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- Alskär, Oskar, et al.
(författare)
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Semi-mechanistic model describing gastric emptying and glucose absorption in healthy subjects and patients with type 2 diabetes
- 2016
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Ingår i: Journal of clinical pharmacology. - : Wiley. - 0091-2700 .- 1552-4604. ; 56:3, s. 340-348
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Tidskriftsartikel (refereegranskat)abstract
- The integrated glucose-insulin (IGI) model is a previously published semi-mechanistic model, which 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 semi-physiological model developed performed better than previously published empirical models and allows for 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.
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- Røge, Rikke M, et al.
(författare)
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Modeling of 24-Hour Glucose and Insulin Profiles in Patients With Type 2 Diabetes Mellitus Treated With Biphasic Insulin Aspart
- 2014
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Ingår i: Journal of clinical pharmacology. - : Wiley. - 0091-2700 .- 1552-4604. ; 54:7, s. 809-817
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Tidskriftsartikel (refereegranskat)abstract
- Insulin therapy for diabetes patients is designed to mimic the endogenous insulin response of healthy subjects and thereby generate normal blood glucose levels. In order to control the blood glucose in insulin-treated diabetes patients, it is important to be able to predict the effect of exogenous insulin on blood glucose. A pharmacokinetic/pharmacodynamic model for glucose homoeostasis describing the effect of exogenous insulin would facilitate such prediction. Thus the aim of this work was to extend the previously developed integrated glucose-insulin (IGI) model to predict 24-hour glucose profiles for patients with Type 2 diabetes following exogenous insulin administration. Clinical data from two trials were included in the analysis. In both trials, 24-hour meal tolerance tests were used as the experimental setup, where exogenous insulin (biphasic insulin aspart) was administered in relation to meals. The IGI model was successfully extended to include the effect of exogenous insulin. Circadian variations in glucose homeostasis were assessed on relevant parameters, and a significant improvement was achieved by including a circadian rhythm on the endogenous glucose production in the model. The extended model is a useful tool for clinical trial simulation and for elucidating the effect profile of new insulin products.
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- Røge, Rikke M, et al.
(författare)
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The Effects of a GLP-1 Analog on Glucose Homeostasis in Type 2 Diabetes Mellitus Quantified by an Integrated Glucose Insulin Model
- 2015
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Ingår i: CPT. - : Wiley. - 2163-8306. ; 4:1, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- In recent years, several glucagon-like peptide-1 (GLP-1)-based therapies for the treatment of type 2 diabetes mellitus (T2DM) have been developed. The aim of this work was to extend the semimechanistic integrated glucose-insulin model to include the effects of a GLP-1 analog on glucose homeostasis in T2DM patients. Data from two trials comparing the effect of steady-state liraglutide vs. placebo on the responses of postprandial glucose and insulin in T2DM patients were used for model development. The effect of liraglutide was incorporated in the model by including a stimulatory effect on insulin secretion. Furthermore, for one of the trials an inhibitory effect on glucose absorption was included to account for a delay in gastric emptying. As other GLP-1 receptor agonists have similar modes of action, it is believed that the model can also be used to describe the effect of other receptor agonists on glucose homeostasis.
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