Hepatic glucose production during the labeled IVGTT: estimation by deconvolution with a new minimal model

A method for the estimation of hepatic glucose production during a labeled intravenous glucose tolerance test (IVGTT) is proposed. Stable-label IVGTT data in normal subjects have been considered. The method is based on deconvolution and uses a new two-compartment minimal model of glucose kinetics to describe the time-varying impulse response of the glucose system. A new model of glucose kinetics was needed because the available single-compartment minimal model, specifically developed to interpret labeled IVGTT data, provided a nonphysiological pattern of hepatic glucose production. The new minimal model has two novel features: glucose kinetics are described by a two-compartment structure, and insulin exerts its action on the irreversible loss of the slowly exchanging glucose pool. The deconvolution scheme used to reconstruct hepatic glucose production is described in detail both in terms of computational aspects and reliability. Confidence limits of the reconstructed hepatic glucose production in each individual are derived by taking into account both the measurement error of the data and the uncertainty associated with the description of the impulse response. Physiological plausibility of the time course of hepatic glucose production provided by this new method is discussed. The ability of the new model to reconstruct hepatic glucose production considerably enriches the kinetic portrait of glucose metabolism that can be obtained from the minimal-model analysis of labeled IVGTT data.