Modelling the effects of glucagon during glucose tolerance testing.

Q1 Mathematics
Ross A Kelly, Molly J Fitches, Steven D Webb, S R Pop, Stewart J Chidlow
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引用次数: 5

Abstract

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 pax'tient 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.

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模拟葡萄糖耐量试验中胰高血糖素的作用。
背景:葡萄糖耐量试验是一种评估糖尿病患者葡萄糖有效性和胰岛素敏感性的工具。这些测试的重要性促使了数学模型的发展和利用,这些模型将葡萄糖动力学描述为胰岛素活性的函数。激素胰高血糖素在全身血糖调节中也起着重要作用,并与胰岛素相互分泌,刺激分解代谢葡萄糖的利用。然而,在1型和2型糖尿病中,α-细胞对胰高血糖素分泌的调节通过胰岛功能障碍而受损。尽管如此,在葡萄糖耐量试验中模拟葡萄糖动力学时,胰高血糖素活性经常被忽视。本研究提出了葡萄糖耐量试验的两个数学模型,包括葡萄糖-胰岛素-胰高血糖素动力学。第一个模型描述了胰高血糖素和葡萄糖之间的非线性关系,而第二个模型假设了线性关系。结果:两种模型均通过胰岛素改良和葡萄糖输注静脉葡萄糖耐量试验(IVGTT)数据以及胰岛素输注数据进行验证,并能够估计患者的葡萄糖有效性(sG)和胰岛素敏感性(sI)。包括胰高血糖素动力学证明提供了代谢画像的更详细的表示,使两个新的诊断参数的估计:胰高血糖素有效性(sE)和胰高血糖素敏感性(δ)。结论:该模型用于研究不同程度的患者胰高血糖素敏感性和有效性对IVGTT和胰岛素输注试验中血糖和血浆胰高血糖素浓度的影响,为研究和预测葡萄糖耐量试验中胰高血糖素动力学的作用提供了平台。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Theoretical Biology and Medical Modelling
Theoretical Biology and Medical Modelling MATHEMATICAL & COMPUTATIONAL BIOLOGY-
自引率
0.00%
发文量
0
审稿时长
6-12 weeks
期刊介绍: Theoretical Biology and Medical Modelling is an open access peer-reviewed journal adopting a broad definition of "biology" and focusing on theoretical ideas and models associated with developments in biology and medicine. Mathematicians, biologists and clinicians of various specialisms, philosophers and historians of science are all contributing to the emergence of novel concepts in an age of systems biology, bioinformatics and computer modelling. This is the field in which Theoretical Biology and Medical Modelling operates. We welcome submissions that are technically sound and offering either improved understanding in biology and medicine or progress in theory or method.
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