Modelling the effects of glucagon during glucose tolerance testing
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Liverpool John Moores University; University of Dundee; University of Chester
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Background: Glucose tolerance testing is a tool used to estimate glucose effectiveness and insulin sensitivity in diabetic patients. The importance of such tests has prompted the development and utilisation of mathematical models that describe glucose kinetics as a function of insulin activity. The hormone glucagon, also plays a fundamental role in systemic plasma glucose regulation and is secreted reciprocally to insulin, stimulating catabolic glucose utilisation. However, regulation of glucagon secretion by α-cells is impaired in type-1 and type-2 diabetes through pancreatic islet dysfunction. Despite this, inclusion of glucagon activity when modelling the glucose kinetics during glucose tolerance testing is often overlooked. This study presents two mathematical models of a glucose tolerance test that incorporate glucose-insulin-glucagon dynamics. The first model describes a non-linear relationship between glucagon and glucose, whereas the second model assumes a linear relationship. Results: Both models are validated against insulin-modified and glucose infusion intravenous glucose tolerance test (IVGTT) data, as well as insulin infusion data, and are capable of estimating patient glucose effectiveness (sG) and insulin sensitivity (sI). Inclusion of glucagon dynamics proves to provide a more detailed representation of the metabolic portrait, enabling estimation of two new diagnostic parameters: glucagon effectiveness (sE) and glucagon sensitivity (δ). Conclusions: The models are used to investigate how different degrees of patient glucagon sensitivity and effectiveness affect the concentration of blood glucose and plasma glucagon during IVGTT and insulin infusion tests, providing a platform from which the role of glucagon dynamics during a glucose tolerance test may be investigated and predicted.Citation
Kelly, R. A., Fitches, M. J., Webb, S. D., Pop S. R. & Chidlow, S. J. (2019). Modelling the effects of glucagon during glucose tolerance testing. Theoretical Biology and Medical Modelling, 16, 21. https://doi.org/10.1186/s12976-019-0115-3Publisher
BMCAdditional Links
https://tbiomed.biomedcentral.com/articles/10.1186/s12976-019-0115-3Type
ArticleEISSN
1742-4682ae974a485f413a2113503eed53cd6c53
10.1186/s12976-019-0115-3
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Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0/