Insulin-based Strategies to Prevent Hypoglycemia During Exercise

Study Overview
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Brief Summary
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It has been reported that insulin basal rate reduction initiated at exercise onset can reduce the hypoglycemic risk during exercise. However, another potentially more efficient strategy to prevent exercise-induced hypoglycemia could be to reduce insulin basal rate a certain time prior to exercise. No study investigated what would be the best timing to initiate such temporary basal insulin reduction. Therefore, the objective of this study will be to compare the efficacy of three strategies to prevent exercise-induced hypoglycemia during a 45 min exercise at 60% VO2peak (moderate intensity): 1) reduce insulin basal rate at the time of exercise; 2) reduce insulin basal rate 20 minutes prior to exercise; 3) reduce insulin basal rate 40 minutes prior to exercise. Investigators hypothesize that the time spent in hypoglycemia will be less when the insulin basal rate is reduced 40 minutes prior to exercise compared to a reduction at the time of exercise. Secondary hypotheses are: 1) Time spent in hypoglycemia will be less when the insulin basal rate is reduced 20 minutes prior to exercise compared to a reduction at the time of exercise; 2) Time spent in hypoglycemia will be less when the insulin basal rate is reduced 40 minutes prior to exercise compared to a reduction 20 minutes prior to exercise.

Official Title
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Reduction of Basal Insulin to Prevent Hypoglycemia During Exercise in Adults With Type 1 Diabetes Using Insulin Pump Therapy

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Other: Exercise 1
* Other: Exercise 2
* Other: Exercise 3


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females ≥ 18 years of old. Clinical diagnosis of type 1 diabetes for at least one year. The subject will have been on insulin pump therapy for at least 3 months. Last (less than 2 months) HbA1c ≤ 12%. Exclusion Criteria: Clinically significant microvascular complications: nephropathy (estimated glomerular filtration rate below 40 ml/min), neuropathy (especially diagnosed gastroparesis) or severe proliferative retinopathy as judged by the investigator. Recent (< 3 months) acute macrovascular event e.g. acute coronary syndrome or cardiac surgery. Abnormal blood panel and/or anemia. Ongoing pregnancy. Severe hypoglycemic episode within two weeks of screening. Other serious medical illness likely to interfere with study participation or with the ability to complete the exercise periods by the judgment of the investigator (e.g. orthopedic limitation). Failure to comply with team's recommendations (e.g. not willing to change pump parameters, etc.).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Reduction of insulin basal rate at the time of exercise<br> | Other: Exercise 1<br>* Participants will be admitted at IRCM at 14:00. At 15:30, participant's insulin basal rate will be reduced by 80% and participants will perform a 45-minute exercise on the ergocycle at 60% of VO2 peak (moderate intensity). At 16:15, the participant's usual insulin basal rate will be set in the insulin pump and a standardized snack (30g CHO) will be served. At 16:45, the participant will be discharged and will be asked to eat a standardized dinner at home (60g CHO for females and 80g CHO for males).<br>|
| Active Comparator: Reduction of insulin basal rate 20 minutes prior to exercise<br> | Other: Exercise 2<br>* Participants will be admitted at IRCM at 14:00. At 15:10, participant's insulin basal rate will be reduced by 80%. At 15:30, participants will perform a 45-minute exercise on the ergocycle at 60% of VO2 peak (moderate intensity). At 16:15, the participant's usual insulin basal rate will be set in the insulin pump and a standardized snack (30g CHO) will be served. At 16:45, the participant will be discharged and will be asked to eat a standardized dinner at home (60g CHO for females and 80g CHO for males).<br>|
| Active Comparator: Reduction of insulin basal rate 40 minutes prior to exercise<br> | Other: Exercise 3<br>* Participants will be admitted at IRCM at 14:00. At 14:50, participant's insulin basal rate will be reduced by 80%. At 15:30, participants will perform a 45-minute exercise on the ergocycle at 60% of VO2 peak (moderate intensity). At 16:15, the participant's usual insulin basal rate will be set in the insulin pump and a standardized snack (30g CHO) will be served. At 16:45, the participant will be discharged and will be asked to eat a standardized dinner at home (60g CHO for females and 80g CHO for males).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of time of capillary blood glucose levels spent below 4 mmol/L | This time frame corresponds to the exercise period. The exercise period will be from 15:30 to 16:15 | This outcome will be measured over 45 minutes. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Decrease in glucose levels | Difference between glucose levels at the beginning of the exercise and the lowest glucose level from the start of the exercise until the end of exercise. This time frame corresponds to the exercise period. The exercise period will be from 15:30 to 16:15 | This outcome will be measured over 45 minutes. | 
| Decremental area under the curve of sensor glucose levels | This time frame corresponds to the exercise period. The exercise period will be from 15:30 to 16:15 | This outcome will be measured over 45 minutes. | 
| Area under the curve of sensor glucose levels < 4 mmol/L | This time frame corresponds to the exercise period. The exercise period will be from 15:30 to 16:15 | This outcome will be measured over 45 minutes. | 
| Number of patients with an exercise-induced hypoglycemia < 3.9 mmol/L | This time frame corresponds to the exercise period. The exercise period will be from 15:30 to 16:15 | This outcome will be measured over 45 minutes. | 
| Number of patients with an exercise-induced hypoglycemia < 3.5 mmol/L | This time frame corresponds to the exercise period. The exercise period will be from 15:30 to 16:15 | This outcome will be measured over 45 minutes. | 
| Number of patients requiring an oral treatment for hypoglycemia | This time frame corresponds to the exercise period. The exercise period will be from 15:30 to 16:15 | This outcome will be measured over 45 minutes. | 
| Total number of hypoglycemia episode requiring treatment | This time frame corresponds to the exercise period. The exercise period will be from 15:30 to 16:15 | This outcome will be measured over 45 minutes. | 
| Percentage of time spent between 4 and 10 mmol/L | This time frame corresponds to the exercise period. The exercise period will be from 15:30 to 16:15 | This outcome will be measured over 45 minutes. | 
| Mean time (minutes) to the first hypoglycemic event | This time frame corresponds to the exercise period. The exercise period will be from 15:30 to 16:15 | This outcome will be measured over 45 minutes. | 
| Percentage of time spent < 4.0 mmol/L | This time frame corresponds to the post-exercise period, from the end of the exercise until 7:00 the next morning. | This outcome will be measured over 14.75 hours. | 
| Percentage of time of sensor glucose levels spent below 4 mmol/L | This time frame corresponds to the exercise period. The exercise period will be from 15:30 to 16:15 | This outcome will be measure over 45 minutes | 
| Absolute difference between capillary blood glucose levels and sensor glucose levels | This time frame corresponds to the exercise period. The exercise period will be from 15:30 to 16:15 | This outcome will be measure over 45 minutes | 
| Relative difference between capillary blood glucose levels and sensor glucose levels | This time frame corresponds to the exercise period. The exercise period will be from 15:30 to 16:15 | This outcome will be measure over 45 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 1 diabetes, Exercise, Hypoglycemia, Insulin pump