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Development of closed-loop intraperitoneal insulin infusion algorithm -for long-term application of an implantable artificial endocrine pancreas-

闭环腹腔胰岛素输注算法的开发-用于植入式人工内分泌胰腺的长期应用-

基本信息

批准号：
14580825
负责人：
SAKAKIDA Michiharu
金额：
$ 2.56万
依托单位：
k
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

项目摘要

The ultimate goal of the development of an artificial endocrine pancreas is to achieve a long-term strict glycemic regulation. In order to establish the physiological insulin delivery route of the artificial endocrine pancreas, intraperitoneal insulin infusion may be important. For this purpose, we tried to develop closed-loop intraperitoneal insulin infusion algorithm by analyzing the pharmacokinetics of intraperitoneal regular insulin absorption using a mathematical model. The parameters for this algorithm were calculated to simulate the plasma insulin profile after intraperitoneal insulin injection as closely as possible. To evaluate the appropriateness of this algorithm, we tried glycemic control after 2-g/kg oral glucose load or 80-kcal/kg meal load in diabetic dogs by applying the algorithm. Using the subcutaneous insulin lispro infusion algorithm, which we have previously reported, alloxan-induced diabetic dogs exhibited postprandial hyperglycemia and delayed hyperinsulinemia, f … More ollowed by hypoglycemia after 2-g/kg oral glucose load. However, using the intraperitoneal insulin infusion algorithm, excellent glycemic control (postprandial blood glucose of 9.1 ± 0.8 mmol/l at 70 min and 3.8 ± 0.3 mmol/l at 240 min, respectively) could be achieved without any associated delayed hyperinsulinemia or hypoglycemia. Glycemic excursion after 80-kcal/kg meal load was also controlled from 3.9 to 10.1 mmol/l. In addition, using the IP algorithm described n this study, excellent glycemic control after either an oral glucose load in the supine position or a meal load in the standing position could be achieved in diabetic dogs. It was not necessary to change the insulin infusion parameters in response to a positional change of the dogs.Our results confirm the feasibility of the intraperitoneal insulin infusion algorithm in vivo and that this algorithm can be superior to the subcutaneous insulin lispro infusion algorithm in the regulation of blood glucose.In conclusion, we developed the IP algorithm, designed for the AEP, as the summation of proportional and derivative actions in response to blood glucose concentration. With the AEP operated by this algorithm, blood glucose and insulin profiles during oral glucose load and meal load were successfully regulated in diabetic dogs. These data suggest the feasibility of glycemic control with closed-loop intraperitoneal insulin infusion in the treatment of human diabetes patients. Our results might encourage the development of the implantable AEP in the near future, which could provide optimal glycemic control of patients, especially those with type 1 diabetes. Less

研制人工内分泌胰腺的最终目的是实现长期严格的血糖调节。为了建立人工内分泌胰腺的生理胰岛素输送途径，腹腔内胰岛素输注可能是重要的。为此，我们尝试通过使用数学模型分析腹膜内规律胰岛素吸收的药代动力学来开发闭环腹膜内胰岛素输注算法。计算该算法的参数，以尽可能接近地模拟腹膜内胰岛素注射后的血浆胰岛素谱。为了评价该算法的适当性，我们尝试通过应用该算法在糖尿病犬中进行2 g/kg口服葡萄糖负荷或80 kcal/kg膳食负荷后的血糖控制。使用我们先前报道的皮下赖脯胰岛素输注算法，四氧嘧啶诱导的糖尿病犬表现出餐后高血糖和迟发性高胰岛素血症， ...更多信息 2-g/kg口服葡萄糖负荷后出现低血糖。然而，使用腹膜内胰岛素输注算法，可以实现极好的血糖控制（餐后70 min血糖为9.1 ± 0.8 mmol/l，餐后240 min血糖为3.8 ± 0.3 mmol/l），而没有任何相关的迟发性高胰岛素血症或低血糖。80 kcal/kg膳食负荷后的血糖波动也控制在3.9至10.1 mmol/l。此外，使用本研究中描述的IP算法，糖尿病犬在仰卧位口服葡萄糖负荷或站立位进餐负荷后均可实现良好的血糖控制。我们的结果证实了腹腔内胰岛素输注算法在体内的可行性，并且该算法在血糖调节方面上级皮下赖脯胰岛素输注算法。总之，我们开发了针对AEP设计的IP算法，作为响应于血糖浓度的比例和微分作用的总和。通过该算法操作的AEP，成功地调节了糖尿病犬在口服葡萄糖负荷和膳食负荷期间的血糖和胰岛素曲线。这些数据表明，闭环腹膜内胰岛素输注治疗人类糖尿病患者的血糖控制的可行性。我们的研究结果可能会鼓励在不久的将来开发植入式AEP，这可能会为患者提供最佳的血糖控制，特别是1型糖尿病患者。少