Automated closed-loop control of diabetes: the artificial pancreas.

The incidence of Diabetes Mellitus is on the rise worldwide, which exerts enormous health toll on the population and enormous pressure on the healthcare systems. Now, almost hundred years after the discovery of insulin in 1921, the optimization problem of diabetes is well formulated as maintenance of strict glycemic control without increasing the risk for hypoglycemia. External insulin administration is mandatory for people with type 1 diabetes; various medications, as well as basal and prandial insulin, are included in the daily treatment of type 2 diabetes. This review follows the development of the Diabetes Technology field which, since the 1970s, progressed remarkably through continuous subcutaneous insulin infusion (CSII), mathematical models and computer simulation of the human metabolic system, real-time continuous glucose monitoring (CGM), and control algorithms driving closed-loop control systems known as the "artificial pancreas" (AP). All of these developments included significant engineering advances and substantial bioelectronics progress in the sensing of blood glucose levels, insulin delivery, and control design. The key technologies that enabled contemporary AP systems are CSII and CGM, both of which became available and sufficiently portable in the beginning of this century. This powered the quest for wearable home-use AP, which is now under way with prototypes tested in outpatient studies during the past 6 years. Pivotal trials of new AP technologies are ongoing, and the first hybrid closed-loop system has been approved by the FDA for clinical use. Thus, the closed-loop AP is well on its way to become the digital-age treatment of diabetes.