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

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⁻¹vs. 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.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Patients with type 1 diabetes experience recurrent hypoglycaemia and have abnormal glucose counter regulatory responses with a failure to secrete glucagon. It is unknown if rectal glucagon is absorbed and what effect this may have on counter regulation from hypoglycaemia.

WHAT THIS STUDY ADDS

• A rectal suppository of glucagon results in a rise in plasma glucagon with metabolic effects in normal subjects. Similarly rectal glucagon results in a rise in plasma glucagon in patients with type 1 diabetes, but 1 mg does not improve recovery rates from experimental hypoglycaemia when compared with placebo.
• Larger doses of glucagon per rectum may provide pharmacological circulating concentrations with resulting therapeutic benefit during recovery from hypoglycaemia and deserves further study.