An integrated glucose-insulin model to describe oral glucose tolerance test data in type 2 diabetics.
An integrated model for the glucose-insulin system describing oral glucose tolerance test data was developed, extending on a previously introduced model for intravenous glucose provocations. Model extensions comprised the description of glucose absorption by a chain of transit compartments with a mean transit time of 35 minutes, a bioavailability of 80%, and a representation of the incretin effect, expressed as a direct effect of the glucose absorption rate on insulin secretion. The ability of the model to predict the incretin effect was assessed by simulating the observed difference in insulin response following an oral glucose tolerance test compared with an isoglycemic glucose infusion mimicking an oral glucose tolerance test profile. The extension of the integrated glucose-insulin model to gain information from oral glucose tolerance test data considerably expands its range of applications because the oral glucose tolerance test is one of the most common glucose challenge experiments for assessing the efficacy of hypoglycemic agents in clinical drug development.
Jauslin
Petra M
PM
Department of Pharmaceutical Biosciences, Division of Pharmacokinetics and Drug Therapy, University of Uppsala, Friggs Grand 4, Halmstad, Sweden.
Silber
Hanna E
HE
Frey
Nicolas
N
Gieschke
Ronald
R
Simonsson
Ulrika S H
US
Jorga
Karin
K
Karlsson
Mats O
MO
D003198:Computer Simulation; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D015195:Drug Design; D005260:Female; D005947:Glucose / Q000096:biosynthesis / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D008954:Models, Biological
D007328:Insulin; D005947:Glucose