An integrated glucose-insulin model to describe oral glucose tolerance test data in healthy volunteers.
The extension of the previously developed integrated models for glucose and insulin (IGI) to include the oral glucose tolerance test (OGTT) in healthy volunteers could be valuable to better understand the differences between healthy individuals and those with type 2 diabetes mellitus (T2DM). Data from an OGTT in 23 healthy volunteers were used. Analysis was based on the previously developed intravenous model with extensions for glucose absorption and incretin effect on insulin secretion. The need for additional structural components was evaluated. The model was evaluated by simulation and a bootstrap. Multiple glucose and insulin concentration peaks were observed in most individuals as well as hypoglycemic episodes in the second half of the experiment. The OGTT data were successfully described by the extended basic model. An additional control mechanism of insulin on glucose production improved the description of the data. The model showed good predictive properties, and parameters were estimated with good precision. In conclusion, a previously presented integrated model has been extended to describe glucose and insulin concentrations in healthy volunteers following an OGTT. The characterization of the differences between the healthy and diabetic stages in the IGI model could potentially be used to extrapolate drug effect from healthy volunteers to T2DM.
Silber
Hanna E
HE
Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden. hanna.silber@farmbio.uu.se
Frey
Nicolas
N
Karlsson
Mats O
MO
D000284:Administration, Oral; D001786:Blood Glucose / Q000378:metabolism*; D005947:Glucose / Q000008:administration & dosage* / Q000378:metabolism*; D005951:Glucose Tolerance Test / Q000379:methods* / Q000706:statistics & numerical data; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D008954:Models, Biological; D012016:Reference Values
D001786:Blood Glucose; D007328:Insulin; D005947:Glucose