Physical activity and hypoglycemia: can glucagon be the key to hypoglycemia prevention?

Physical activity and hypoglycemia: can glucagon be the key to hypoglycemia prevention?

What is glucagon?

Glucagon is a hormone that acts opposite to insulin and allows for sugar release from one’s own liver stores and into the bloodstream. 

Glucagon is specifically of interest when blood sugar is very low, hence why it is usually used as a severe hypoglycemia (low blood sugar requiring a third party assistance) emergency treatment.  (1)

Possible uses of Glucagon 

Currently glucagon is:

  1. Used to treat hypoglycemic episodes when an individual is unconscious and/or unable to consume fast acting sugars. This is the recommended indication and a 1mg dose is used. 
  2. Sometimes used outside of indication in far smaller doses during sick days, especially in children, when extreme nausea and vomiting make it impossible to eat.(2)

Glucagon was also studied as a substitute to sugar consumption to treat non-severe hypoglycemia (a blood glucose below 4.0 mmol/L not requiring a third party assistance) as there is no risk of over-correcting and thus avoiding major glycemia fluctuations within short periods of time. (3) Though a lot of patients living with T1D are looking for alternatives to a snack in such situations, this is not yet an available treatment option.
tute to sugar consumption to treat non-severe hypoglycemia (a blood glucose below 4.0 mmol/L not requiring a third party assistance) as there is no risk of over-correcting and thus avoiding major glycemia fluctuations within short periods of time. (3) Though a lot of patients living with T1D are looking for alternatives to a snack in such situations, this is not yet an available treatment option.

But that’s not all! 

A recently published study also looked at the possibility of using glucagon to prevent hypo when exercising. (4) Indeed exercise induced hypoglycemia has been identified as the main barrier limiting physical activity in patients living with type 1 diabetes. (5)

New study: can glucagon prevent physical activity induced hypo ?

This study by Rickels et al., included 15 adults who were on an insulin pump. They exercised, moderate intensity for 45 minutes, in a fasting condition.
In this trial, each participant had four exercise sessions, as follows:

1st: control conditions (No changes in insulin, carbs, and no glucagon) 

2nd: reduced pump basal insulin rate by 50%, 5 minutes before the exercise

3rd: participants had 20g of carbohydrates at the beginning of the exercise and 20 minutes into the session.

4th: participants were injected with 150 mg of glucagon 5 minutes before the exercise. This dose represent 15% of the dose used to treat a severe hypoglycemic episode

Exercise following glucagon injection had the least changes in blood sugar level from baseline during and after the exercise compared to control, basal insulin reduction, and carbohydrate intake.

They found that the reduction of the insulin basal rate by 50% 5 minutes before the exercise did not provide better blood sugar levels from the control session, and that carbohydrate intake tended to cause hyperglycemia in some participants. Indeed, another recent study suggested that reducing basal rate reduction need to be implemented more than 40 minutes before exercise initiation to have some impact to reduce hypoglycemic risk. (6) 

Authors concluded that a mini dose of glucagon (150 mg) may be an effective strategy for the prevention of exercise-induced hypoglycemia. 

Conclusion

While it might seem from these findings that glucagon may be the most effective way to prevent exercise-induced hypoglycemia; it is possible that earlier and larger insulin reduction as well as larger carbohydrate intake could also offer a reasonable protection. 
Additionally, the glucagon would need to be offered in a different formula than the current available powder for safer storage and longer shelf life. Other forms are in advanced stages of development but the cost might be a significant limitation. In addition the use of glucagon to prevent, rather than to treat, a hypoglycemic episode is currently used in some artificial pancreas versions that are not approved for use by Health Canada yet. (7)

References

  1. Yale JF, Paty B, Senior PA, Diabetes Canada Clinical Practice Guidelines Expert Committee. Hypoglycemia. Canadian journal of diabetes. 2018;42:108. doi:10.1016/j.jcjd.2017.10.010
  2. Haymond MW, Schreiner B. Mini-dose glucagon rescue for hypoglycemia in children with type 1 diabetes. Diabetes care. 2001;24(4):643-645.
  3. Haymond MW, Redondo MJ, McKay S, et al. Nonaqueous, mini-dose glucagon for treatment of mild hypoglycemia in adults with type 1 diabetes: a dose-seeking study. Diabetes care. 2016;39(3):465-468. doi:10.2337/dc15-2124
  4. Rickels MR, DuBose SN, Toschi E, et al. Mini-dose glucagon as a novel approach to prevent exercise-induced hypoglycemia in type 1 diabetes. Diabetes care. 2018;41(9):1909-1916. doi:10.2337/dc18-0051
  5. Brazeau AS, Rabasa-Lhoret R, Strychar I, Mircescu H. Barriers to physical activity among patients with type 1 diabetes. Diabetes care. 2008;31(11):2108-2109. doi:10.2337/dc08-0720
  6. Roy-Fleming A, Taleb N, Messier V, et al. Timing of insulin basal rate reduction to reduce hypoglycemia during late postprandial exercise in adults with type 1 diabetes using insulin pump therapy: a randomized crossover trial. Diabetes & metabolism. 2018;2018 Aug 27. doi:10.1016/j.diabet.2018.08.002
  7. Taleb N, Haidar A, Messier V, Gingras V, Legault L, Rabasa-Lhoret R. Glucagon in artificial pancreas systems: potential benefits and safety profile of future chronic use. Diabetes, obesity and metabolism. 2017;19(1):13-23. doi:10.1111/dom.12789