MATHEMATICAL MODELING OF GLUCOSE METABOLISM

葡萄糖代谢的数学模型

• 批准号: 5202022
• 负责人: M QUON
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5202022
• 关键词: computer simulation; glucose metabolism; glucose tolerance test; hormone regulation /control mechanism; human subject; insulin; insulin dependent diabetes mellitus; insulin sensitivity /resistance; mathematical model; model design /development; noninsulin dependent diabetes mellitus

Insulin resistance occurs in a variety of pathological states including obesity, non-insulin dependent diabetes mellitus (NIDDM) and hypertension. Decreased glucose effectiveness has been reported in NIDDM. Since insulin resistance and impaired glucose effectiveness may play a role in the pathogenesis of NIDDM, quantitative assessment of these properties is of interest. Recently, a minimal model approach involving mathematical modeling and computer simulation has been used to estimate both insulin sensitivity and glucose effectiveness from the results of a single frequently sample intravenous glucose tolerance test (FSIVGTT). The equations of the minimal model describe changes in plasma glucose concentration as functions of insulin and glucose concentrations. A computer program identifies model parameters that generate a best fit to insulin and glucose data obtained during the FSIVGTT. Thus, the minimal model is able to estimate the relative contributions of insulin and glucose to glucose tolerance. We have used the minimal model to generate specific predictions of both insulin-dependent and insulin- independent glucose metabolism under a variety of conditions. We performed experiments in subjects with insulin dependent diabetes mellitus and in normal subjects to test these predictions. By comparing model predictions with experimental results, we were able to demonstrate that the minimal model underestimates the contributions of insulin and overestimates the contribution of glucose to glucose metabolism. Studies are presently underway to confirm these results and to understand the origin of the discordance between minimal model predictions and experimental results. The data that we collect may allow us to formulate a more accurate and useful mathematical model.

胰岛素抵抗发生在多种病理状态中，包括 肥胖、非胰岛素依赖型糖尿病（NIDDM）和 高血压 据报告，葡萄糖有效性降低， NIDDM。 由于胰岛素抵抗和葡萄糖有效性受损可能 在NIDDM的发病机制中发挥作用，定量评估 这些性质是令人感兴趣的。 最近，最小模型方法 包括数学建模和计算机模拟， 从胰岛素敏感性和葡萄糖有效性评估 单次频繁采样静脉葡萄糖耐量试验结果 （FSIVGTT）。 最小模型的方程描述了等离子体的变化 葡萄糖浓度作为胰岛素和葡萄糖浓度的函数。 计算机程序识别产生最佳拟合的模型参数， FSIVGTT期间获得的胰岛素和葡萄糖数据。 因此 最小模型能够估计胰岛素的相对贡献 和葡萄糖对葡萄糖耐量。 我们使用最小模型来 产生胰岛素依赖性和胰岛素依赖性的特定预测， 在各种条件下独立的葡萄糖代谢。 我们 在胰岛素依赖型糖尿病患者中进行实验 在正常人中测试这些预测。 通过比较 模型预测与实验结果，我们能够证明， 最小模型低估了胰岛素的贡献， 高估了葡萄糖对葡萄糖代谢的贡献。 研究 目前正在确认这些结果，并了解 最小模型预测之间不一致的根源， 试验结果 我们收集的数据可以让我们制定 一个更精确、更有用的数学模型。