Mechanical Engineering Department, University of New Mexico, Albuquerque, NM 87131, United States of America.
PLoS One. 2019 Mar 20;14(3):e0213665. doi: 10.1371/journal.pone.0213665. eCollection 2019.
The Glucose-Insulin-Glucagon nonlinear model accurately describes how the body responds to exogenously supplied insulin and glucagon in patients affected by Type I diabetes. Based on this model, we design infusion rates of either insulin (monotherapy) or insulin and glucagon (dual therapy) that can optimally maintain the blood glucose level within desired limits after consumption of a meal and prevent the onset of both hypoglycemia and hyperglycemia. This problem is formulated as a nonlinear optimal control problem, which we solve using the numerical optimal control package [Formula: see text]. Interestingly, in the case of monotherapy, we find the optimal solution is close to the standard method of insulin based glucose regulation, which is to assume a variable amount of insulin half an hour before each meal. We also find that the optimal dual therapy (that uses both insulin and glucagon) is better able to regulate glucose as compared to using insulin alone. We also propose an ad-hoc rule for both the dosage and the time of delivery of insulin and glucagon.
葡萄糖-胰岛素-胰高血糖素非线性模型准确描述了 1 型糖尿病患者对外源性胰岛素和胰高血糖素的反应。基于该模型,我们设计了胰岛素(单药治疗)或胰岛素和胰高血糖素(双药治疗)的输注率,这些输注率可以在进食后最佳地将血糖水平维持在所需范围内,并预防低血糖和高血糖的发生。这个问题被表述为一个非线性最优控制问题,我们使用数值最优控制包 [公式:见正文] 来解决。有趣的是,在单药治疗的情况下,我们发现最优解接近于基于胰岛素的葡萄糖调节的标准方法,即在每餐前半小时假设一定量的胰岛素。我们还发现,与单独使用胰岛素相比,最优的双药治疗(同时使用胰岛素和胰高血糖素)更能调节血糖。我们还提出了一个关于胰岛素和胰高血糖素剂量和输送时间的临时规则。