Finding balance: causes of hypoglycemia with a glucagon/insulin pump system

This study examined the factors involved in the successful control of hypoglycemia with an insulin-glucagon pump.

Hypoglycemia (dangerously low blood glucose [sugar] levels) is a common side effect of insulin therapy for type 1 diabetes mellitus. Hypoglycemia can occur when there is too much insulin at any one time. The treatment for this is an injection of glucagon, a man-made version of a hormone normally produced by the pancreas, which raises the level of blood glucose. However, glucagon is only used as a treatment, and as yet cannot be used to prevent hypoglycemia.

Newer insulin pump systems, which deliver insulin directly through a flexible tube through the skin, can suspend insulin delivery in anticipation of hypoglycemia, but this is not always successful. Pumps are now being developed that deliver both insulin and glucagon. A main concern with this type of system is maintaining a balance between insulin and glucagon so that blood glucose levels remain steady.

The current study examined the factors involved in a successful insulin/glucagon pump system in type 1 diabetes. This analysis examined four previous studies including 48 subjects. All patients used pumps delivering both insulin and glucagon. Depending on the study, blood glucose levels were measured from every 10 minutes to up to every 2 hours.

Glucagon was able to prevent hypoglycemia in 78% of instances where delivery was needed, and failed 16% of the time. Hypoglycemia, or a glucagon failure, were found to be associated with three factors. Patients who experienced a rapid decrease in glucose were 2.7 times more likely to experience a glucagon failure than patients with a slower decrease. Patients with lower baseline glucose levels (levels at the time glucagon is released) were 3 times more likely to experience a glucagon failure. Patients with higher insulin levels at the time of glucagon release had a 14% increase in the risk of glucagon failure and hypoglycemia.

This study concluded that the occurrence of hypoglycemia in patients using a two-hormone pump system is associated with low initial blood glucose levels, rapidly decreasing glucose levels, or high insulin levels at the time of glucagon delivery. Careful tuning of the two-hormone pump is necessary to avoid these failures.