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

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.