Glucose production during an IVGTT by deconvolution: validation with the tracer-to-tracee clamp technique

Recently, a new method, based on a two-compartment minimal model and deconv olution [A. Caumo and C. Cobelli. Am. J. Physiol 264 (Endocrinol. Metab.. 3 7): E829-E841, 1993; P. Vicini, G. Sparacino, A. Caumo, and C. Cobelli. Com put. Meth. Frog. Biomed. 52: 147-156, 1997], has been proposed to estimate endogenous glucose production (EGP) from labeled intravenous glucose tolera nce test (IVGTT) data. Our aim here is to compare this EGP profile with tha t independently obtained with the reference method, based on the tracer-to- tracee ratio (TTR) clamp. An insulin-modified (0.03 U/kg body wt infused ov er 5 min) [6,6-H-2(2)]glucose-labeled IVGTT (0.33 g/kg of glucose) was perf ormed in 10 normal subjects. A second tracer ([U-C-13]glucose) was also inf used during the test in a variable fashion to clamp endogenous glucose TTR. The TTR clamp was quite successful. As a result, the EGP profile, reconstr ucted from [U-C-13]glucose data with the models of Steele and Radziuk, were almost superimposable. The deconvolution-obtained EGP profile, calculated from [6,6-H-2(2)]glucose data, showed remarkable agreement with that obtain ed from the TTR clamp. Some differences between the two profiles were noted in the estimated basal EGP and in the initial modalities of EGP inhibition . A high interindividual variability was also observed with both methods in the resumption of EGP to baseline; variability was high in both the timing and the extent of resumption. In conclusion, the use of the two-compartmen t minimal model of the IVGTT and deconvolution allows the estimation of a p rofile of EGP that is in very good agreement with that independently obtain ed with a TTR clamp.