Diabetes Mellitus, Type 2HITMetNCT05115682
Circadian Rhythm and Metabolic Effects of Exercise
A study testing High-intensity Intermittent Exercise in people with Diabetes Mellitus, Type 2 and Circadian Rhythm, run by Karolinska Institutet at 1 site in Sweden.
Trial 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. Read more about this study
- Who is it for?
- Ages 45 to 68 yearsHealthy volunteers can take part
- Conditions the study is for
- Diabetes Mellitus, Type 2, Circadian Rhythm, Glycemic Control
- What is being tested?
- High-intensity Intermittent Exercise
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteSweden
- Study dates
- 10 Nov 2021to 25 Jun 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 to 68 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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 locations and contacts
1 site in 1 country.
About this study
Official title: Time of Day Specific Glycaemic and Metabolic Response to High-Intensity Interval Training
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.
Read the 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.
- Being tested
- High-intensity Intermittent Exercise
- Keywords
- Type 2 Diabetes, High-intensity Intermittent Exercise, Circadian Rhythm, Glycemic Control, Energy Metabolism
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High-intensity Intermittent ExerciseBehavioural
The participants will perform a low-volume, High-intensity Intermittent Exercise bout on a cycle ergometer. Peak exercise capacity of the study participants will be determined on a separate occasion using a ramp-up maximal oxygen consumption test (VO2peak). A single exercise bout will consist of a 7-minute warm-up on a cycle ergometer, followed by 6 1-minute intervals of cycling at individual maximal capacity and 75rpm (rotations per minute). These intervals will be interspersed with 1-min breaks of cycling at low resistance and 75rpm, and the session will conclude with a 3-minute cool-down interval (20 minutes in total).
| Study group | Role | What they receive |
|---|---|---|
| Morning First | Experimental | 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. Receives: Behavioral: High-intensity Intermittent Exercise |
| Afternoon First | Experimental | 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. Receives: Behavioral: High-intensity Intermittent Exercise |
What is being measured
The primary outcome is the main question the study is designed to answer.
Exercise-induced Changes in 24 Hour Interstitial Glucose Concentration
Glucose excursions will be charted using continuous interstitial glucose monitors. The day immediately before exercise will be used as baseline, the day of exercise to assess the acute response, and the day after exercise to assess lasting effects on glycemia. Exercise effects on glucose concentration will be primarily assessed by comparing 24-hour curves between conditions.
Measured: 3 days (1 day before to 1 day after exercise)
Secondary outcomes (6)
Acute Exercise-induced Changes in Interstitial Glucose Concentration
Glucose will be charted using continuous glucose monitors. Acute response to exercise, during the exercise bout and during an additional 120 minutes will be compared between conditions.
Measured: 2 hours (0 minutes before to 120 minutes after exercise)
Interstitial Glucose Concentration Response to a Meal
Glucose will be charted using continuous glucose monitors. Three standardized meals per day will be provided on each occasion for the day before, day of and day after exercise. The 120 minute glucose response to the standardized meal succeeding an exercise bout will be compared to the same meal on a baseline (no exercise) day and between the two exercise times.
Measured: 2 days (1 day before and day of exercise)
Interstitial Glucose Concentration Variability
Glucose will be charted using continuous glucose monitors. The day immediately before exercise will be used as baseline, the day of exercise to assess the acute response, and the day after exercise to assess lasting effects on glucose concentration variability.
Measured: 3 days (1 day before to 1 day after exercise)
Time Spent in Interstitial Glucose Concentration Range
Glucose will be charted using continuous glucose monitors. The day immediately before exercise will be used as baseline, the day of exercise to assess the acute response, and the day after exercise to assess lasting effects on glycemic variability. Daily time spent in low (<3.9mmol/L), high (>10mmol/L) and within target glycemic range (3.9-10mmol/L) will be calculated on each occasion.
Measured: 3 days (1 day before to 1 day after exercise)
Nocturnal Interestitial Glucose Concentration
Glucose will be charted using continuous glucose monitors. The day immediately before exercise will be used as baseline, the day of exercise to assess the acute response, and the day after exercise to assess lasting effects on glycemic variability. Nocturnal glycemia (00:00-06:00) for each day will be compared on each exercise occasion.
Measured: 2 days (day of, and 1 day after exercise)
Metabolic Response to Exercise
Changes in blood, skeletal muscle and subcutaneous adipose tissue metabolite levels will be assessed by broad-spectrum, untargeted metabolomics. Samples will be collected immediately before (-5 minutes) and after (+5 minutes) each exercise bout. An additional blood sample will be collected one hour after exercise completion (+60 minutes).
Measured: 1 hour (5 minutes before, 5 minutes after and 60 minutes after exercise)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2021
- Study start10 Nov 2021
- Primary completion25 Jun 2024
- Study completion25 Jun 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- More trials run by Karolinska InstitutetThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- 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.
- Masking
- None (open label)
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Karolinska Institutet
- Sponsor type
- University, hospital or other
- Collaborators
- Karolinska University Hospital
- Responsible party
- Principal investigator, Harriet Wallberg, Karolinska Institutet
- Investigators
- Harriet Wallberg-Henriksson, MD PhD, Principal investigator, Karolinska Institutet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05115682
- Sponsor's protocol ID
- HIT Metabolome
- Acronym
- HITMet
- Status last verified
- Feb 2025
- First submitted
- 19 Oct 2021
- Last updated
- 21 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data underlying results reported in a publication will be shared after deidentification.
Publications
Keller MJ, Brady AJ, Smith JAB, Savikj M, MacGregor K, Jollet M, Oberg SB, Nylen C, Bjornholm M, Rickenlund A, Carlsson M, Caidahl K, Krook A, Pillon NJ, Zierath JR, Wallberg-Henriksson H. Inflammatory markers and blood glucose are higher after morning vs afternoon exercise in type 2 diabetes. Diabetologia. 2025 Sep;68(9):2023-2035. doi: 10.1007/s00125-025-06477-5. Epub 2025 Jun 28.
PubMed 40580209
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Time of Day Specific Glycaemic and Metabolic Response to High-Intensity Interval Training
- ClinicalTrials.gov ID
- NCT05115682
- Acronym / sponsor ID
- HITMet / HIT Metabolome
- Keywords
- Type 2 Diabetes, High-intensity Intermittent Exercise, Circadian Rhythm, Glycemic Control, Energy Metabolism
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Karolinska InstitutetUniversity, hospital or other
- Collaborators
- Karolinska University Hospital
- Study start
- 10 Nov 2021 (actual)
- Primary completion
- 25 Jun 2024 (actual)
- Study completion
- 25 Jun 2024 (actual)
- First posted
- 10 Nov 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Morning First | Experimental | Behavioral: High-intensity Intermittent ExerciseParticipants 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. |
| Afternoon First | Experimental | Behavioral: High-intensity Intermittent ExerciseParticipants 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. |
Who may qualify
- Ages
- 45 to 68 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| High-intensity Intermittent ExerciseThe participants will perform a low-volume, High-intensity Intermittent Exercise bout on a cycle ergometer. Peak exercise capacity of the study participants will be determined on a separate occasion using a ramp-up maximal oxygen consumption test (VO2peak). A single exercise bout will consist of a 7-minute warm-up on a cycle ergometer, followed by 6 1-minute intervals of cycling at individual maximal capacity and 75rpm (rotations per minute). These intervals will be interspersed with 1-min breaks of cycling at low resistance and 75rpm, and the session will conclude with a 3-minute cool-down interval (20 minutes in total). | Behavioural | Afternoon First, Morning First |
Primary outcome
Exercise-induced Changes in 24 Hour Interstitial Glucose Concentration
Time frame: 3 days (1 day before to 1 day after exercise)
Glucose excursions will be charted using continuous interstitial glucose monitors. The day immediately before exercise will be used as baseline, the day of exercise to assess the acute response, and the day after exercise to assess lasting effects on glycemia. Exercise effects on glucose concentration will be primarily assessed by comparing 24-hour curves between conditions.
6 secondary outcomes
Acute Exercise-induced Changes in Interstitial Glucose Concentration
Time frame: 2 hours (0 minutes before to 120 minutes after exercise)
Interstitial Glucose Concentration Response to a Meal
Time frame: 2 days (1 day before and day of exercise)
Interstitial Glucose Concentration Variability
Time frame: 3 days (1 day before to 1 day after exercise)
Time Spent in Interstitial Glucose Concentration Range
Time frame: 3 days (1 day before to 1 day after exercise)
Nocturnal Interestitial Glucose Concentration
Time frame: 2 days (day of, and 1 day after exercise)
Metabolic Response to Exercise
Time frame: 1 hour (5 minutes before, 5 minutes after and 60 minutes after exercise)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2025.
- Derived from this study: PubMed 40580209Keller MJ, Brady AJ, Smith JAB, Savikj M, MacGregor K, Jollet M, Oberg SB, Nylen C, Bjornholm M, Rickenlund A, Carlsson M, Caidahl K, Krook A, Pillon NJ, Zierath JR, Wallberg-Henriksson H. Inflammatory markers and blood glucose are higher after morning vs afternoon exercise in type 2 diabetes. Diabetologia. 2025 Sep;68(9):2023-2035. doi: 10.1007/s00125-025-06477-5. Epub 2025 Jun 28.
- Individual participant dataSharing planned: Yes. Individual participant data underlying results reported in a publication will be shared after deidentification.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Harriet Wallberg-Henriksson, MD PhD principal investigator
Karolinska Institutet
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing High-intensity Intermittent Exercise in people with Diabetes Mellitus, Type 2 and Circadian Rhythm, run by Karolinska Institutet at 1 site in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Exercise-induced Changes in 24 Hour Interstitial Glucose Concentration (time frame: 3 days (1 day before to 1 day after exercise)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05115682, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Feb 2025.