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

• Published in: Diabetes care Vol. 41; no. 9; pp. 1909 - 1916
• Main Authors: Rickels, Michael R, DuBose, Stephanie N, Toschi, Elena, Beck, Roy W, Verdejo, Alandra S, Wolpert, Howard, Cummins, Martin J, Newswanger, Brett, Riddell, Michael C
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01-09-2018
• Subjects: Adult; Adults; Autoimmune diseases; Blood glucose; Blood Glucose - metabolism; Blood levels; Carbohydrates; Cross-Over Studies; Diabetes; Diabetes mellitus; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - complications; Diabetes Mellitus, Type 1 - drug therapy; Dose-Response Relationship, Drug; Emerging Therapies: Drugs and Regimens; Exercise; Exercise - physiology; Fasting - blood; Female; Glucagon; Glucagon - administration & dosage; Glucagon - adverse effects; Glucose; Glucose - administration & dosage; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemia - etiology; Hypoglycemia - prevention & control; Ingestion; Insulin; Insulin - administration & dosage; Insulin - adverse effects; Insulin Infusion Systems - adverse effects; Male; Oxygen consumption; Reduction; Research design; Tablets
• ISSN: 0149-5992; 1935-5548
• DOI: 10.2337/dc18-0051

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
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 (
< 0.001). Insulin levels were not different among sessions, whereas glucagon increased with MDG administration (
< 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.