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，NIDDM患者的葡萄糖有效性降低。自胰岛素以来 抵抗力和葡萄糖有效性受损可能在 NIDDM的发病机制，这些特性的定量评估是 利息。最近，一种涉及数学的最小模型方法 使用建模和计算机模拟来估计这两种胰岛素 单项试验结果的敏感性和葡萄糖有效性 经常进行静脉葡萄糖耐量试验(FSIVGTT)。这个 最小模型方程描述血糖的变化 浓度作为胰岛素和葡萄糖浓度的函数。一个 计算机程序识别生成最佳拟合度的模型参数 在FSIVGTT期间获得的胰岛素和血糖数据。因此，最低限度的 模型能够估计胰岛素和葡萄糖的相对贡献 与葡萄糖耐量有关。我们已经使用最小模型来生成特定的 胰岛素依赖型和非胰岛素依赖型血糖的预测 在各种条件下的代谢。我们在这里进行了实验 胰岛素依赖型糖尿病患者和正常人 测试一下这些预测。通过将模型预测与实验进行比较 结果，我们能够证明最小模型低估了 胰岛素的贡献和高估了葡萄糖的贡献 对葡萄糖代谢的影响。目前正在进行研究以证实这些 并了解最小和最小之间不协调的根源 模型预测和实验结果。我们收集的数据可能 允许我们制定一个更准确和更有用的数学模型。

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 samples 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.