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

Abstract

Objective: 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.

Research design and methods: 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% VO2max for 45 min under conditions of no intervention (control), 50% basal insulin reduction, 40-g oral glucose tablets, or 150-μg subcutaneous glucagon (MDG).

Results: 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.

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

Trial registration: ClinicalTrials.gov NCT02660242.

© 2018 by the American Diabetes Association.

Figures

Figure 1

Plasma glucose (A and B), glucagon (C and D), and insulin (E and F) during exercise and early recovery (A, C, and E) and during the subsequent ingestion of a standardized meal (B, D, and F). Treatment with glucose tablets (▽), MDG (-■-), insulin reduction (-○-), or no intervention (control; △) occurred 5 min prior to the start of exercise, and an insulin bolus was administered using each participant’s insulin-to-carbohydrate ratio 5 min prior to meal ingestion. Data are the mean ± SD.

Figure 2

Occurrence of hypoglycemia and hyperglycemia under conditions of no intervention (control), basal insulin reduction, oral glucose tablets, or MDG administered 5 min prior to the start of exercise and assessed by plasma glucose during the 45 min of exercise and 30 min of early recovery (A) as well as for the subsequent 90 min after bolus insulin administration and ingestion of a standardized meal (B). Black bar represents control; vertical stripes represent insulin reduction; white bar represents glucose tabs; horizontal stripes represent MDG.

Figure 3

Interstitial glucose from CGM during late recovery, shown relative to the time elapsed since the start of the late recovery period (90 min after the standardized meal). Data are the mean ± SD.