title: Validity of triple- and dual-tracer techniques to estimate glucose appearance.
abstract: The triple-tracer (TT) dilution technique has been proposed to be the gold standard method to measure postprandial glucose appearance. However, validation against an independent standard has been missing. We addressed this issue and also validated the simpler dual-tracer (DT) technique. Sixteen young subjects with type 1 diabetes (age 19.5 ± 3.8 yr, BMI 23.4 ± 1.5 kg/m(2), HbA(1c) 8.7 ± 1.7%, diabetes duration 9.0 ± 6.9 yr, total daily insulin 0.9 ± 0.2 U·kg(-1)·day(-1), mean ± SD) received a variable intravenous 20% dextrose infusion enriched with [U-(13)C]glucose over 8 h to achieve postprandial-resembling glucose excursions while intravenous insulin was administered to achieve postprandial-resembling levels of plasma insulin. Primed [6,6-(2)H(2)]glucose was infused in a manner that mimicked the expected endogenous glucose production and [U-(13)C; 1,2,3,4,5,6,6-(2)H(7)]glucose was infused in a manner that mimicked the expected glucose appearance from a standard meal. Plasma glucose enrichment was measured by gas chromatography-mass spectrometry. The intravenous dextrose infusion served as an independent standard and was reconstructed using the TT and DT techniques with the two-compartment Radziuk/Mari model and an advanced stochastic computational method. The difference between the infused and reconstructed dextrose profile was similar for the two methods (root mean square error 6.6 ± 1.9 vs. 8.0 ± 3.5 μmol·kg(-1)·min(-1), TT vs. DT, P = NS, paired t-test). The TT technique was more accurate in recovering the overall dextrose infusion (100 ± 9 and 92 ± 12%; P = 0.02). The root mean square error associated with the mean dextrose infusion profile was 2.5 and 3.3 μmol·kg(-1)·min(-1) for the TT and DT techniques, respectively. We conclude that the TT and DT techniques combined with the advanced computational method can measure accurately exogenous glucose appearance. The TT technique tends to outperform slightly the DT technique, but the latter benefits from reduced experimental and computational complexity.
authors.affiliation: Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, United Kingdom.
authors.forename: A
authors.initials: A
authors.lastname: Haidar
authors.forename: D
authors.initials: D
authors.lastname: Elleri
authors.forename: J M
authors.initials: JM
authors.lastname: Allen
authors.forename: J
authors.initials: J
authors.lastname: Harris
authors.forename: K
authors.initials: K
authors.lastname: Kumareswaran
authors.forename: M
authors.initials: M
authors.lastname: Nodale
authors.forename: C L
authors.initials: CL
authors.lastname: Acerini
authors.forename: M E
authors.initials: ME
authors.lastname: Wilinska
authors.forename: N
authors.initials: N
authors.lastname: Jackson
authors.forename: A M
authors.initials: AM
authors.lastname: Umpleby
authors.forename: M L
authors.initials: ML
authors.lastname: Evans
authors.forename: D B
authors.initials: DB
authors.lastname: Dunger
authors.forename: R
authors.initials: R
authors.lastname: Hovorka
mesh_terms: D000293:Adolescent; D000465:Algorithms; D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism; D002250:Carbon Radioisotopes / Q000737:chemistry; D003627:Data Interpretation, Statistical; D003903:Deuterium / Q000737:chemistry; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood; D007408:Intestinal Absorption; D007553:Isotope Labeling; D016018:Least-Squares Analysis; D008297:Male; D011849:Radioactive Tracers; D011865:Radioisotope Dilution Technique; D015203:Reproducibility of Results; D013269:Stochastic Processes; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D002250:Carbon Radioisotopes; D003903:Deuterium; D005947:Glucose; D006442:Glycated Hemoglobin; D007328:Insulin; D011849:Radioactive Tracers