Shimoda S, Nishida K, Sakakida M, Konno Y, Ichinose K, Uehara M, Nowak T, Shichiri M
Department of Metabolic Medicine, Kumamoto University School of Medicine, Japan.
Front Med Biol Eng. 1997;8(3):197-211.
Considering the management and safety of the insulin delivery route when a wearable artificial endocrine pancreas is applied to ambulatory diabetic patients on a long-term basis, we developed a s.c. insulin infusion algorithm by analyzing the dynamics of a s.c. injected short-acting insulin analog (Insulin Lispro) by a three-compartment 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 closely as possible. By applying this algorithm with regular insulin, diabetic patients showed a 2 h postprandial hyperglycemia and a delayed hyperinsulinemia, followed by hypoglycemic episodes 4-5 h after oral glucose load, just as observed in the computer simulation study. However, using Insulin Lispro, a near-physiological glycemic control (postprandial blood glucose of 153.1 +/- 8.3 mg/100 ml at 60 min and 90.3 +/- 7.1 mg/100 ml at 180 min, respectively) could be achieved without showing any delayed hyperinsulinemia or hypoglycemia. Daily glycemic excursions were also controlled near-physiologically and although the daily insulin requirement (731.7 +/- 160.5 mU/kg/day) was slightly higher, it was not significantly different from that with i.v. insulin infusion (622.3 +/- 142.6 mU/kg/day). These results indicate that the application of s.c. insulin infusion algorithm with Insulin Lispro is feasible for long-term glycemic control with a wearable artificial endocrine pancreas in ambulatory diabetic patients.
考虑到长期将可穿戴式人工内分泌胰腺应用于门诊糖尿病患者时胰岛素给药途径的管理和安全性，我们通过三室模型分析皮下注射短效胰岛素类似物（赖脯胰岛素）的动力学，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一种传递函数，在比例和微分作用方面对血糖浓度具有一阶延迟。计算该算法的参数以尽可能模拟生理血浆胰岛素曲线。通过将该算法与常规胰岛素一起应用，糖尿病患者出现了餐后2小时高血糖和延迟的高胰岛素血症，随后在口服葡萄糖负荷后4 - 5小时出现低血糖发作，就像在计算机模拟研究中观察到的那样。然而，使用赖脯胰岛素，可以实现接近生理的血糖控制（餐后60分钟血糖为153.1±8.3mg/100ml，180分钟时为90.3±7.1mg/100ml），且未出现任何延迟的高胰岛素血症或低血糖。每日血糖波动也得到了接近生理的控制，尽管每日胰岛素需求量（731.7±160.5mU/kg/天）略高，但与静脉输注胰岛素（622.3±142.6mU/kg/天）相比无显著差异。这些结果表明，在门诊糖尿病患者中，将皮下胰岛素输注算法与赖脯胰岛素一起应用于可穿戴式人工内分泌胰腺进行长期血糖控制是可行的。
