method to assess postprandial glucose metabolism. The present experiments were undertaken to determine whether the marked tracer nonsteady state that occurs with the dual-tracer approach after food ingestion introduces error when it is used to simultaneously measure both meal glucose appearance (R a meal ) and endogenous glucose production (EGP). To do so, a novel triple-tracer approach was designed: 12 subjects ingested a mixed meal containing [1- 13 C]glucose while [6- 3 H]glucose and [6,6- 2 H 2 ]glucose were infused intravenously in patterns that minimized the change in the plasma ratios of [6- 3 H]glucose to [1- 13 C]glucose and of [6,6- 2 H 2 ]glucose to endogenous glucose, respectively. R a meal and EGP measured with this approach were essentially model independent, since non-steady-state error was minimized by the protocol. Initial splanchnic glucose extraction (ISE) was 12.9% ± 3.4%, and suppression of EGP (EGPS) was 40.3% ± 4.1%. In contrast, when calculated with the dual-tracer one-compartment model, ISE was higher ( P  < 0.05) and EGPS was lower ( P  < 0.005) than observed with the triple-tracer approach. These errors could only be prevented by using time-varying volumes different for R a meal and EGP. Analysis of the dual-tracer data with a two-compartment model reduced but did not totally avoid the problems associated with marked postprandial changes in the tracer-to-tracee ratios. We conclude that results from previous studies that have used the dual-tracer one-compartment model to measure postprandial carbohydrate metabolism need to be reevaluated and that the triple-tracer technique may provide a useful approach for doing so. glucose kinetics; initial splanchnic glucose uptake; nonsteady state