title: Calculating glucose fluxes during meal tolerance test: a new computational approach.
abstract: A new calculation method is proposed to quantify the endogenous glucose production (EGP), the glucose appearance rate due to meal ingestion (R(a meal)), and the glucose disposal (R(d)) during a three-tracer study design. The method utilizes the maximum likelihood theory combined with a regularization method to achieve a theoretically coherent computational framework. The method uses the two-compartment formulation of the glucose kinetics. Instead of assuming smoothness of unlabeled and labeled glucose concentrations, the method assumes that the EGP, the R(a meal), and the fractional glucose clearance are smooth, increasing plausibility of their individual estimates. The method avoids transformation of the measurement errors, which may skew the estimates of the EGP, R(a meal), and R(d) with the traditional approach. Finally, the sequential nature of the calculations is replaced by calculating the EGP, R(a meal), and R(d) in "one go" to avoid the propagation of the errors from the EGP and R(a meal) into R(d). An example study is shown demonstrating the utility of the approach. A better performance of the new method is demonstrated in a simulation study.
authors.affiliation: Diabetes Modelling Group, Dept. of Paediatrics, Univ. of Cambridge, Box 116, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK. rh347@cam.ac.uk
authors.forename: Roman
authors.initials: R
authors.lastname: Hovorka
authors.forename: Harsha
authors.initials: H
authors.lastname: Jayatillake
authors.forename: Eduard
authors.initials: E
authors.lastname: Rogatsky
authors.forename: Vlad
authors.initials: V
authors.lastname: Tomuta
authors.forename: Tomas
authors.initials: T
authors.lastname: Hovorka
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Stein
mesh_terms: D001786:Blood Glucose / Q000032:analysis*; D019295:Computational Biology; D003198:Computer Simulation; D018149:Glucose Intolerance / Q000097:blood*; D005951:Glucose Tolerance Test; D006801:Humans; D008962:Models, Theoretical; D019518:Postprandial Period
chemical_list: D001786:Blood Glucose