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Structural identifiability and indistinguishability analyses of glucose-insulin models
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Chin, Sze Vone (2011) Structural identifiability and indistinguishability analyses of glucose-insulin models. PhD thesis, University of Warwick.
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WRAP_THESIS_Chin_2011.pdf - Submitted Version - Requires a PDF viewer. Download (2702Kb) |
Official URL: http://webcat.warwick.ac.uk/record=b2533291~S1
Abstract
In this thesis, the structural identifiability analyses of established and novel
glucose-insulin models was performed, to determine whether the models are
globally structurally identifiable with the observations available. Structural
identifiability analysis is an essential step in the modelling process and a key
prerequisite to experimental design and parameter estimation. Analyses were
performed assuming observations of both glucose and insulin concentrations
on two versions of the well-cited Minimal Model (MM), the Original Minimal
Model (OMM) and Extended Minimal Model (EMM) for the modelling of the
responses to an Intravenous Glucose Tolerance Test (IVGTT); a Euglycemic
Hyperinsulinemic Clamp model and two novel modified versions of the MM,
a Closed-Loop Minimal Model (CLMM) and a Double-Pole in Closed-Loop
Minimal Model (DPCLMM), when the models describe a complete course of
glucose-insulin dynamics during an IVGTT. The CLMM proved to be unidentifiable so a reparameterisation procedure was performed on this model, yielding
a globally structurally identifiable reparameterised model. Parameter estimation
using these models was also performed for sets of IVGTT and glucose
clamp data. The results of the parameter estimation demonstrated that global
structural identifiability does not as always guarantee numerical identifiability,
or vice versa. A structural indistinguishability analysis was also performed to
compare the MM and the CLMM, given the same observations, where it was
shown that both models are distinguishable over both pre- and post- insulin
switching phases. This is the first time that all such analyses have been performed
on these specific model structures. The generic and numerical results
obtained demonstrate issues that may arise in practice when attempting to
calculate insulin sensitivity when using such models.
Item Type: | Thesis (PhD) | ||||
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Subjects: | Q Science > QA Mathematics R Medicine > RC Internal medicine |
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Library of Congress Subject Headings (LCSH): | Insulin -- Physiological effect -- Mathematical models, Blood sugar -- Mathematical models | ||||
Official Date: | May 2011 | ||||
Dates: |
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Institution: | University of Warwick | ||||
Theses Department: | School of Engineering | ||||
Thesis Type: | PhD | ||||
Publication Status: | Unpublished | ||||
Supervisor(s)/Advisor: | Chappell, Michael John, 1960- | ||||
Extent: | xiv, 210 leaves : charts | ||||
Language: | eng |
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