In a nutshell

This review assessed the development and use of an artificial pancreas (a bi-hormonal closed loop system) in the management of type 1 diabetes mellitus.

Some background

A normally functioning pancreas releases both insulin and the hormone glucagon. Glucagon acts in opposition to insulin, raising blood glucose levels when they become too low. Therefore, maintaining optimal blood glucose levels in a healthy individual depends on a delicate balance between insulin and glucagon.

Patients with type 1 diabetes are unable to produce the hormone insulin, needed to utilize glucose taken in from food. This can lead to high levels of glucose in the blood stream, which can damage nerves, blood vessels and various organs. However, since glucagon secretion is also impaired in the diabetic pancreas, the use of insulin injections alone in the management of diabetes can cause hypoglycemia (dangerously low blood glucose levels), a serious complication which may be life threatening.

New therapies for diabetes include a closed-loop system, which constantly monitors blood glucose levels and automatically delivers insulin as needed. Closed-loop systems have reduced the incidence of hypoglycemia, however management over the disease is still far from optimal. A new avenue of research in recent years has been the development of a bi-hormonal closed loop system which can deliver both insulin and glucagon as needed. In essence, this bi-hormonal closed-loop system is the equivalent of an external artificial pancreas. The current review analyzed the use of bi-hormonal systems in recently conducted clinical trials.

Methods & findings

All studies comparing the delivery of insulin alone to bi-hormonal systems showed that the addition of glucagon to therapy led to significantly fewer episodes of hypoglycemia.

One study comparing a bi-hormonal closed loop system to daily insulin injections found that only 7% of patients receiving both insulin and glucagon experienced hypoglycemia at some point during treatment, compared to 53% of patients receiving insulin injections. For the few patients in the study who did experience hypoglycemia while using a bi-hormonal closed-loop system, it was determined that the sensors overestimated blood glucose levels, leading to a delay in the release of glucagon. Researchers concluded that improvements in sensor accuracy could decrease the incidence hypoglycemic events even further, if not completely.

A small study assessing the effectively of bi-hormonal closed-loop systems during exercise, concluded that bi-hormonal systems are safe and effective at preventing hypoglycemia during physical activity.

The major obstacle in the development of a working artificial pancreas however is the formulation of glucagon. Current forms of glucagon thicken into a gel-like substance within days of being exposed to water, which renders the hormone unusable and clogs the drug-pump used to deliver it. New stable solutions of glucagon must be developed before bi-hormonal systems can be approved for general use.

The bottom line

This review concluded that bi-hormonal closed-loop systems are developing rapidly and may soon enter common use. Bi-hormonal systems seem to be more effective at preventing hypoglycemia and maintaining optimal blood glucose levels than insulin alone.

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