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.