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 NCT02882737Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00125-018-4807-8) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

Preference for Subcutaneously Administered Low-Dose Glucagon Versus Orally Administered Glucose for Treatment of Mild Hypoglycemia: A Prospective Survey Study

“…A recent outpatient study demonstrated that the plasma glucose response to 150 µg soluble glucagon was comparable to that of 40 g glucose taken as tabs [15]. However, several conditions may impair glucagon’s efficacy, i.e., low carbohydrate diets [16], exercise [17], ethanol intake [18], and hyperinsulinemia [19]. Therefore, if low-dose glucagon should be used in everyday treatment of mild hypoglycemia, a variable dosing regimen depending on these factors may be preferable as shown in a simulation study proposing an insulin-dependent glucagon dosing regimen for treatment of mild hypoglycemia [20].…”

Glucagon for hypoglycaemia treatment in type 1 diabetes

“…A study by Steineck et al demonstrated that the glucose response to low‐dose glucagon is not impaired after or during 45 min of moderate exercise; conversely, it is enhanced. Additionally, glucagon could be used immediately before starting exercise to minimize the subsequent glucose decline 42,96,97 . However, whether the glucose response to glucagon is preserved after prolonged exercise, with the risk of emptying liver glycogen depots, remains unclear.…”

Comparison of Continuous Glucose Monitoring Accuracy Between Abdominal and Upper Arm Insertion Sites

“…The inclusion criteria were as follows: age 18-70 years; body mass index 20-30 kg/m 2 ; HbA1c £8.5% (£69 mmol/mol); duration of type 1 diabetes ‡2 years; insulin pump treatment ‡1 year, selfreported hypoglycemia awareness, and use of carbohydrate counting and the insulin pump bolus calculator for all meals. Participants were excluded if unable to stop paracetamol usage during the study period, pregnant or breast-feeding, performing vigorous intense aerobic exercise more than 3 h per week due to a second study performed simultaneously, 5 or using medication besides insulin, influencing glucose metabolism.…”