Preserved glucose response to low-dose glucagon after exercise in insulin-pump-treated individuals with type 1 diabetes: a randomised crossover study

Abstract

Aims/hypothesis: This study aimed to compare the increase in plasma glucose after a subcutaneous injection of 200 μg glucagon given after 45 min of cycling with resting (study 1) and to investigate the effects of glucagon when injected before compared with after 45 min of cycling (study 2). We hypothesised that: (1) the glucose response to glucagon would be similar after cycling and resting; and (2) giving glucagon before the activity would prevent the exercise-induced fall in blood glucose during exercise and for 2 h afterwards. Methods: Fourteen insulin-pump-treated individuals with type 1 diabetes completed three visits in a randomised, placebo-controlled, participant-blinded crossover study. They were allocated by sealed envelopes. Baseline values were (mean and range): HbA 1c 54 mmol/mol (43–65 mmol/mol) or 7.1% (6.1–8.1%); age 45 years (23–66 years); BMI 26 kg/m 2 (21–30 kg/m 2 ); and diabetes duration 26 years (8–51 years). At each visit, participants consumed a standardised breakfast 2 h prior to 45 min of cycling or resting. A subcutaneous injection of 200 μg glucagon was given before or after cycling or after resting. The glucose response to glucagon was compared after cycling vs resting (study 1) and before vs after cycling (study 2). Results: The glucose response to glucagon was higher after cycling compared with after resting (mean ± SD incremental peak: 2.6 ± 1.7 vs 1.8 ± 2.0 mmol/l, p = 0.02). As expected, plasma glucose decreased during cycling (−3.1 ± 2.8 mmol/l) but less so when glucagon was given before cycling (−0.9 ± 2.8 mmol/l, p = 0.002). The number of individuals reaching glucose values ≤3.9 mmol/l was the same on the 3 days. Conclusions/interpretation: Moderate cycling for 45 min did not impair the glucose response to glucagon compared with the glucose response after resting. The glucose fall during cycling was diminished by a pre-exercise injection of 200 μg glucagon; however, no significant difference was seen in the number of events of hypoglycaemia. Trial registration: Clinicaltrials.gov NCT02882737 Funding: The study was funded by the Danish Diabetes Academy founded by Novo Nordisk foundation and by an unrestricted grant from Zealand Pharma.