| 1. |
- Jauslin, Petra M, et al.
(författare)
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An integrated glucose-insulin model to describe oral glucose tolerance test data in type 2 diabetics
- 2007
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Ingår i: Journal of clinical pharmacology. - : Wiley. - 0091-2700 .- 1552-4604. ; 47:10, s. 1244-1255
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Silber, Hanna E, et al.
(författare)
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An integrated model for glucose and insulin regulation in healthy volunteers and type 2 diabetic patients following intravenous glucose provocations
- 2007
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Ingår i: Journal of clinical pharmacology. - : Wiley. - 0091-2700 .- 1552-4604. ; 47:9, s. 1159-1171
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Tidskriftsartikel (refereegranskat)abstract
- An integrated model for the regulation of glucose and insulin concentrations following intravenous glucose provocations in healthy volunteers and type 2 diabetic patients was developed. Data from 72 individuals were included. Total glucose, labeled glucose, and insulin concentrations were determined. Simultaneous analysis of all data by nonlinear mixed effect modeling was performed in NONMEM. Integrated models for glucose, labeled glucose, and insulin were developed. Control mechanisms for regulation of glucose production, insulin secretion, and glucose uptake were incorporated. Physiologically relevant differences between healthy volunteers and patients were identified in the regulation of glucose production, elimination rate of glucose, and secretion of insulin. The model was able to describe the insulin and glucose profiles well and also showed a good ability to simulate data. The features of the present model are likely to be of interest for analysis of data collected in antidiabetic drug development and for optimization of study design.
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| 3. |
- Silber, Hanna E., et al.
(författare)
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An Integrated Model for the Glucose-Insulin System
- 2010
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Ingår i: Basic & Clinical Pharmacology & Toxicology. - : Wiley. - 1742-7835 .- 1742-7843. ; 106:3, s. 189-194
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Forskningsöversikt (refereegranskat)abstract
- The integrated glucose-insulin model was originally developed on a variety of intravenous glucose provocation experiments in healthy volunteers and type 2 diabetic patients. The model, which simultaneously describes time-courses of glucose and insulin based on mechanism-based components for production, elimination and homeostatic feedback, has been further extended to oral glucose provocations, meal tests and insulin administration. The model has been used to describe experiments ranging from 4 to 24 hr. Applications of the integrated glucose-insulin model include the clinical assessment of the mechanism of action of anti-diabetic drugs and the magnitude of their effects. Finally, the model was used for optimizing the design of provocation experiments.
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