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INNOVATIVE METHODOLOGY

Calculating glucose fluxes during meal tolerance test: a new computational approach

¹Department of Paediatrics, University of Cambridge, Cambridge, United Kingdom; ²Department of Medicine, Division of Endocrinology; and ³General Clinical Research Center Analytical Core Laboratory, Albert Einstein College of Medicine, Bronx, New York

Submitted 8 October 2006 ; accepted in final form 11 May 2007

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.

glucose kinetics; gut absorption; endogenous glucose production; glucose tracer; mathematical modeling

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