title: Semimechanistic model describing gastric emptying and glucose absorption in healthy subjects and patients with type 2 diabetes.
abstract: The integrated glucose-insulin (IGI) model is a previously published semimechanistic model that describes plasma glucose and insulin concentrations after glucose challenges. The aim of this work was to use knowledge of physiology to improve the IGI model's description of glucose absorption and gastric emptying after tests with varying glucose doses. The developed model's performance was compared to empirical models. To develop our model, data from oral and intravenous glucose challenges in patients with type 2 diabetes and healthy control subjects were used together with present knowledge of small intestinal transit time, glucose inhibition of gastric emptying, and saturable absorption of glucose over the epithelium to improve the description of gastric emptying and glucose absorption in the IGI model. Duodenal glucose was found to inhibit gastric emptying. The performance of the saturable glucose absorption was superior to linear absorption regardless of the gastric emptying model applied. The semiphysiological model developed performed better than previously published empirical models and allows better understanding of the mechanisms underlying glucose absorption. In conclusion, our new model provides a better description and improves the understanding of dynamic glucose tests involving oral glucose.
authors.affiliation: Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
authors.forename: Oskar
authors.initials: O
authors.lastname: Alskär
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
authors.forename: Jonatan I
authors.initials: JI
authors.lastname: Bagger
authors.affiliation: Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.|Novo Nordisk A/S, Søborg, Denmark.
authors.forename: Rikke M
authors.initials: RM
authors.lastname: Røge
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
authors.forename: Filip K
authors.initials: FK
authors.lastname: Knop
authors.affiliation: Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
authors.forename: Mats O
authors.initials: MO
authors.lastname: Karlsson
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
authors.forename: Tina
authors.initials: T
authors.lastname: Vilsbøll
authors.affiliation: Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Kjellsson
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005746:Gastric Emptying / Q000187:drug effects; D065569:Gastrointestinal Absorption / Q000187:drug effects; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology; D005951:Glucose Tolerance Test; D064368:Healthy Volunteers; D006801:Humans; D007328:Insulin / Q000097:blood; D008954:Models, Biological
chemical_list: D001786:Blood Glucose; D007328:Insulin; D005947:Glucose
keywords: gastric emptying; glucose absorption; integrated glucose-insulin model; oral glucose tolerance test; semimechanistic modeling