Integrated mathematical model to assess beta-cell activity during the oral glucose test

Am J Physiol. 1996 Mar;270(3 Pt 1):E522-31. doi: 10.1152/ajpendo.1996.270.3.E522.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid / blood
  • Amyloid / metabolism
  • Blood Glucose / metabolism*
  • C-Peptide / blood
  • C-Peptide / metabolism*
  • Dexamethasone
  • Glucose Intolerance / blood
  • Glucose Intolerance / physiopathology*
  • Glucose Tolerance Test*
  • Humans
  • Hypertension / blood
  • Hypertension / physiopathology*
  • Insulin / blood
  • Insulin / metabolism*
  • Insulin Secretion
  • Islet Amyloid Polypeptide
  • Islets of Langerhans / metabolism*
  • Kinetics
  • Liver / metabolism
  • Mathematics
  • Models, Biological*
  • Obesity / blood
  • Obesity / physiopathology
  • Reference Values
  • Regression Analysis
  • Sensitivity and Specificity
  • Time Factors

Substances

  • Amyloid
  • Blood Glucose
  • C-Peptide
  • Insulin
  • Islet Amyloid Polypeptide
  • Dexamethasone