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 lab eled intravenous glucose tolerance test (IVGTT) is proposed. Stable-la bel 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 th e available single-compartment minimal model, specifically developed t o interpret labeled IVGTT data, provided a nonphysiological pattern of hepatic glucose production. The new minimal model has two novel featu res: glucose kinetics are described by a two-compartment structure, an d insulin exerts its action on the irreversible loss of the slowly exc hanging glucose pool. The deconvolution scheme used to reconstruct hep atic glucose production is described in detail both in terms of comput ational aspects and reliability. Confidence limits of the reconstructe d hepatic glucose production in each individual are derived by taking into account both the measurement error of the data and the uncertaint y associated with the description of the impulse response. Physiologic al plausibility of the time course of hepatic glucose production provi ded by this new method is discussed. The ability of the new model to r econstruct hepatic glucose production considerably enriches the kineti c portrait of glucose metabolism that can be obtained from the minimal -model analysis of labeled IVGTT data.