Closed-loop system in the management of diabetes: past, present, and future.

Intensive insulin therapy (IIT) has been shown to reduce micro- and macrovascular complications in patients with type 1 diabetes mellitus (T1DM). However, IIT is associated with a significant increase in severe hypoglycemic events, resulting in increased morbidity and mortality. Optimization of glycemic control without hypoglycemia (especially nocturnal) should be the next major goal for subjects on insulin treatment. The use of insulin pumps along with continuous glucose monitors (CGMs) has made it easier but requires significant resources and patient education. Research is ongoing to close the loop by integrating the pump and the CGM using different algorithms. The currently available closed-loop system is the threshold suspend. Steps needed to achieve a near-perfect closed-loop are (1) a control-to-range system that will reduce the incidence and/or severity of hyper- and/or hypoglycemia by adjusting the insulin dose and (2) a control-to-target system, a fully automated or hybrid system that sets target glucose levels to individual needs and maintains glucose levels throughout the day using insulin (unihormonal) alone or with other hormones such as glucagon or possibly pramlintide (bihormonal). Future research is also focusing on better insulin delivery devices (pumps), more accurate CGMs, better predictive algorithms, and ultra-rapid-acting insulin analogs to make the closed-loop system as physiological as possible.