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时胰岛素输注途径的管理和安全性，我们通过分析皮下注射短效胰岛素类似物（赖脯胰岛素）的动力学，采用三室模型，开发了一种皮下胰岛素输注算法。原则上，胰岛素输注算法被开发为在与血糖浓度的比例和微分作用中具有一阶延迟的传递函数。计算该算法的参数以尽可能模拟生理血浆胰岛素曲线，将该算法应用于常规胰岛素，糖尿病患者出现餐后2小时高血糖和延迟性高胰岛素血症，并在口服葡萄糖负荷后4 ~ 5小时内出现低血糖发作，与计算机模拟研究结果一致。然而，使用赖脯胰岛素，一种接近生理的血糖控制（餐后血糖为153.1（± SD））。[)8.3 60 min时，90.3mg/100 ml; [)7.1 180 min时分别为100 mg/100 ml），未显示任何迟发性高胰岛素血症或低血糖。每日血糖波动也接近生理控制，尽管每日胰岛素需求量（731.7（± SY））。[] 160.5 mU/kg/d）略高，但与静脉输注胰岛素（622.3（]SY. ±. [142.6 mU/kg/天）。这些结果表明，赖脯胰岛素皮下胰岛素输注算法的应用对于非卧床糖尿病患者使用可穿戴人工内分泌胰腺进行长期血糖控制是可行的。

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.