title: Integrated mathematical model to assess beta-cell activity during the oral glucose test.
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.
authors.affiliation: Institute of Systems Science, Padua, Italy.
authors.forename: K
authors.initials: K
authors.lastname: Thomaseth
authors.forename: A
authors.initials: A
authors.lastname: Kautzky-Willer
authors.forename: B
authors.initials: B
authors.lastname: Ludvik
authors.forename: R
authors.initials: R
authors.lastname: Prager
authors.forename: G
authors.initials: G
authors.lastname: Pacini
mesh_terms: D000682:Amyloid / Q000097:blood / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism*; D002096:C-Peptide / Q000097:blood / Q000378:metabolism*; D003907:Dexamethasone; D018149:Glucose Intolerance / Q000097:blood / Q000503:physiopathology*; D005951:Glucose Tolerance Test; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000503:physiopathology*; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D058228:Islet Amyloid Polypeptide; D007515:Islets of Langerhans / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008433:Mathematics; D008954:Models, Biological; D009765:Obesity / Q000097:blood / Q000503:physiopathology; D012016:Reference Values; D012044:Regression Analysis; D012680:Sensitivity and Specificity; D013997:Time Factors
chemical_list: D000682:Amyloid; D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D003907:Dexamethasone