title: Use of a novel triple-tracer approach to assess postprandial glucose metabolism.
abstract: 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.
authors.affiliation: Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
authors.forename: Rita
authors.initials: R
authors.lastname: Basu
authors.forename: Barbara
authors.initials: B
authors.lastname: Di Camillo
authors.forename: Gianna
authors.initials: G
authors.lastname: Toffolo
authors.forename: Ananda
authors.initials: A
authors.lastname: Basu
authors.forename: Pankaj
authors.initials: P
authors.lastname: Shah
authors.forename: Adrian
authors.initials: A
authors.lastname: Vella
authors.forename: Robert
authors.initials: R
authors.lastname: Rizza
authors.forename: Claudio
authors.initials: C
authors.lastname: Cobelli
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis / Q000378:metabolism*; D002247:Carbon Isotopes; D003903:Deuterium; D005260:Female; D005502:Food; D005947:Glucose / Q000008:administration & dosage; D005951:Glucose Tolerance Test / Q000379:methods*; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood; D008297:Male; D008433:Mathematics; D014316:Tritium
chemical_list: D001786:Blood Glucose; D002247:Carbon Isotopes; D007328:Insulin; D014316:Tritium; D003903:Deuterium; D005947:Glucose