Closed-loop insulin delivery in type 1 diabetes

Abstract

Advances in diabetes technology have led to significant improvements in the quality of life and care received by individuals with diabetes. Despite this, achieving tight glycemic control through intensive insulin therapy and modern insulin regimens is challenging because of the barrier of hypoglycemia, the most feared complication of insulin therapy as reported by patients, caregivers, and physicians. This article outlines the individual components of the closed-loop system together with the existing clinical evidence. The artificial pancreas prototypes currently used in clinical studies are reviewed as well as obstacles and limitations facing the technology.

Figure 1

Illustration of a closed-loop system comprising of a glucose sensor (rectangle on the left-hand side of the abdomen), an insulin pump (device in the pocket connected to patient via an infusion-set) and a mobile sized device containing the control algorithm (in patient’s hand). Each component communicates with each other wirelessly. (From Hovorka R. Closed-loop insulin delivery: from bench to clinical practise. Nat. Rev.Endocrinol 2011; 7: 385–395)

Figure 2

Examples of continuous glucose monitoring devices; the Dexcom^™ SEVEN® PLUS (above), and the Freestyle Navigator® (below).

Figure 3

A sensor augmented insulin pump; the MiniMed Paradigm Veo® integrated with the Enlite® continuous glucose sensor.

Figure 4

A study participant displaying the Florence closed-loop insulin delivery system, consisting of a handheld device (Companion) which receives and displays glucose value data from the Freestyle Navigator Transmitter, communicating with the Control Algorithm Device (CAD) and controlling the subcutaneous insulin pump.

Figure 5

The three panels illustrate glucose levels and insulin delivery profiles observed during a 36 hour closed-loop study in a young subject. The bold line shows the continuous subcutaneous glucose trace and the black square indicate reference plasma glucose values (not used to determine the insulin delivery but shown to demonstrate deviation between sensor and plasma glucose levels). Insulin infusion rates during closed-loop delivery are denoted by the grey line. Vertical arrows indicate meals and snacks (light grey arrow) and insulin boluses (dark grey arrow). Carbohydrate contents of the meal/snack and insulin doses are also shown. Horizontal dashed lines illustrate the target range of 90 to 180 mg/dl (3.9 to 10mmol/L).