Micro Glucagon During Exercise in Type 1 Diabetes

This proof-of-principle study to assess effects of different doses (mini and micro) of subcutaneous glucagon analog Dasiglucagon (Zealand Pharma, Copenhagen, Denmark) on the change in blood glucose concentration during moderate-intensity exercise in people with T1D.

People with type 1 diabetes (T1D) are recommended to engage in regular exercise for a variety of health and fitness reasons. However, moderate-intensity exercise is associated with an increased risk of hypoglycaemia in people with T1D. Current guidelines are to reduce insulin dose and/or increase carbohydrate consumption in the context of the exercise bout. However, despite the many advances in insulin formulations and delivery devices, hypoglycaemia remains a significant risk. Mini-dose glucagon taken before an exercise bout has been shown to be an effective non-caloric strategy to prevent exercise-induced hypoglycaemia. However, even the reduced doses (150-200 µg) used in previous studies might still be rather high translating into potential side-effects (i.e. hyperglycaemia, gastrointestinal symptoms, etc.). Lower doses (below 100 µg, micro-glucagon) may be sufficiently effective to counteract hypoglycaemia risk associated with exercise and associated with better tolerance. Moreover, there is little information on the effects of subcutaneous glucagon on glycogen stores and changes in exercise metabolism. Greater understanding of exercise-associated metabolism following mini- and micro-dose glucagon using techniques such as magnetic resonance spectroscopy (MRS), continuous glucose monitoring (CGM), stable isotope tracers, and indirect calorimetry may result in novel approaches to improve blood glucose management in people with T1D. Utilising these techniques may also further our understanding of the optimal glucagon dosing (timing and amount) during exercise to manage hypoglycaemia and reduce the risk of adverse events. Proof-of-principle study to assess effects of different doses (mini and micro) of subcutaneous glucagon analog Dasiglucagon (Zealand Pharma, Copenhagen, Denmark) on the change in blood glucose concentration during moderate-intensity exercise in people with T1D. Secondly, to investigate exercise-metabolism following Dasiglucagon injection using 3 tesla magnetic resonance spectroscopy (MRS) and indirect calorimetry. Third, to assess participant experience of Dasiglucagon during exercise and the incidence of adverse events.

Eligibility Criteria:
Inclusion Criteria:

* T1D for \>1 year
* Male aged 18-45 years old
* HbA1c \<8.0% (64 mmol/mol) based on analysis from the central laboratory unit of Bern University Hospital
* Regular physical activity (defined as meeting 150 min moderate-intensity exercise per week)
* Using either continuous subcutaneous insulin infusion or multiple daily injections
* Written informed consent

Exclusion Criteria:

* Physical or psychological disease likely to interfere with the normal conduct of the study and interpretation of the results as judged by the investigator
* Current treatment with drugs known to interfere with metabolism e.g. systemic corticosteroids, statins, SGLT2 inhibitors, GLP1 agonists
* Relevant diabetic complications as judged by the investigator
* Body mass index 30 kg/m2
* Uncontrolled hypertension (\>180/100 mmHg)