Pathway to Artificial Pancreas Systems Revisited: Moving Downstream

Abstract

Artificial pancreas (AP) systems, a long-sought quest to replicate mechanically islet physiology that is lost in diabetes, are reaching the clinic, and the potential of automating insulin delivery is about to be realized. Significant progress has been made, and the safety and feasibility of AP systems have been demonstrated in the clinical research center and more recently in outpatient "real-world" environments. An iterative road map to AP system development has guided AP research since 2009, but progress in the field indicates that it needs updating. While it is now clear that AP systems are technically feasible, it remains much less certain that they will be widely adopted by clinicians and patients. Ultimately, the true success of AP systems will be defined by successful integration into the diabetes health care system and by the ultimate metric: improved diabetes outcomes.An electromechanical approach to improve glycemic control and quality of life for people with diabetesdan artificial pancreas (AP) (or an automated insulin-delivery system or bionic pancreas)dhas been a long-sought technological goal of diabetes researchers (1). However, a number of significant challenges needed to be overcome to deliver an AP system to people with diabetes. The past 10 years have seen many of these challenges addressed, and recent studies have demonstrated compelling safety and efficacy of the prototype systems (2). Technical feasibility is only a step toward declaring victory. Research and development efforts will continue to improve upon first-generation AP systems. But, it is clear that resources will need to be deployed to address clinical adoption challengesdincluding device usability and reimbursement.Research and development efforts over the past 10 years have addressed a number of the critical issues facing AP development, and recent studies again signal a move to a new phase and a call for a new road map to AP systems. A number of groups have demonstrated proof of concept with a variety of algorithmic approaches and closed-loop strategies and the data are compelling. In a Bench to Clinic narrative, Cefalu and Tamborlane (3) dive much deeper than this Perspective intends into the "how" of AP systems. They note quite astutely that "it is not the journey, but the destination that matters" (3).It may come as a surprise to many clinicians, but a small and growing group of lay, "do-it-yourself," technically savvy people with diabetes or loved ones of people with diabetes has been using semiautomated closed-loop systems at home for well over 2 years with impressive results (4-6). These systems, similar to systems being studied in academic studies, combine off-the-shelf insulin pumps and continuous glucose monitors with control algorithms (computer software that interprets glucose information and drives the dosing of insulin) powered by cell phone devices. The results from academia and these anecdotal reports are harbingers of a JDRF, New York, NY

Diabetes Technology and Therapy in the Pediatric Age Group

“…The use of a PLGS system represents the second step in the artificial pancreas roadmap (21). The first step, threshold suspension of insulin with a low CGM glucose, has been commercially available since 2009 in many countries and since 2013 in the United States.…”

Progress in Diabetes Technology: Developments in Insulin Pumps, Continuous Glucose Monitors, and Progress towards the Artificial Pancreas

“…Data exist on all steps of the 2009 roadmap summarized in this section, which demonstrate the feasibility of each. 46–55 Therefore, an updated roadmap has been introduced by Kowalski 55 to emphasize a bifurcated pathway to insulin only and bihormonal insulin systems. The Food and Drug Administration also has issued updated guidelines specifically for artificial pancreas development with an attempt to achieve “the least burdensome approach” toward artificial pancreas testing and approval.…”

Towards a Verified Artificial Pancreas: Challenges and Solutions for Runtime Verification

“…Table 1 shows the original stage wise development for the overall AP concept. A recently revised pathway acknowledges that all stages are [26,25] Use glucagon and insulin to achieve bidirectional control currently technologically feasible and classifies insulin delivery beyond stage 3 simply as "insulin-only" control and "multihormonal" control [39]. The first (and simplest) stage simply shuts off the pump when the blood glucose level is sensed below a widely accepted threshold for hypoglycemia.…”