Closed-loop insulin delivery for treatment of type 1 diabetes

Type 1 diabetes is a chronic disease caused by T-cell-mediated autoimmune destruction of the pancreatic β cells in genetically predisposed individuals [1]. Insulin discovery in the early 1920s transformed diabetes from a uniformly fatal condition into a disease requiring life-long insulin-replacement therapy. The Diabetes Control and Complication Trial linked tight control of glucose to prevention of long-term diabetes-related vascular complications [2]. Intensification of insulin therapy has become an essential treatment method, but it has been hindered by an increased risk of hypoglycemia [3]. Severe hypoglycemia may lead to seizures or loss of consciousness, and can be life-threatening. Fear of hypoglycemia by patients and caregivers may adversely affect patients' quality of life and psychological well-being [4], and may result in 'over-compensatory' behaviors such as overeating or taking less insulin [5].Technological innovations continue to benefit the management of type 1 diabetes. Novel rapid and long-acting insulin analogs and more physiological insulin-delivery systems including smart insulin pumps are increasingly being used. Glucose monitoring is evolving, leading to greater availability of subcutaneous continuous monitors, which provide frequent, real-time, and minimally invasive glucose measurements [6]. Sensor-augmented pump therapy increases convenience by integrating continuous glucose monitoring with an insulin pump. Despite these advances, the current best management of glucose control is still inadequate. Sensor-augmented pump therapy is unable to prevent severe hypoglycemia, with an incidence in patients using such therapy similar to that observed in those using conventional therapy [7]. Glucose levels in adults are above the target glucose level of 10 mmol/l for more than 8 hours per day, with even higher rates observed in the pediatric and adolescent populations [8]. Automated systems modulating insulin delivery according to sensor glucose leve