MATHEMATICAL MODELING OF GLUCOSE METABOLISM

胰岛素抵抗发生在各种病理状态，包括 肥胖、非胰岛素依赖型糖尿病(NIDDM)和 高血压。据报道，葡萄糖的有效性在 NIDDM。由于胰岛素抵抗和葡萄糖有效性受损可能 在NIDDM发病机制中的作用，定量评估 这些特性令人感兴趣。最近，一种最小模型方法 涉及数学建模和计算机模拟的方法已经被用来 估计胰岛素敏感性和葡萄糖有效性从 单份频繁样本静脉葡萄糖耐量试验结果分析 (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。 计算机程序识别生成最佳拟合的模型参数 在FSIVGTT期间获得的胰岛素和血糖数据。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的影响。我们已经使用最小模型来 产生对胰岛素依赖和胰岛素的特定预测- 在各种条件下独立的葡萄糖代谢。我们 对患有胰岛素依赖型糖尿病的受试者进行实验 并在正常受试者中测试这些预测。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和 高估了葡萄糖对葡萄糖代谢的贡献。研究 目前正在进行以确认这些结果并理解 最小模型预测与最小模型预测之间不一致的根源 实验结果。我们收集的数据可能会让我们 一个更准确、更有用的数学模型。

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.