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 ( s _G ) and insulin sensitivity ( s _I ). Inclusion of glucagon dynamics proves to provide a more detailed representation of the metabolic portrait, enabling estimation of two new diagnostic parameters: glucagon effectiveness ( s _E ) 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.



中文翻译：

---

建模胰高血糖素在葡萄糖耐量测试期间的作用

背景技术
葡萄糖耐量测试是一种用于评估糖尿病患者的葡萄糖有效性和胰岛素敏感性的工具。这种测试的重要性促使人们开发和利用数学模型来描述葡萄糖动力学与胰岛素活性之间的关系。胰高血糖素激素在全身性血浆葡萄糖调节中也起着基本作用，并与胰岛素相互分泌，从而刺激分解代谢葡萄糖的利用。然而， α 调节胰高血糖素的分泌 胰岛功能异常在1型和2型糖尿病中会损害-细胞。尽管如此，在葡萄糖耐量测试过程中对葡萄糖动力学建模时，胰高血糖素活性通常被忽略。这项研究提出了两个葡萄糖耐量测试的数学模型，其中包含了葡萄糖-胰岛素-胰高血糖素的动力学。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，而第二个模型则假定了线性关系。

结果
两种模型均针对胰岛素修饰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了验证，并且能够估计患者的葡萄糖有效性（ s _G ）和胰岛素敏感性（ s _I ）。包含胰高血糖素动力学被证明可以提供代谢肖像的更详细表示，从而可以估算两个新的诊断参数：胰高血糖素有效性（ s _E ）和胰高血糖素敏感性（ δ ）。结论该模型用于研究不同程度的胰高血糖素敏感性和有效性如何在IVGTT和胰岛素输注测试中影响血糖和血浆胰高血糖素的浓度，从而提供一个平台，从中可以了解胰高血糖素动力学在葡萄糖耐量测试中的作用。被调查和预测。