Critical evaluation of the combined model approach for estimation
of pre-hepatic insulin secretion.
Watanabe, Richard M., Garry M. Steil, and Richard N. Bergman.
University of Southern California, Department of Exercise Science,
Los Angeles, CA, University of Southern California School of
Medicine, Department of Physiology & Biophysics, Los Angeles, CA
APStracts 4:0206E, 1997.
The Combined Model approach uses kinetic analysis of both plasma
insulin and C-peptide dynamics to estimate pre-hepatic insulin
secretion rates and parameters of insulin and C-peptide kinetics. The
original model utilized single compartment kinetics to describe both
insulin and C-peptide despite knowledge that C-peptide follows two
-compartment kinetics. The performance of the model under rapidly
changing secretory conditions has come into question. Thus, a more
complex Combined Model is introduced incorporating two compartmental
C-peptide disappearance. The addition of two-compartment C-peptide
kinetics required a novel numerical approach to allow estimation of
model parameters. This simulation study was undertaken to 1) compare
the performance of the original Combined Model and 2) examine the
numerical method used to identify parameters for the extended
Combined Model with two-compartment C-peptide kinetics under
simulated conditions of rapidly changing insulin and C-peptide.
Monte-Carlo simulation revealed that the original Combined Model does
not provide accurate estimates of pre-hepatic insulin secretion under
rapid kinetics. However, the extended Combined Model provides
accurate reconstruction of pre-hepatic insulin secretory profile
without separate quantification of C-peptide kinetics.
Received 4 April 1997; accepted in final form 18 September 1997.
APS Manuscript Number E155-7.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 7 October 1997