INTRAPERITONEAL INSULIN ADMINISTRATION IN DIABETES

在过去的五年里，胰岛素治疗的进展 依赖型糖尿病患者(I型)已将胰岛素输送到 腹膜间隙。从我们之前的研究来看，这有五个好处 胰岛素给药途径与静脉和皮下给药途径的比较 出现了：1)延长了胰岛素输送导管的通畅期(超过 五年)，2)门静脉胰岛素直接吸收(肝脏直接吸收 胰岛素治疗)，3)降低外周高胰岛素血症，4)迅速 腹膜内胰岛素的吸收，导致正常膳食胰岛素 以及5)血糖浓度的正常化和 糖化血红蛋白浓度。已经确立了优势 对于胰岛素的这一给药途径，我们现在建议扩大我们的 对特定的临床环境进行调查。这笔赠款分为 三个项目：1)检查患者的反应和胰岛素动力学 饮食、餐后和运动中的腹膜内注射胰岛素 糖尿病患者，2)胰岛素依赖型患者的长期随访(5年) 只接受过胰岛素治疗的糖尿病患者 经腹膜腔入路(这些患者均植入了我们的 一种遥控胰岛素输送泵，其胰岛素输送导管 终止于腹膜腔)，以及3)腹膜内胰岛素 在一组胰岛素依赖型糖尿病患者中分娩 对皮下注射胰岛素有抵抗力。安全地管理 后一类患者的腹膜腔内注射胰岛素，我们开发出一种 植入式FDA批准的皮下-腹膜下通路装置。这个 拟议的研究将仔细定义腹膜内注射的动力学。 胰岛素依赖型糖尿病患者的胰岛素吸收。长期的 对这些患者的好处可能是减少了两个微血管 糖尿病并发症(由于正常血糖所致)和 大血管-动脉粥样硬化并发症(由于正常 胰岛素配置文件)。视乎建议研究的结果， 腹膜腔内注射胰岛素可能成为首选胰岛素 为特定需要胰岛素的糖尿病患者提供的递送途径。

During the last five years, an advancement in the treatment of the insulin dependent diabetic patient (Type I) has been the delivery of insulin into the peritoneal space. From our previous studies, five advantages of this insulin delivery route compared to the intravenous and subcutaneous routes have emerged: 1) prolonged insulin delivery catheter patency (more than five years), 2) direct portal vein insulin absorption (direct hepatic insulinzation), 3) decreased peripheral hyperinsulinemia, 4) rapid absorption of intraperitioneal insulin, resulting in normal meal insulin profiles, and 5) normalization of the plasma glucose concentration and glycosylated hemoglobin concentration. Having established the advantages of this route of insulin delivery, we now propose to expand our investigation to specific clinical settings. The grant is divided into three projects: 1) examination of the response and insulin kinetics of intraperitoneally delivered insulin in the fed, postprandial and exercising diabetic patient, 2) long-term follow-up (five years) of insulin-dependent diabetic subjects who have received insulin exclusively by the intraperitoneal route (these patients have all been implanted with our remotely-controlled insulin delivery pump whose insulin delivery catheter terminates in the peritoneal space), and 3) intraperitoneal insulin delivery in a subgroup of insulin-dependent diabetic patients who are resistant to subcutaneous insulin delivery. To safely administer intraperitoneal insulin into these latter patients, we have developed an implantable FDA-approved subcutaneous-peritoneal access device. The proposed studies will carefully define the kinetics of intraperitoneal insulin absorption in insulin-dependent diabetic patients. The long-term benefits to these patients may be the reduction in both microvascular diabetic complications (as a result of normoglycemia) and a reduction in the macrovascular-atherosclerotic complications (as a result of normal insulin profiles). Depending upon the results of the proposed studies, the intraperitioneal delivery of insulin may become the preferred insulin delivery route for specific insulin-requiring diabetic patients.