TY - JOUR

T1 - Semimechanistic model describing gastric emptying and glucose absorption in healthy subjects and patients with type 2 diabetes

AU - Alskär, Oskar

AU - Bagger, Jonatan I

AU - Røge, Rikke M.

AU - Knop, Filip K.

AU - Karlsson, Mats O.

AU - Vilsbøll, Tina

AU - Kjellsson, Maria C.

PY - 2016/3

Y1 - 2016/3

N2 - 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.

AB - 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.

KW - gastric emptying

KW - glucose absorption

KW - integrated glucose-insulin model

KW - oral glucose tolerance test

KW - semimechanistic modeling

U2 - 10.1002/jcph.602

DO - 10.1002/jcph.602

M3 - Journal article

C2 - 26224050

AN - SCOPUS:84958108271

VL - 56

SP - 340

EP - 348

JO - Journal of Clinical Pharmacology

JF - Journal of Clinical Pharmacology

SN - 0091-2700

IS - 3

ER -