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

采用短效胰岛素类似物的闭环皮下胰岛素输注算法，用于可穿戴人工内分泌胰腺的长期临床应用。

• 批准号: 08680930
• 负责人: SAKAKIDA Miciharu
• 金额: $ 1.6万
• 依托单位: KUMAMOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08680930/
• 关键词: closed-loop subcutaneous insulin infusion algorithm; wearable artificial endocrine pancreas; short-acting insulin analogue (Insulin Lispro); regular insulin

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.

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。

项目成果

S.Shimoda, K.Nishida, M.Sakakida et al.: "The clinical application of closed-loop subcutaneous insulin infusion algorithm with short-acting insulin analogue for wearable artificial endocrine pancreas." Jpn J Artif Organs. 26(3). 739-743 (1997)

S.Shimoda、K.Nishida、M.Sakakida 等人：“短效胰岛素类似物闭环皮下胰岛素输注算法在可穿戴人工内分泌胰腺中的临床应用”。

七里元亮ら: "人工膵島の現況と課題" 総合臨床. 46(11). 2809-2815 (1997)

Motosuke Shichiri 等人：“人工胰岛的现状和问题”《一般临床实践》46(11) (1997)。

S.Shimoda, K.Nishida, M.Sakakida et al.: "Closed-loop subcutaneous insulin infusion algorithm with a short-acting insulin analogue for long-term clinical application of a wearable artificial endocrine pancreas." Frontiers Med.Biol.Engng. 8(3). 197-211 (19

S.Shimoda、K.Nishida、M.Sakakida 等人：“采用短效胰岛素类似物的闭环皮下胰岛素输注算法，用于可穿戴人工内分泌胰腺的长期临床应用。”

S.Shimoda, K.Nishida, M.Sakakida, Y.Konno, K.Ichinose, T.Uehara, T.Nowak & M.Shichiri: "Closed-loop subcutaneous insulin infusion algorithm with a short-acting insulin analogue for long-term clinical application of a wearable artificial endocrine pancreas

S.Shimoda、K.Nishida、M.Sakakida、Y.Konno、K.Ichinose、T.Uehara、T.Nowak

今野由美ら: "携帯型人工膵島の長期臨床応用" 日本臨床. 55(725). 282-287 (1997)

Yumi Konno 等：“便携式人工胰岛的长期临床应用”日本临床研究 55(725) 282-287 (1997)。