Saudek C D
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Endocrinol Metab Clin North Am. 1997 Sep;26(3):599-610. doi: 10.1016/s0889-8529(05)70269-3.
Despite its widespread use, much is wrong with conventional subcutaneous insulin injection. It is more-or-less painful and inconvenient; it delivers insulin slowly with highly inconsistent pharmacokinetics into the peripheral venous system rather than directly to the liver via the portal vein; and, once delivered into the skin, it cannot be "turned off". This review has focused on novel alternative approaches to insulin delivery. The clinically available insulin delivery devices, such as pen injectors and external insulin pumps, are probably underutilized. Pen injectors offer convenience, whereas external pumps offer a basal/bolus approach to insulin delivery unlike that achieved by injections. Of the approaches currently under development, IPPs are closet to general availability. They have been extremely popular in more than 600 patients worldwide, however, an insulin problem has delayed application for their PMA in the United States. Feasibility studies of inhaled insulin, nasal insulin, and oral insulin have produced interesting preliminary findings, with pulmonary delivery for meal coverage with short-acting insulin having perhaps the brightest prospects. Encapsulated islets and biohybrid systems that place live islets into an implanted device are in earlier stages of development. Closing the loop with a continuous glucose sensor will be the only way to achieve truly normal blood glucose homeostasis by directing insulin delivery automatically on demand. Glucose sensors would have many other clinical applications in diabetes management in addition to driving a mechanical delivery system. However, the development of glucose sensing devices has been a formidable technical challenge. Based on an evaluation of current technologic development, glucose oxidase-based, needle-type sensors may become available within the next few years. Clinicians, the research community, and persons with diabetes can join in rejecting the notion that standard regimens of insulin injection do not need to be improved. If there is adequate incentive to continue a broad-based research effort into novel approaches to insulin delivery, the quality of life of persons with diabetes can be improved in the not too distant future.
尽管传统皮下胰岛素注射被广泛使用，但它存在诸多问题。它或多或少会带来疼痛且不方便；它将胰岛素缓慢地输送到外周静脉系统，药代动力学极不稳定，而非通过门静脉直接输送到肝脏；而且，一旦注入皮肤，就无法“关闭”。本综述聚焦于胰岛素递送的新型替代方法。临床上可用的胰岛素递送装置，如笔式注射器和外部胰岛素泵，可能未得到充分利用。笔式注射器提供了便利，而外部泵提供了基础/大剂量胰岛素递送方法，这与注射方式不同。在目前正在研发的方法中，胰岛素植入泵最接近普遍可用。它们在全球600多名患者中非常受欢迎，然而，一个胰岛素问题推迟了其在美国的上市前批准申请。吸入胰岛素、鼻用胰岛素和口服胰岛素的可行性研究已产生了有趣的初步结果，其中使用短效胰岛素进行肺部给药以覆盖餐时血糖可能前景最为光明。封装胰岛和将活胰岛置于植入装置中的生物混合系统尚处于早期开发阶段。通过连续葡萄糖传感器实现闭环，将是通过按需自动指导胰岛素递送从而实现真正正常血糖稳态的唯一途径。除了驱动机械递送系统外，葡萄糖传感器在糖尿病管理中还有许多其他临床应用。然而，葡萄糖传感装置的开发一直是一项艰巨的技术挑战。基于对当前技术发展的评估，基于葡萄糖氧化酶的针型传感器可能在未来几年内问世。临床医生、研究界和糖尿病患者可以共同摒弃标准胰岛素注射方案无需改进的观念。如果有足够的动力继续对胰岛素递送新方法进行广泛的研究努力，那么在不久的将来，糖尿病患者的生活质量将会得到改善。
