Controlled drug delivery in the treatment of diabetes mellitus.Crit Rev Ther Drug Carrier Syst. 1985; 1(3):189-280.CR
Diabetes not only requires correction of an insulin deficiency but it also demands adequate insulin delivery. A short historical review is given over the first 60 years of insulin treatment, where emphasis was mainly on the correction of insulin deficiency. Despite concerted efforts, metabolic results were often poor, and there was a high incidence of late complications, which will be described briefly. A major aim of new treatment approaches, which emphasizes better routes of insulin delivery, is the prevention or reversal of these late complications. Closed-loop systems are infusion systems located outside the body which deliver insulin according to glucose values that are measured continuously. The state of the art for such systems will be described with examples of clinical applications and results. These systems aid and stimulate research, but offer no long-term application for treatment. Open-loop systems are portable, both external and implantable, and lack an accurate glucose sensor so that the loop can be closed. A number of insulin delivery systems have been developed in this category ranging from highly complex, fully implantable units, programable from outside, to simple basal-rate infusion pumps. Various pumps are designed to be used with varying delivery routes, and the evaluation of different routes will be a vital topic in this article. Pros and cons of the intravenous, intraperitoneal, and subcutaneous routes will be discussed, with supporting research referenced. Clinical experience will be cited for both the complex and the simple infusion systems. Other topics to be covered include feasibility of long-term treatment, complications of this new treatment approach, guidelines for patient instruction and supervision, requirements for treatment of large patient groups with pumps in a modern diabetes center, requirements for the physician, the influence of improved metabolic control on late complications (prevention or regression), the possibility for a portable closed-loop system, and future outlook. The primary author is the founder of an international study group on diabetes treatment with implantable insulin delivery devices. The common goals of this study group will also be presented. Special emphasis will be placed on a differentiated approach to treatment of Type I and Type II diabetes with a family of devices. Clinical work and results from a large patient group will be included throughout.