Literature DB >> 19940230

An integrated glucose-insulin model to describe oral glucose tolerance test data in healthy volunteers.

Hanna E Silber1, Nicolas Frey, Mats O Karlsson.   

Abstract

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.

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Year:  2009        PMID: 19940230     DOI: 10.1177/0091270009341185

Source DB:  PubMed          Journal:  J Clin Pharmacol        ISSN: 0091-2700            Impact factor:   3.126


  20 in total

1.  Altered pattern of the incretin effect as assessed by modelling in individuals with glucose tolerance ranging from normal to diabetic.

Authors:  Andrea Tura; Elza Muscelli; Amalia Gastaldelli; Ele Ferrannini; Andrea Mari
Journal:  Diabetologia       Date:  2014-06       Impact factor: 10.122

2.  Mechanism-based population modelling of the effects of vildagliptin on GLP-1, glucose and insulin in patients with type 2 diabetes.

Authors:  Cornelia B Landersdorfer; Yan-Ling He; William J Jusko
Journal:  Br J Clin Pharmacol       Date:  2012-03       Impact factor: 4.335

Review 3.  Requirements for multi-level systems pharmacology models to reach end-usage: the case of type 2 diabetes.

Authors:  Elin Nyman; Yvonne J W Rozendaal; Gabriel Helmlinger; Bengt Hamrén; Maria C Kjellsson; Peter Strålfors; Natal A W van Riel; Peter Gennemark; Gunnar Cedersund
Journal:  Interface Focus       Date:  2016-04-06       Impact factor: 3.906

4.  Mechanism-based population modelling for assessment of L-cell function based on total GLP-1 response following an oral glucose tolerance test.

Authors:  Jonas B Møller; William J Jusko; Wei Gao; Torben Hansen; Oluf Pedersen; Jens J Holst; Rune V Overgaard; Henrik Madsen; Steen H Ingwersen
Journal:  J Pharmacokinet Pharmacodyn       Date:  2011-09-16       Impact factor: 2.745

5.  Application of the integrated glucose-insulin model for cross-study characterization of T2DM patients on metformin background treatment.

Authors:  Joanna Parkinson; Bengt Hamrén; Maria C Kjellsson; Stanko Skrtic
Journal:  Br J Clin Pharmacol       Date:  2016-08-16       Impact factor: 4.335

6.  Identification of the primary mechanism of action of an insulin secretagogue from meal test data in healthy volunteers based on an integrated glucose-insulin model.

Authors:  Steve Choy; Emilie Hénin; Jan-Stefan van der Walt; Maria C Kjellsson; Mats O Karlsson
Journal:  J Pharmacokinet Pharmacodyn       Date:  2012-11-24       Impact factor: 2.745

7.  Incorporation of stochastic variability in mechanistic population pharmacokinetic models: handling the physiological constraints using normal transformations.

Authors:  Nikolaos Tsamandouras; Thierry Wendling; Amin Rostami-Hodjegan; Aleksandra Galetin; Leon Aarons
Journal:  J Pharmacokinet Pharmacodyn       Date:  2015-05-26       Impact factor: 2.745

8.  Glucose Homeostatic Law: Insulin Clearance Predicts the Progression of Glucose Intolerance in Humans.

Authors:  Kaoru Ohashi; Hisako Komada; Shinsuke Uda; Hiroyuki Kubota; Toshinao Iwaki; Hiroki Fukuzawa; Yasunori Komori; Masashi Fujii; Yu Toyoshima; Kazuhiko Sakaguchi; Wataru Ogawa; Shinya Kuroda
Journal:  PLoS One       Date:  2015-12-01       Impact factor: 3.240

9.  Routine OGTT: a robust model including incretin effect for precise identification of insulin sensitivity and secretion in a single individual.

Authors:  Andrea De Gaetano; Simona Panunzi; Alice Matone; Adeline Samson; Jana Vrbikova; Bela Bendlova; Giovanni Pacini
Journal:  PLoS One       Date:  2013-08-29       Impact factor: 3.240

10.  Bariatric surgery and T2DM improvement mechanisms: a mathematical model.

Authors:  Puntip Toghaw; Alice Matone; Yongwimon Lenbury; Andrea De Gaetano
Journal:  Theor Biol Med Model       Date:  2012-05-15       Impact factor: 2.432

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