Ellingsen Christian, Dassau Eyal, Zisser Howard, Grosman Benyamin, Percival Matthew W, Jovanovic Lois, Doyle Francis J
Department of Chemical Engineering, University of California at Santa Barbara, Santa Barbara, CA 93106-5080, USA.
J Diabetes Sci Technol. 2009 May 1;3(3):536-44. doi: 10.1177/193229680900300319.
Type 1 diabetes mellitus (T1DM) is characterized by the destruction of pancreatic beta cells, resulting in the inability to produce sufficient insulin to maintain normoglycemia. As a result, people with T1DM depend on exogenous insulin that is given either by multiple daily injections or by an insulin pump to control their blood glucose. A challenging task is to design the next step in T1DM therapy: a fully automated insulin delivery system consisting of an artificial pancreatic beta cell that shall provide both safe and effective therapy. The core of such a system is a control algorithm that calculates the insulin dose based on automated glucose measurements.
A model predictive control (MPC) algorithm was designed to control glycemia by controlling exogenous insulin delivery. The MPC algorithm contained a dynamic safety constraint, insulin on board (IOB), which incorporated the clinical values of correction factor and insulin-to-carbohydrate ratio along with estimated insulin action decay curves as part of the optimal control solution.
The results emphasized the ability of the IOB constraint to significantly improve the glucose/insulin control trajectories in the presence of aggressive control actions. The simulation results indicated that 50% of the simulations conducted without the IOB constraint resulted in hypoglycemic events, compared to 10% of the simulations that included the IOB constraint.
Achieving both efficacy and safety in an artificial pancreatic beta cell calls for an IOB safety constraint that is able to override aggressive control moves (large insulin doses), thereby minimizing the risk of hypoglycemia.
1型糖尿病（T1DM）的特征是胰腺β细胞被破坏，导致无法产生足够的胰岛素来维持正常血糖水平。因此，T1DM患者依赖通过每日多次注射或胰岛素泵给予的外源性胰岛素来控制血糖。一项具有挑战性的任务是设计T1DM治疗的下一步方案：一种由人工胰腺β细胞组成的全自动胰岛素输送系统，该系统应提供安全有效的治疗。这种系统的核心是一种基于自动血糖测量来计算胰岛素剂量的控制算法。
设计了一种模型预测控制（MPC）算法，通过控制外源性胰岛素输送来控制血糖。MPC算法包含一个动态安全约束，即体内胰岛素（IOB），它将校正因子和胰岛素与碳水化合物比值的临床值以及估计的胰岛素作用衰减曲线纳入最优控制解决方案中。
结果强调了IOB约束在存在激进控制行动时显著改善血糖/胰岛素控制轨迹的能力。模拟结果表明，在没有IOB约束的情况下进行的模拟中有50%导致了低血糖事件，而在包含IOB约束的模拟中这一比例为10%。
在人工胰腺β细胞中实现疗效和安全性需要一个能够超越激进控制行动（大剂量胰岛素）的IOB安全约束，从而将低血糖风险降至最低。
