Nonmem improves group parameter estimation for the minimal model of
glucose kinetics.
Gaetano, Andrea De, Geltrude Mingrone, Marco Castagneto,.
CNR - Centro Studio Fisiopatologia Shock - Rome, Divisione di
Malattie Metaboliche, Clinica Medica, Universit[grave]a Cattolica -
Rome
APStracts 3:0144E, 1996.
The minimal model of glucose kinetics interprets blood glucose and
insulin concentrations after an intravenous Glucose Tolerance Test
(IVGTT) and provides parameters describing tissue insulin sensitivity
and glucose-dependent tissue glucose disposal. In the standard
application, the model is fitted to each experimental subject's
points by non-linear least squares, with suitable weighing. The
variability of parameter estimates may however represent a problem,
making the model in practice unidentifiable on a group of
experimental subjects undergoing some treatment of interest. In order
to obviate this problem, a specific modification to the original
protocol has been introduced: administering tolbutamide 20 minutes
after the glucose bolus has been shown to improve parameter
stability. With this modification, however, the converse model of
pancreatic secretion can no more be fitted on the collected series of
concentrations. The application of the NONlinear Mixed Effects Model
(NONMEM) loss function allows estimation of parameter population
means, variances and covariances to be made on all sampled subjects
simultaneously. While this procedure does not allow an individual
subject's parameters to be estimated, the variability of the group
parameter estimates is greatly reduced with respect to the standard
method. In the present work, twenty healthy volunteers have been
studied with an IVGTT and group parameters have been computed in both
standard and NONMEM ways: asymptotic parameter coefficients of
variation with NONMEM were more than twenty times smaller than the
corresponding sample parameter coefficients of variation obtained
with the classical method.
Received 5 August 1996; accepted in final form 14 June 1996.
APS Manuscript Number E291-3.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 July 1996