Clinical trial NCT05115682: Circadian Rhythm and Metabolic Effects of Exercise
Official title: Time of Day Specific Glycaemic and Metabolic Response to High-Intensity Interval Training
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diabetes Mellitus, Type 2
Circadian Rhythm
Glycemic Control
Keywords: Type 2 Diabetes
High-intensity Intermittent Exercise
Circadian Rhythm
Glycemic Control
Energy Metabolism
Lead sponsor: Karolinska Institutet
Sponsor class: OTHER
Collaborators: name: Karolinska University Hospital
First posted: 2021-11-10
Enrollment: 48
Sex: ALL
Minimum age (years): 45
Maximum age (years): 68
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: The study will include a group of individuals with type 2 diabetes and a group of individuals with normal glucose tolerance. Each group of participants will complete either a morning (09:00) or an afternoon (16:00) exercise bout. After a one-week washout period, the participants will complete an additional exercise bout at the opposing time.
Primary purpose: BASIC_SCIENCE

Brief summary: Physical exercise is efficacious in controlling blood glucose levels in individuals with Type 2 diabetes. An individual's exercise capacity and ability to utilize glucose as an energy source oscillates throughout the day. Hence, the beneficial effects of exercise on blood glucose levels may depend on the time of day when the exercise bout is performed. However, the time of day in which the most beneficial adaptations to exercise can be achieved remains unknown. This project aims to answer the following questions: Does time of day impact the beneficial effects of exercise on blood glucose? If so, when can the most beneficial effects of exercise be achieved? Which metabolic mechanisms links time of day, exercise and blood glucose control? To address these questions, individuals with or without Type 2 diabetes will perform an exercise session at two different times (09:00 and 16:00), and continuous glucose monitoring will be used to assess the effects of exercise on blood glucose. We will determine the specific metabolic processes which promote the most beneficial blood glucose response. To achieve this, we will measure which metabolic substrates (carbohydrates, lipids and proteins) are used and which metabolites produced in blood, skeletal muscle and adipose tissue in response to exercise at different times of the day.

Detailed description: Exercise has well-established metabolic benefits and is a preferred intervention for Type 2 diabetes prevention and management. Metabolic determinants of exercise such as skeletal muscle and whole-body substrate oxidation capacity, glucose tolerance and insulin sensitivity and adipose tissue fatty acid release all show circadian oscillations. These rhythms may promote substantially different responses depending on the time of day when exercise is performed.

This is an exploratory study aiming to determine whether exercise at specific times of day can amplify the beneficial effects on glycemia and metabolism in two groups of individuals: those without diabetes or those with Type 2 diabetes (n=40 per group). The primary objective is to determine the glycemic response to an exercise bout at two distinct times of day, measured by continuous glucose monitoring, in men and women with or without Type 2 diabetes. The secondary aim is to identify specific metabolites which facilitate the strongest glycemic response to exercise by examining the whole-body and peripheral tissue metabolomic response to an exercise bout.

The primary goal of the study is to examine the glycemic and metabolic response to exercise within-group for participants with or without Type 2 diabetes. Further comparisons will be made between groups with with or without Type 2 diabetes, across sexes, and by individual chronotype (determined by a standardized questionnaire) to examine the variation in the exercise response across these parameters.

Eligibility criteria: Inclusion Criteria:

* Body Mass Index (BMI): 23 - 33 kg/m2
* Participants diagnosed with Type 2 Diabetes (insulin independent) or participants without Type 2 Diabetes (based on normal HbA1c and fasting glucose levels).
* Ability to provide informed consent
* Ability to complete the exercise regiment

Exclusion Criteria:

* Medications: Insulin
* Current nicotine user (cigarettes, snus, nicotine gum) or past nicotine users less than 6 months before inclusion in the study
* Pre-existing cardiovascular condition (Angina pectoris, Cardiac arrhythmia, Cardiac infarction, Coronary stent / angiography, Cerebrovascular insult, Hypertension \[\> 160 mmHg systolic, or \> 95 mmHg diastolic\])
* Pre-existing blood-borne disease (HIV, Hepatitis C, MRSA)
* Pre-existing systemic or localized rheumatic illness
* Malignant Disease
* Pre-existing psychiatric disorder
* Another pre-existing systemic disease

Primary outcomes:
measure: Exercise-induced Changes in 24 Hour Interstitial Glucose Concentration
timeFrame: 3 days (1 day before to 1 day after exercise)
Secondary outcomes:
measure: Acute Exercise-induced Changes in Interstitial Glucose Concentration
timeFrame: 2 hours (0 minutes before to 120 minutes after exercise)
measure: Interstitial Glucose Concentration Response to a Meal
timeFrame: 2 days (1 day before and day of exercise)
measure: Interstitial Glucose Concentration Variability
timeFrame: 3 days (1 day before to 1 day after exercise)
measure: Time Spent in Interstitial Glucose Concentration Range
timeFrame: 3 days (1 day before to 1 day after exercise)
measure: Nocturnal Interestitial Glucose Concentration
timeFrame: 2 days (day of, and 1 day after exercise)
measure: Metabolic Response to Exercise
timeFrame: 1 hour (5 minutes before, 5 minutes after and 60 minutes after exercise)
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: Karolinska Institutet
Study officials:
affiliation: Karolinska Institutet
name: Harriet Wallberg-Henriksson, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: