Circadian Rhythm and Metabolic Effects of Exercise (HITMet)

Karolinska Institute

Status: Completed

Conditions: Glycemic Control; Circadian Rhythm; Diabetes Mellitus, Type 2

Treatments: Behavioral: High-intensity Intermittent Exercise

Study type: Interventional

Funder types: Other

Identifiers

NCT05115682

HIT Metabolome

Details and patient eligibility

About

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.

Full 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.

Enrollment: 48 patients

Sex: All

Ages: 45 to 68 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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48 participants in 2 patient groups

Morning First

Experimental group

Description:

Participants will complete a single bout of exercise at 09:00, and after at least a one-week washout perform another exercise bout at 16:00.

Treatment:

Behavioral: High-intensity Intermittent Exercise

Afternoon First

Experimental group

Description:

Participants will complete a single bout of exercise at 16:00, and after at least a one-week washout perform another exercise bout at 09:00.

Treatment:

Behavioral: High-intensity Intermittent Exercise