Afternoon vs Morning Exercise for Prediabetes

(TIMED Trial)

Overseen By Frédérique Frisch

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Université de Sherbrooke

Must not be taking: Lipid drugs, Carbohydrate drugs

Disqualifiers: Cardiovascular disease, Liver disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

48 Participants Needed

Trial Summary

What is the purpose of this trial?

Exercise is well-known to improve skeletal muscle energy metabolism and is an established intervention to improve muscle insulin sensitivity and to counter the development of type 2 diabetes (T2D). However, given the 24h rhythmicity in substrate metabolism previously observed in healthy, lean men and the lack of such rhythmicity in men with insulin-resistance, the investigator hypothesize that appropriate timing of exercise training can maximize the metabolic health effects of exercise. Indeed, a preliminary study in humans revealed that afternoon high-intensity interval training (HIIT) exercise was more effective than morning exercise in improving 24h blood glucose levels in men with T2D. Another recent study in mice showed that the time of day is a critical factor in augmenting the beneficial effects of exercise on the skeletal muscle metabolome as well as on whole-body energy homeostasis. However, human studies that specifically target the impact of timing of exercise training on glucose homeostasis and metabolic health are scarce and the potential underlying mechanisms largely unknown. The overarching goals of this project is to improve 24-hour rhythmicity of metabolism in men and women with prediabtes by appropriate timing of exercise and to assess its effect on metabolic health and immune response. Acute and prolonged exercise interventions timed in the morning vs late afternoon will be carried out in individuals with prediabetes to determine whether acute exercise in the afternoon and prolonged exercise training in the afternoon can improve peripheral insulin sensitivity, compared to exercise in the morning, and positively affect adipose tissue dietary fatty acid storage and partitioning of dietary fatty acids in skeletal muscles.

Will I have to stop taking my current medications?

Yes, you will need to stop taking certain medications. Statins must be stopped 3 weeks before the study, and metformin or anti-hypertensive drugs must be stopped 7 days before the study.

What data supports the effectiveness of the treatment High-intensity interval training (HIIT) for prediabetes?

Research shows that HIIT is effective in improving blood sugar control and reducing the risk of developing type 2 diabetes in people with prediabetes. It is a time-efficient exercise method that significantly lowers A1C (a measure of average blood sugar levels) and fasting blood glucose, with high-volume HIIT being more effective than low-volume HIIT. ^{1 2 3 4 5}

Is high-intensity interval training (HIIT) safe for humans?

Research on high-intensity interval training (HIIT) for people with prediabetes shows it is generally safe and effective for improving blood sugar control and reducing the risk of developing type 2 diabetes. HIIT is a time-efficient exercise option that can improve heart and metabolic health, making it a safe choice for those with limited time to exercise. ^{2 3 4 6 7}

How does high-intensity interval training (HIIT) differ from other treatments for prediabetes?

High-intensity interval training (HIIT) is unique because it offers a time-efficient way to improve blood sugar control and reduce the risk of developing type 2 diabetes, especially when performed in the afternoon. Unlike traditional moderate-intensity exercise, HIIT requires less time commitment while providing superior benefits for insulin sensitivity and metabolic health. ^{3 4 6 8 9}

Research Team

Denis P. Blondin, PhD

Principal Investigator

Université de Sherbrooke

Eligibility Criteria

This trial is for men and women with prediabetes, defined by specific blood sugar levels or insulin resistance. Participants must have a BMI over 25, be able to follow the study protocol, and provide informed consent. Exclusions include recent scans, smoking, heavy drinking, certain medical conditions like uncontrolled thyroid disorders or heart disease, and use of medications affecting metabolism.

Inclusion Criteria

To be willing and able to adhere to the specifications of the protocol

To have signed an informed consent document indicating that they understood the purpose of and procedures required for the study and were willing to participate in the study.

I have pre-diabetes or insulin resistance based on my blood sugar tests.

Exclusion Criteria

My cholesterol or triglycerides levels have been high.

You have a pacemaker.

I have heart disease confirmed by my doctor and tests.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Metabolic Study

Participants complete Visit A (baseline) followed by a glycogen lowering exercise bout

1-2 weeks

2 visits (in-person)

Acute Exercise and Metabolic Study

Participants undergo an acute exercise bout and return for Visit B 18-24 hours later

1 week

2 visits (in-person)

12-week Exercise Training

Participants engage in a 12-week supervised high-intensity interval training program

12 weeks

Regular visits every other day

Final Metabolic Study

Participants return for Visit C at least 48 hours after the last exercise bout

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the intervention

4 weeks

Treatment Details

Interventions

• High-intensity interval training

Trial Overview The trial tests whether exercising at different times (morning vs late afternoon) affects blood sugar control in people with prediabetes. It aims to see if timing exercise can improve how the body uses insulin and manages dietary fats in muscles and fat tissue.

Participant Groups

Group I: Afternoon exercise Experimental Treatment 1 Intervention

Participant to perform high-intensity interval training in the morning (\~4 pm)

Group II: Morning exercise Active Control 1 Intervention

Participant to perform high-intensity interval training in the morning (\~9 am)

Who Is Running the Clinical Trial?

Université de Sherbrooke

Lead Sponsor

Trials

317

Recruited

79,300+

Laval University

Collaborator

Trials

439

Recruited

178,000+

Wageningen University

Collaborator

Trials

177

Recruited

44,600+

McMaster University

Collaborator

Trials

936

Recruited

2,630,000+

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Collaborator

Trials

722

Recruited

2,726,000+

Maastricht University Medical Center

Collaborator

Trials

992

Recruited

3,304,000+

University of Calgary

Collaborator

Trials

827

Recruited

902,000+

University of Waterloo

Collaborator

Trials

132

Recruited

221,000+

Leiden University Medical Center

Collaborator

Trials

580

Recruited

623,000+

Findings from Research

A 12-week elliptical high-intensity interval training (HIIT) program significantly improved metabolic risk factors in 16 participants with pre- and type 2 diabetes, including reductions in fasting blood glucose and waist circumference.

Participants also experienced enhancements in body composition, such as increased lean body mass and improved cardiovascular fitness (VO2max), indicating that HIIT can be an effective intervention for managing diabetes-related health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Elliptical High Intensity Interval Training on Metabolic Risk Factor in Pre- and Type 2 Diabetes Patients: A Pilot Study. Fex, A., Leduc-Gaudet, JP., Filion, ME., et al.[2022]

A 6-week high-intensity interval training (HIT) program, requiring less than 15 minutes per session, significantly improved key health markers in 189 sedentary adults with pre-existing risk factors for type 2 diabetes, including a 10% increase in fitness levels and a 16% reduction in insulin resistance.

The HIT protocol also effectively lowered mean arterial blood pressure by 3%, demonstrating that this time-efficient exercise regimen can be as effective as longer, traditional exercise programs in managing cardio-metabolic risk factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Practical and Time-Efficient High-Intensity Interval Training Program Modifies Cardio-Metabolic Risk Factors in Adults with Risk Factors for Type II Diabetes. Phillips, BE., Kelly, BM., Lilja, M., et al.[2019]

High-intensity (HI) exercise training is a time-efficient alternative to traditional moderate-intensity (MI) exercise for prediabetic adults, allowing them to meet physical activity guidelines with less overall time commitment.

HI exercise training has been shown to improve skeletal muscle metabolic control and cardiovascular function comparably or even superiorly to low-intensity (LI) and MI exercise, making it an effective option for reducing cardiometabolic risk in prediabetic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-intensity exercise training for the prevention of type 2 diabetes mellitus. Rynders, CA., Weltman, A.[2014]

High-intensity interval training (HIIT) is effective in improving glycemic control in overweight adults with prediabetes, as shown in a study involving 60 participants over 12 weeks.

Among the HIIT methods tested, high-volume HIIT (HV-HIIT) was more effective than low-volume HIIT (LV-HIIT) in significantly reducing A1C and fasting blood glucose levels, suggesting it may better prevent progression to type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Different Dosages of Interval Training on Glycemic Control in People With Prediabetes: A Randomized Controlled Trial. RezkAllah, SS., Takla, MK.[2020]

High-intensity interval training (HIIT) significantly improves functional capacity, as measured by VO2max, by 3.02 mL/kg/min compared to moderate-intensity continuous training (MICT) in individuals with prediabetes and type 2 diabetes (T2D).

Both HIIT and MICT show similar effects on cardiometabolic markers such as HbA1c and cholesterol levels, indicating that while HIIT may enhance physical fitness, it does not provide additional benefits for metabolic health compared to MICT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-intensity interval training versus continuous training on physiological and metabolic variables in prediabetes and type 2 diabetes: A meta-analysis. De Nardi, AT., Tolves, T., Lenzi, TL., et al.[2018]

A 12-week study involving 32 prediabetic male patients showed that high-intensity interval training (HIIT) significantly reduced blood glucose levels compared to continuous endurance training at anaerobic threshold (CETAT).

Both HIIT and continuous endurance training at maximal fat oxidation (CETFAT) improved insulin resistance indices similarly, indicating that exercise intensity and type can effectively influence hormonal changes in prediabetic individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Intensity Interval vs. Continuous Endurance Training: Preventive Effects on Hormonal Changes and Physiological Adaptations in Prediabetes Patients. Safarimosavi, S., Mohebbi, H., Rohani, H.[2022]

Individuals with prediabetes showed better adherence to high-intensity interval training (HIIT) compared to traditional moderate-intensity continuous training (MICT), with adherence rates of 89% for HIIT versus 71% for MICT after one month.

Participants in the HIIT group engaged in significantly more vigorous physical activity per week (24 minutes) compared to those in the MICT group (11 minutes), while both groups experienced similar improvements in cardiorespiratory fitness and blood pressure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-intensity interval training as an efficacious alternative to moderate-intensity continuous training for adults with prediabetes. Jung, ME., Bourne, JE., Beauchamp, MR., et al.[2022]

In a 12-week exercise program involving 32 adult males at risk for type 2 diabetes, afternoon exercise training resulted in significantly better improvements in insulin sensitivity and metabolic health compared to morning training.

Participants who exercised in the afternoon showed greater reductions in fasting plasma glucose levels, fat mass, and improved exercise performance, suggesting that the timing of exercise can influence its effectiveness for metabolic health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise training elicits superior metabolic effects when performed in the afternoon compared to morning in metabolically compromised humans. Mancilla, R., Brouwers, B., Schrauwen-Hinderling, VB., et al.[2021]

A 16-week supervised high-intensity aerobic exercise program significantly improved health markers in individuals with metabolic syndrome, including body composition, blood pressure, and cardiorespiratory fitness, with no differences between morning and afternoon exercise groups.

However, morning exercise (AMEX) was more effective than afternoon exercise (PMEX) in reducing systolic blood pressure and insulin resistance, suggesting that the timing of exercise can influence cardiometabolic health benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of morning versus afternoon aerobic exercise training on reducing metabolic syndrome components: A randomized controlled trial. Morales-Palomo, F., Moreno-Cabañas, A., Alvarez-Jimenez, L., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Effect of Elliptical High Intensity Interval Training on Metabolic Risk Factor in Pre- and Type 2 Diabetes Patients: A Pilot Study. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

A Practical and Time-Efficient High-Intensity Interval Training Program Modifies Cardio-Metabolic Risk Factors in Adults with Risk Factors for Type II Diabetes. [2019]

3. England pubmed.ncbi.nlm.nih.gov

High-intensity exercise training for the prevention of type 2 diabetes mellitus. [2014]

4. United States pubmed.ncbi.nlm.nih.gov

Effects of Different Dosages of Interval Training on Glycemic Control in People With Prediabetes: A Randomized Controlled Trial. [2020]

5. Ireland pubmed.ncbi.nlm.nih.gov

High-intensity interval training versus continuous training on physiological and metabolic variables in prediabetes and type 2 diabetes: A meta-analysis. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

High-Intensity Interval vs. Continuous Endurance Training: Preventive Effects on Hormonal Changes and Physiological Adaptations in Prediabetes Patients. [2022]

7. England pubmed.ncbi.nlm.nih.gov

High-intensity interval training as an efficacious alternative to moderate-intensity continuous training for adults with prediabetes. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Exercise training elicits superior metabolic effects when performed in the afternoon compared to morning in metabolically compromised humans. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Efficacy of morning versus afternoon aerobic exercise training on reducing metabolic syndrome components: A randomized controlled trial. [2023]