Expansion of the homeostasis model assessment of β-cell function and insulin resistance to enable clinical trial outcome modeling through the interactive adjustment of physiology and treatment effects: iHOMA2.
Expansion of the homeostasis model assessment of β-cell function and insulin resistance to enable clinical trial outcome modeling through the interactive adjustment of physiology and treatment effects: iHOMA2.
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DOI：
10.2337/dc12-0607
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发表时间：
2013-08
期刊：
影响因子：
16.2
通讯作者：
Matthews DR
中科院分区：
文献类型：
--
作者：
Hill NR;Levy JC;Matthews DR
描述并提供交互式24变量稳态模型评估（iHOMA 2），该评估扩展了HOMA 2模型，能够对生理学和治疗效果进行建模，以呈现HOMA 2和iHOMA 2模型的方程，并在两种截然不同的情况下对iHOMA 2进行评估：噻唑烷二酮类药物引起的胰岛素敏感性变化和钠葡萄糖转运蛋白2（SGLT 2）抑制引起的肾阈值变化。iHOMA 2使可用软件的用户能够检查和修改描述葡萄糖和激素隔室中涉及的器官和组织的数学函数。我们使用已发表的肾脏效应数据通过SGLT 2抑制建模（通过改变肾脏阈值参数）对此进行了验证，表明建模效应与独立数据对空腹血糖的影响一致。噻唑烷二酮类效应的iHOMA 2建模表明，空腹状态下胰岛素敏感性的变化主要是肝脏的。通过iHOMA 2建模的SGLT 2抑制导致平均葡萄糖降低1.1 mmol/L。观察数据显示葡萄糖降低0.9 mmol/L。模型与独立数据之间无显著性差异。iHOMA 2的肾脏排泄阈值变量的操作表明，需要降低17%才能使平均葡萄糖降低0.9 mmol/L。iHOMA 2是用于评估胰岛素抵抗和β细胞功能的扩展数学模型。该模型可用于评估治疗剂并预测对空腹血糖和胰岛素以及对β细胞功能和胰岛素敏感性的影响。
To describe and make available an interactive, 24-variable homeostasis model assessment (iHOMA2) that extends the HOMA2 model, enabling the modeling of physiology and treatment effects, to present equations of the HOMA2 and iHOMA2 models, and to exemplify iHOMA2 in two widely differing scenarios: changes in insulin sensitivity with thiazolidinediones and changes in renal threshold with sodium glucose transporter 2 (SGLT2) inhibition. iHOMA2 enables a user of the available software to examine and modify the mathematical functions describing the organs and tissues involved in the glucose and hormonal compartments. We exemplify this with SGLT2 inhibition modeling (by changing the renal threshold parameters) using published data of renal effect, showing that the modeled effect is concordant with the effects on fasting glucose from independent data. iHOMA2 modeling of thiazolidinediones effect suggested that changes in insulin sensitivity in the fasting state are predominantly hepatic. SGLT2 inhibition modeled by iHOMA2 resulted in a decrease in mean glucose of 1.1 mmol/L. Observed data showed a decrease in glucose of 0.9 mmol/L. There was no significant difference between the model and the independent data. Manipulation of iHOMA2's renal excretion threshold variable suggested that a decrease of 17% was required to obtain a 0.9 mmol/L decrease in mean glucose. iHOMA2 is an extended mathematical model for the assessment of insulin resistance and β-cell function. The model can be used to evaluate therapeutic agents and predict effects on fasting glucose and insulin and on β-cell function and insulin sensitivity.
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影响因子：
5.8
作者：
Schernthaner, G;Matthews, DR;Brunetti, P
通讯作者：
Brunetti, P
影响因子：
--
作者：
COBELLI, C;PACINI, G;SACCA, L
通讯作者：
SACCA, L
影响因子：
7.7
作者：
COOK, JTE;PAGE, RCL;TURNER, RC
通讯作者：
TURNER, RC
影响因子：
8.2
作者：
HOSKER, JP;BURNETT, MA;TURNER, RC
通讯作者：
TURNER, RC
影响因子：
8.2
作者：
MATTHEWS, DR;HOSKER, JP;TURNER, RC
通讯作者：
TURNER, RC