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Am J Physiol Endocrinol Metab (May 22, 2007). doi:10.1152/ajpendo.00546.2006
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Submitted on October 8, 2006
Accepted on May 11, 2007

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

Roman Hovorka1*, Harsha Jayatillake2, Eduard Rogatsky2, Vlad Tomuta3, Tomas Hovorka1, and Daniel T. Stein4

1 Paediatrics, University of Cambridge, Cambridge, United Kingdom
2 Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, United States
3 Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, United States; Medicine, Albert Einstein College of Medicine, Bronx, New York, United States
4 Department of Medicine, Endocrinology Division, Albert Einstein College of Medicine, Bronx, New York, United States

* To whom correspondence should be addressed. E-mail: rh347{at}cam.ac.uk.

A new calculation method is proposed to quantify the endogenous glucose production (EGP), the glucose appearance rate due to meal ingestion (Ra meal), and the glucose disposal (Rd) during a three-tracer study design. The method utilises the maximum likelihood theory combined with a regularisation method to achieve a theoretically coherent computational framework. The method uses the two-compartment formulation of the glucose kinetics. Instead of assuming smoothness of unlabelled and labelled glucose concentrations, the method assumes that the EGP, the Ra 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, Ra meal, and Rd with the traditional approach. Finally, the sequential nature of the calculations is replaced by calculating the EGP, Ra meal, and Rd in "one go" to avoid the propagation of the errors from the EGP and Ra meal into Rd. An example study is shown demonstrating the utility of the approach. A better performance of the new method is demonstrated in a simulation study.




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