AJP - Endocrinology and Metabolism, Vol 270, Issue 3 E522-E531, Copyright © 1996 by American Physiological Society
Integrated mathematical model to assess beta-cell activity during the oral glucose test
K. Thomaseth, A. Kautzky-Willer, B. Ludvik, R. Prager and G. Pacini
Institute of Systems Science, Padua, Italy.
A model describing beta-cell secretion during an oral glucose tolerance
test (OGTT) is introduced. The aim was to quantify beta-cell activity in
different pathologies by analyzing peripheral concentration data of
insulin, C-peptide, and islet amyloid polypeptide (IAPP). Insulin
appearance in periphery is given by the fraction of C-peptide secretion,
CPS(t), which accounts for liver degradation. A novelty of this study is
the inclusion of IAPP delivery assumed proportional to CPS(t). Although
IAPP fractional clearance is estimated in every subject, the clearances of
insulin and C-peptide are assigned from a wide set of previous independent
studies. Sensitivity analysis was performed to quantify the "error" in the
estimated variables due to these assignments. All parameters relating to
beta-cell secretion increased in the glucose-intolerant states [integrated
CPS(t)=56 +/- 8 nmol/l in 180 min vs. 32 +/- 3 of controls, P<0.05;
total IAPP delivery= 83 +/- 21 pmol/l in 180 min vs. 41 +/- 6, P<0.05].
Elevated plasma IAPP concentration of the patients was due to augmented
secretion since IAPP clearance was found to be even slightly greater than
in controls, (0.053 +/- 0.011 vs. 0.034 +/- 0.004 min-1) and markedly lower
than that of insulin (0.14 +/- 0.02, P<0.01). In conclusion, the model
introduced here allows the characterization of beta-cell secretory
parameters during a simple test such as OGTT.
