Artificial Pancreas: Past, Present, Future

The artificial pancreas (AP), known as closed-loop control of blood glucose in diabetes, is a system combining a glucose sensor, a control algorithm, and an insulin infusion device. AP developments can be traced back 50 years to when the possibility for external blood glucose regulation was established by studies in individuals with type 1 diabetes using intravenous glucose measurement and infusion of insulin and glucose. After the pioneering work by Kadish (1) in 1964, expectations for effectively closing the loop were inspired by the nearly simultaneous work of five teams reporting closed-loop control results between 1974 and 1978: Albisser et al. (2), Pfeiffer et al. (3), Mirouze et al. (4), Kraegen et al. (5), and Shichiri et al. (6). In 1977, one of these realizations (3) resulted in the first commercial device—the Biostator (7; Fig. 1), followed by another inpatient system, the Nikkiso STG-22 Blood Glucose Controller, now in use in Japan (8). FIG. 1. The Biostator (courtesy of William Clarke, University of Virginia). Although the intravenous route of glucose sensing and insulin infusion is unsuitable for outpatient use, these devices proved the feasibility of external glucose control and stimulated further technology development. Figure 2 presents key milestones in the timeline of AP progress. FIG. 2. Key milestones in the timeline of AP progress. EU, Europe; IP, intraperitoneal; NIH, National Institutes of Health; SC, subcutaneous. In 1979, landmark studies by Pickup et al. (9) and Tamborlane et al. (10) showed that the subcutaneous route was feasible for continuous insulin delivery. Three years later, Shichiri et al. (11) tested a prototype of a wearable AP, which was further developed in subsequent studies (12,13). In the late 1980s, an implantable system was introduced using intravenous glucose sensing and intraperitoneal insulin infusion (14). This technology was further developed, leading to clinical trials and …