Mini-Dose Glucagon as a Novel Approach to Prevent Exercise-Induced Hypoglycemia in Type 1 Diabetes

Patients with type 1 diabetes who do aerobic exercise often experience a drop in blood glucose concentration that can result in hypoglycemia. Current approaches to prevent exercise-induced hypoglycemia include reduction in insulin dose or ingestion of carbohydrates, but these strategies may still result in hypoglycemia or hyperglycemia. We sought to determine whether mini-dose glucagon (MDG) given subcutaneously before exercise could prevent subsequent glucose lowering and to compare the glycemic response to current approaches for mitigating exercise-associated hypoglycemia.

We conducted a four-session, randomized crossover trial involving 15 adults with type 1 diabetes treated with continuous subcutaneous insulin infusion who exercised fasting in the morning at ∼55% VO_2max for 45 min under conditions of no intervention (control), 50% basal insulin reduction, 40-g oral glucose tablets, or 150-μg subcutaneous glucagon (MDG).

During exercise and early recovery from exercise, plasma glucose increased slightly with MDG compared with a decrease with control and insulin reduction and a greater increase with glucose tablets (P < 0.001). Insulin levels were not different among sessions, whereas glucagon increased with MDG administration (P < 0.001). Hypoglycemia (plasma glucose <70 mg/dL) was experienced by six subjects during control, five subjects during insulin reduction, and none with glucose tablets or MDG; five subjects experienced hyperglycemia (plasma glucose ≥250 mg/dL) with glucose tablets and one with MDG.

MDG may be more effective than insulin reduction for preventing exercise-induced hypoglycemia and may result in less postintervention hyperglycemia than ingestion of carbohydrate.