The Impact of Subcutaneous Glucagon Before, During and After Exercise a Study in Patients With Type 1 Diabetes Mellitus

Design:

A randomized placebo-controlled single-blinded study will be conducted. The subjects do not know if they get glucagon or placebo but the investigator know if the subject get glucagon or placebo. Study participants have to complete three study days and serve as their own controls. After participants have given an informed consent, they will go through three steps:

• Screening day
• Run-in period
• Three study days in a random order:

• Exercise and glucagon injected after cycling/or during cycling in case of hypoglycemia
• Resting and glucagon after resting
• Exercise and glucagon subcutaneous before cycling

47-49 hours before the study visits one CGM device is placed on the abdominal wall on the participant at least 7 cm from the site of the insulin pump infusion set. One CGM is placed on the non-dominant upper arm between 10 cm from elbow and 10 cm from shoulder on the posterior/lateral side on the arm. The CGMs will be in place for seven days. The CGM readings on the CGM placed at the abdominal wall are not blinded for the participant. The CGM readings on the CGM placed on the arm is blinded for the participant. In the period from the study visits to 4 days after the study visits the participant will do self-monitoring of blood glucose 8 times a day on standardized times.

Inclusion criteria

• Type 1 Diabetes ≥ 2 year
• BMI 20-30 kg/m2
• Insulin pump ≥ 1 year.
• HbA1c < 69 mmol/mol (8.5 %)
• Hypoglycemia awareness (reported by Gold et al.)
• Use of carbohydrate counting and the insulin pump bolus calculator for all meals
• Sedentary or mild physical activity: Less than 150 minutes of moderate-intensity aerobic physical activity throughout the week and less than 75 minutes of vigorous-intensity aerobic physical activity throughout the week .

Exclusion criteria

• Allergy or intolerance to lactose or GlucaGen® (Novo Nordisk, Bagsværd, DK)
• Impaired renal function (eGFR < 60 ml/min/1.73m2)
• Liver disease with ALAT > 2.5 times the upper limit of the reference interval
• Use of anti-diabetic medicine (other than insulin), per oral corticosteroids or other drugs affecting glucose metabolism during the study period or within 30 days prior to study start
• Known or suspected alcohol or drug abuse
• Other concomitant medical or psychological condition that according to the investigator's assessment makes the patient unsuitable for study participation
• Females who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods
• Inability to understand the patient information and to give informed consent
• Physical or mental incapacity to perform exercise
• Chronic use or unable to stop acetaminophen (paracetamol) use
• Allergy to the patch of CGM