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Ds-optimal design of an integrated minimal model for the intravenous glucose tolerance test
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. (Farmakometri)
2017 (English)Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
Abstract [en]

Introduction: In diabetes research, the intravenous glucose tolerance test (IVGTT) with the minimal model can derive the key diagnosis parameters glucose effectiveness (SG) and insulin sensitivity (SI). The model is limited by being a coupled two-part model, conditioned on either glucose or insulin, which increases the requirement of blood samples. Hence, integrated models that combine the glucose and insulin part into one model have been established, which should enable a decrease in blood samples for estimation of SG and SI. A statistical method called optimal design, which is based on the concept of Fisher information, could derive optimized study designs from such a model. Aim: To optimize the study design of a recently constructed integrated minimal model with respect to the parameters SG and SI and show that the model could be used with the IVGTT with sparser sample times. Methods: Optimization was performed using the PopED package in R, with a compiled section of the script written in C for faster computation. The DS optimality criterion was used for optimization, and the parameters which affected SG and SI was chosen as interesting parameters. Results: Simultaneous optimization of dose and dose time for glucose, amount, time and duration of insulin infusion, and sample times, showed a large increase in efficiency of the model. Removing duplicate sample times of the optimized study design (from 32 to 12) still showed 30 times higher efficiency than the original design. With fixed glucose and insulin inputs to prevent hypoglycemia, an optimization of a 10 sample study design showed improved efficiency. Conclusion: Optimal design of the new integrated minimal model could substantially improve the study design of IVGTT.

Place, publisher, year, edition, pages
2017. , 37 p.
Keyword [en]
Optimal design, intravenous glucose tolerance test, pharmacometrics
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-325532OAI: oai:DiVA.org:uu-325532DiVA: diva2:1115134
Subject / course
Pharmacokinetics
Educational program
Master of Science Programme in Pharmacy
Supervisors
Examiners
Available from: 2017-06-29 Created: 2017-06-26 Last updated: 2017-06-29Bibliographically approved

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  • nn-NB
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