Glucagon is absorbed from the rectum but does not hasten recovery from hypoglycaemia in patients with type 1 diabetes

Abstract

Aims: A failure to secrete glucagon during hypoglycaemia is near universal in patients with type 1 diabetes 5 years after disease onset and may contribute to delayed counter-regulation during hypoglycaemia. Rectal glucagon delivery may assist glucose recovery following insulin-induced hypoglycaemia in such patients and has not been previously studied.

Methods: Six male patients (age 21-38 years) with type 1 diabetes (median duration 10 years) without microvascular complications, were studied supine after an overnight fast on two separate occasions at least 14 days apart. After omission of their usual morning insulin and 45 min rest, hypoglycaemia was induced by an intravenous insulin infusion which was terminated when capillary glucose concentration reached 2.5 mmol l(-1). Subjects were randomized to insert a rectal suppository containing 100 mg indomethacin alone (placebo) or 100 mg indomethacin plus 1 mg glucagon at the hypoglycaemic reaction. Serial measurements were made for 120 min.

Results: In the two groups, mean (SD) plasma glucose concentrations fell to a similar nadir of 1.8 (0.7) mmol l(-1) (placebo) and 2.1 (1.2) mmol l(-1) (glucagon). Peak plasma glucagon following hypoglycaemia was higher in the glucagon group; 176 (32) ng l(-1)vs. 99 (22) ng l(-1) after placebo (P = 0.006). However, the glucose recovery rate over 120 min after hypoglycaemia did not differ significantly.

Conclusions: Our results provide evidence for the absorption of glucagon from the rectum. They also indicate that 1 mg does not constitute a useful mode of therapy to hasten recovery from hypoglycaemia in patients with type 1 diabetes.

Figure 1

The effects of a rectal suppository containing 100 mg indomethacin alone (placebo x) or 100 mg indomethacin and 0.1 mg (open circles), 0.5 mg (open triangles) or 1 mg (open squares) glucagon on mean (95% CI) fasting plasma glucose (A), glucagon (B), and insulin (C) in 10 healthy volunteers. Plasma glucose rose in a dose dependent manner in response to increasing doses of glucagon. Plasma glucagon showed a significant rise from baseline after the suppository containing 1 mg glucagon. Insulin concentration rose after glucagon insertion but there were no significant dose dependent effects

Figure 2

Mean (95% CI) plasma glucose (A) and insulin (B) concentrations following the administration of an intravenous infusion of insulin in six fasting male patients with type 1 diabetes studied on two separate occasions. Patients received a suppository of 100 mg indomethacin alone (placebo ×, solid lines) or 100 mg indomethacin and 1 mg glucagon (open circles, dotted lines) at the hypoglycaemic reaction (↓). The nadir of glucose and peak insulin concentration at the hypoglycaemic reaction did not differ on the two study days, and the recovery from hypoglycaemia was no different after placebo or glucagon

Figure 3

Mean (95% CI) plasma glucagon (A), adrenaline (B) and noradrenaline (C) concentrations following the administration of an intravenous infusion of insulin in six fasting male patients with type 1 diabetes studied on two separate occasions. Patients received a suppository of 100 mg indomethacin alone or 100 mg indomethacin and 1 mg glucagon at the hypoglycaemic reaction (↓). Glucagon concentrations rose significantly after the glucagon suppository was inserted and remained elevated for 90 min but did not change after placebo. Peak catecholamine responses to hypoglycaemia were no different on the two study days