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In Silico Cloning of Target Type 2 Diabetes Population for Treatments Development and Decision Support*

机译:在计算机上克隆目标2型糖尿病人群,以开发治疗方法和决策支持*

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Therapies for treatment of type 2 diabetes (T2D) involve a variety of medications, depending on the stage of T2D progression. It is now an accepted knowledge that in silico trials can help to accelerate drug development and support treatment optimization. A T2D simulator (T2DS), consisting of a model of the glucose-insulin system and an in silico population describing glucose-insulin dynamics in T2D subjects, has been recently developed based on early-stage T2D data, studied with sophisticated experimental techniques. This limits the domain of validity of the simulator to this specific sub-population of T2D. Here we proposed a method for tuning the T2DS to any desired T2D target population, e.g. insulin-naïve (i.e., not experienced with insulin) patients, without the need to resort to complex and expensive clinical studies. This will allow to use the T2DS for testing treatments in the target population. To illustrate the methodology, we used a case study: extending the T2DS to reproduce the behavior of insulin-naïve T2D subjects. The methodology described here can be extended to other stages of T2D, allowing an extensive in silico testing phase of different treatments before human trials.
机译:根据T2D进展的阶段,用于治疗2型糖尿病(T2D)的疗法涉及多种药物。现在,人们已经知道,计算机模拟试验可以帮助加速药物开发并支持治疗优化。 T2D模拟器(T2DS)由葡萄糖-胰岛素系统模型和描述T2D受试者中葡萄糖-胰岛素动态的计算机群体组成,最近已根据早期T2D数据进行了开发,并通过复杂的实验技术进行了研究。这将模拟器的有效性范围限制为T2D的此特定子群体。在这里,我们提出了一种将T2DS调整为任何所需的T2D目标人群(例如目标人群)的方法。没有使用过胰岛素的患者(即没有使用过胰岛素的患者),而无需诉诸复杂且昂贵的临床研究。这将允许使用T2DS在目标人群中测试治疗方法。为了说明该方法,我们使用了一个案例研究:扩展T2DS以重现未使用胰岛素的T2D受试者的行为。此处介绍的方法可以扩展到T2D的其他阶段,从而可以在人体试验之前进行广泛的不同治疗的计算机测试阶段。

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