Closed-loop subcutaneous insulin infusion algorithm with a short-acting insuin analog for long-term clinical application of a wearable artificial endocrine pancreas.

考虑到可穿戴式人工内分泌胰腺长期应用于非卧床糖尿病患者的胰岛素输注途径的管理和安全性，我们通过三室模型分析了皮下注射短效胰岛素类似物(Insulin Lipro)的动力学，提出了一种皮下胰岛素输注算法。大体上，胰岛素输注算法被发展为一个传递函数，在与血糖浓度成比例和导数的作用中都具有一阶延迟。该算法的参数被计算来尽可能地模拟生理血浆胰岛素谱。与计算机模拟研究一样，将该算法应用于常规胰岛素，糖尿病患者表现出餐后2小时的高血糖和延迟性的高胰岛素血症，随后在口服葡萄糖负荷后4-5小时内出现低血糖发作。然而，使用胰岛素利斯普罗，一个近生理的血糖控制(餐后血糖153.1(]sy.+.[]8.3毫克/100毫升，60分钟，90.3毫克/100毫升。[分别为7.1 mg/100ml，180min]，未出现迟发性高胰岛素血症和低血糖。每天的血糖漂移也被控制在接近生理的水平，并通过每日胰岛素需求量(731.7(]sy.+-)控制。[160.5 mU/kg/d]略高，但与静脉注射胰岛素(622.3 mU/kg/d)无显著差异。[142.6 MU/kg/d]。这些结果表明，在非卧床糖尿病患者使用可穿戴式人工内分泌胰腺进行长期血糖控制时，应用胰岛素利普罗皮下注射算法是可行的。

Considering the management and safety of the insulin delivery route when a wearable artificial endocrine pancreas is applied to ambulatory diabetic patients for long-term basis, we developed a subcutaneous insulin infusion algorithm by analyzing the dynamics of subcutaneously injected short-acting insulin analogue (Insulin Lispro) by a three-compartmental model. Principally, the insulin infusion algorithm was developed as a transfer function with the first order delay in both proportional and derivative actions to blood glucose concentrations. The parameters for this algorithm were calculated to simulate a physiological plasma insulin profile as possible.By applying this algorithm with regular insulin, diabetic patients showed a 2-hr postprandial hyperglycemia and a delayd hyperinsulinemia, folowed by hypoglycemic episodes during 4 to 5 hr after oral glucose load, just as obervrd in computer simulation study. However using Insulin Lispro, a near-physiological glycemic control (postprandial blood glucose of 153.1(]SY.+-。[)8.3 mg/100 ml at 60 min, and 90.3(]SY.+-。[)7.1 mg/100 ml at 180 min, respectively) could be achieved without showing any delayd hyperinsulinemia nor hypoglycemia. Daily glycemic excursions were also controlled near-physiolosically and though the daily insulin requirement (731.7(]SY.+-。[)160.5 mU/kg/day) was slightly higher, but not significantly different from that with intravenous insulin infusion (622.3(]SY.+-。[)142.6 mU/kg/day).These results indicate that the application of the subcutaneous insulin infusion algorithm with Insulin Lispro is feasible for long-term glycemic control with the wearable artificial endocrine pancreas in ambulatory diabetic patients.