INTRAPERITONEAL INSULIN ADMINISTRATION IN DIABETES

在过去的五年里，胰岛素治疗的进展 依赖性糖尿病患者（I型）已经将胰岛素递送至 腹膜腔 从我们以前的研究来看，这五个优点 胰岛素给药途径与静脉和皮下途径相比 已经出现：1）延长的胰岛素输送导管通畅（超过 5年），2）直接门静脉胰岛素吸收（直接肝 胰岛素），3）外周高胰岛素血症减少，4）快速 腹膜内胰岛素的吸收，导致正常餐时胰岛素 5）血浆葡萄糖浓度的标准化， 糖化血红蛋白浓度。 在确立了优势之后， 在这种胰岛素输送途径中，我们现在建议扩大我们的 对特定临床环境的研究。 补助金分为 三个项目：1）检查的反应和胰岛素动力学， 在进食、餐后和运动中腹膜内递送胰岛素 糖尿病患者，2）长期随访（5年）胰岛素依赖性 糖尿病受试者仅接受胰岛素治疗， 腹膜内途径（这些患者均植入了我们的 其胰岛素输送导管 终止于腹膜间隙），和3）腹膜内胰岛素 在胰岛素依赖型糖尿病患者亚组中的递送， 抵抗皮下胰岛素输送。 为了安全地管理 腹膜内注射胰岛素，我们已经开发了一种 FDA批准的可植入皮下腹膜通路装置。 的 建议的研究将仔细定义腹膜内给药的动力学， 胰岛素依赖型糖尿病患者的胰岛素吸收。 长期 对这些患者的益处可能是减少微血管和 糖尿病并发症（由于血糖正常）和减少 大血管动脉粥样硬化并发症（由于正常的 胰岛素谱）。 根据拟议研究的结果， 胰岛素的腹膜内递送可能成为优选的胰岛素 给药途径，用于需要胰岛素的特定糖尿病患者。

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.