Closed-loop insulin delivery for treatment of type 1 diabetes

Abstract

Type 1 diabetes is one of the most common endocrine problems in childhood and adolescence, and remains a serious chronic disorder with increased morbidity and mortality, and reduced quality of life. Technological innovations positively affect the management of type 1 diabetes. Closed-loop insulin delivery (artificial pancreas) is a recent medical innovation, aiming to reduce the risk of hypoglycemia while achieving tight control of glucose. Characterized by real-time glucose-responsive insulin administration, closed-loop systems combine glucose-sensing and insulin-delivery components. In the most viable and researched configuration, a disposable sensor measures interstitial glucose levels, which are fed into a control algorithm controlling delivery of a rapid-acting insulin analog into the subcutaneous tissue by an insulin pump. Research progress builds on an increasing use of insulin pumps and availability of glucose monitors. We review the current status of insulin delivery, focusing on clinical evaluations of closed-loop systems. Future goals are outlined, and benefits and limitations of closed-loop therapy contrasted. The clinical utility of these systems is constrained by inaccuracies in glucose sensing, inter- and intra-patient variability, and delays due to absorption of insulin from the subcutaneous tissue, all of which are being gradually addressed.

Figure 1

An illustrative representation of a closed-loop insulin delivery system. (A) A sensor (black rectangle) transmits information about interstitial glucose levels to a handheld device about the size of a cellphone (red box) which holds a control algorithm and interacts with the user. An insulin pump (blue box in the pocket) delivers a rapid-acting insulin analog subcutaneously. Insulin delivery is modulated by the control algorithm. The communication between the system components is wireless. The control algorithm can also reside within the insulin pump. (Adapted from Hovorka [12]). (B) The closed loop replicates the physiological feedback normally provided by the β-cell.

Figure 2

Distribution of plasma glucose levels after midnight in young people and adults during (top panel) closed-loop and (bottom panel) conventional insulin-pump therapy (continuous subcutaneous insulin infusion (CSII)). Vertical dashed lines indicate the threshold of significant hypoglycemia (3.0 mmol/l) and the target glucose range of 3.91 to 8.0 mmol/l. Values at the top denote the percentage of plasma glucose values within the respective glucose ranges (reproduced with permission from Kumareswaran et al. [60]).