Morning vs Evening Exercise for Prediabetes

(TExIS Trial)

Overseen By Seth Creasy, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Colorado, Denver

Must not be taking: Oral steroids, Metformin, GLP1 agonists

Disqualifiers: Cardiovascular disease, Diabetes, CKD, others

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

Compensation: Varies

Number of Visits: 9

25 Participants Needed

Trial Summary

What is the purpose of this trial?

Purpose of the Study: This study is to learn more about how exercising at different times of the day (morning versus evening) affects metabolism of glucose in the body, sleep, activity outside of exercise, and other factors. Procedures: * 2 screening visits to make sure you are eligible to be in the study. This will include a fasting blood draw and heart tracing (EKG). * If you are eligible, you will complete both exercise conditions in a random order. All participants in the study will complete the following separated by 3-4 weeks: * Baseline condition of NO exercise * Morning exercise for 3 days in a row * Evening exercise for 3 days in a row * You will be provided with an example diet to follow for the days you are completing the baseline and exercise conditions (three days total for each condition). This diet will be a "traditional" diet with a controlled amount of carbohydrates, protein, and fat per day. The investigators will provide you with examples of meals to eat during this time. * You will be asked questions and complete questionnaires about your health history, sleeping and awakening habits, and sleepiness levels. * You will undergo one x-ray scan to measure your level of body fat. * You will be asked to wear an activity monitor and sleep monitor for 6 days in a row three times during this study. * You will be asked to wear a continuous glucose monitor (CGM) for 6 days in a row three times during this study. * You will be asked to measure your saliva melatonin levels three times in the study. This will be done once per hour for 5 hours (a total of 6 saliva samples). * You will be asked to complete a procedure called a "hyperinsulinemic-euglycemic clamp" where you will have an IV placed and insulin and glucose infused with frequent lab and finger stick blood sugars monitored closely. This will be done 3 times during the study.

Will I have to stop taking my current medications?

The trial requires that you do not use certain medications that affect insulin sensitivity, like oral steroids, metformin, or GLP1 receptor agonists. If you are taking these, you would need to stop before participating.

What data supports the effectiveness of the treatment Morning and Evening Exercise, Physical Activity, Exercise Therapy for prediabetes?

Research suggests that exercising in the afternoon may provide better benefits for people with metabolic issues, like prediabetes, compared to morning exercise. Afternoon exercise improved insulin sensitivity and reduced fasting blood sugar levels more effectively than morning exercise. ^{1 2 3 4 5}

Is exercise safe for people with prediabetes?

Exercise is generally safe for people with prediabetes, though there are some mild to severe risks like muscle injuries or low blood sugar. These risks are low, and with proper precautions, exercise can be a safe activity. ^{1 4 6 7 8}

How does the timing of exercise impact its effectiveness for prediabetes treatment?

This treatment is unique because it explores the timing of exercise, comparing morning and evening sessions, to optimize metabolic benefits for prediabetes. Research suggests that exercising in the afternoon may provide superior improvements in insulin sensitivity and glucose levels compared to morning exercise. ^{1 4 9 10 11}

Eligibility Criteria

This trial is for adults with prediabetes, which may include those who are overweight and lead a sedentary lifestyle. Participants should be willing to undergo various tests including blood draws, EKGs, x-rays, and wear monitors. They must follow a specific diet during the study and complete morning and evening exercise sessions.

Inclusion Criteria

Not currently pregnant or lactating, not pregnant within the past 6 months or planning to become pregnant in the next 6 months.

Weight stable (weight change < 5kg in past 3 months)

I am between 20 and 40 years old.

Exclusion Criteria

Current or recent (within 1 month) zero or very low carbohydrate diet (< 10% daily calories from carbohydrates)

Diastolic blood pressure > 100 mmHg, systolic blood pressure > 160 mmHg, or resting heart rate > 100 bpm

I have a history or symptoms of heart disease or heart failure.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

2 visits (in-person)

Baseline

Participants complete a baseline condition of no exercise with dietary control and monitoring

3 days

1 visit (in-person)

Morning Exercise

Participants perform morning exercise for 3 consecutive days with dietary control and monitoring

3 days

3 visits (in-person)

Evening Exercise

Participants perform evening exercise for 3 consecutive days with dietary control and monitoring

3 days

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after exercise conditions

4 weeks

Treatment Details

Interventions

• Morning and Evening Exercise

Trial Overview The study investigates how exercising in the morning versus the evening affects glucose metabolism in people with prediabetes. It involves no-exercise baseline measurements followed by three consecutive days of either AM or PM exercise, separated by 3-4 weeks.

Participant Groups

Group I: Crossover - PM first Experimental Treatment 2 Interventions

Crossover design with PM exercise first

Group II: Crossover - AM first Experimental Treatment 2 Interventions

Crossover design with AM exercise first

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

Findings from Research

Exercise, whether in the morning or evening, effectively delays the rise in nighttime glucose levels in individuals with obesity and impaired fasting glucose (OB+IFG), helping to manage glucose levels overnight.

However, while exercise helps control evening glucose spikes, it does not lower morning fasting glucose levels or improve the relationship between glucose and insulin concentrations in these individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temporal optimization of exercise to lower fasting glucose levels. Kanaley, JA., Porter, JW., Winn, NC., et al.[2023]

A study involving 30 individuals with type 2 diabetes showed that structured exercise aligned with their circadian rhythm significantly improved blood sugar levels, cholesterol profiles, functionality, and quality of life over 18 weeks.

Exercising at the right time for each person's chronotype led to the greatest improvements in health markers, indicating that timing of physical activity is crucial for managing type 2 diabetes effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of exercises according to the circadian rhythm in type 2 diabetes: Parallel-group, single-blind, crossover study. Menek, MY., Budak, M.[2022]

In a study of 113 elderly patients with prediabetes who completed a 2-year exercise intervention, factors such as baseline β-cell function, hemoglobin A1c levels, and body mass index were identified as significant predictors of whether participants would convert to diabetes or revert to normal glucose tolerance.

The type of exercise (aerobic vs. resistance) did not significantly impact the exercise response, suggesting that individual metabolic factors are more critical in determining the effectiveness of exercise in preventing diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

β-Cell function and body mass index are predictors of exercise response in elderly patients with prediabetes. He, Y., Feng, Y., Shi, J., 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]

This clinical trial will involve 210 participants with prediabetes to evaluate how different types and frequencies of exercise affect blood sugar control over 15 weeks, aiming to identify the most effective exercise regimen.

The study will not only measure changes in glycaemic control but also explore underlying mechanisms through gene expression analysis, potentially leading to improved exercise recommendations for diabetes prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Different Modalities and Frequencies of Physical Exercise on Glucose Control in People with Prediabetes (GLYCEX Randomised Trial). Galmes-Panades, AM., Bennasar-Veny, M., Oliver, P., et al.[2022]

A systematic review of 47 studies involving over 8000 individuals with prediabetes or diabetes found that while there are some risks associated with increased physical activity, such as musculoskeletal injuries and hypoglycemia, the overall prevalence of severe adverse events is low.

The review supports that increased physical activity is generally safe for individuals with prediabetes and diabetes, and it led to the development of a new risk assessment algorithm to help guide safe exercise practices for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence-based risk assessment and recommendations for physical activity clearance: diabetes mellitus and related comorbidities. Riddell, MC., Burr, J.[2022]

A pilot study involving non-diabetic individuals and a subject with Insulin Dependent Diabetes Mellitus (IDDM) showed that exercising in the morning led to a rapid decrease in blood glucose levels for non-diabetics, while evening exercise resulted in less decline and quicker recovery.

For the diabetic subject, morning exercise did not lower glucose levels and instead caused an increase after 40 minutes, suggesting that the timing of exercise may significantly impact glucose control in individuals with diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronobiology of exercise: the influence of scheduling upon glycemic responses of control and of subjects with diabetes mellitus. Cardoso, SS., Feuers, RJ., Tsai, TH., et al.[2011]

Exercise timing can influence the skeletal muscle clock, which is crucial for regulating metabolism and may help improve conditions like type 2 diabetes.

Disruptions in the skeletal muscle clock are linked to an increased risk of type 2 diabetes, suggesting that strategically timed exercise could serve as a therapeutic approach to enhance metabolic health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Time for Exercise? Exercise and Its Influence on the Skeletal Muscle Clock. Martin, RA., Esser, KA.[2023]

Postmeal exercise is more effective than premeal exercise for managing blood sugar levels in diabetes patients, as it allows the body to use glucose from the meal as fuel during physical activity.

The optimal time to start moderate-intensity exercise is about 30 minutes after a meal, as this timing helps to lower the peak in blood sugar levels that occurs after eating.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Why exercise before breakfast may not be for diabetes patients. Chacko, E.[2015]

A 12-week study involving 100 adults with overweight or obesity showed that both morning and evening exercise significantly increased daily physical activity by about 12-22 minutes compared to baseline.

Participants in both exercise groups also reported improvements in their daily routines, including more sleep (up to 36 minutes) and less time spent on sedentary activities like watching TV or playing video games.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How do previously inactive individuals restructure their time to 'fit in' morning or evening exercise: a randomized controlled trial. Brooker, PG., Gomersall, SR., King, NA., et al.[2023]

In a study involving 11 men with type 2 diabetes, afternoon high-intensity interval training (HIIT) significantly reduced blood glucose levels compared to morning HIIT, which actually increased glucose levels after exercise.

The findings suggest that the timing of exercise is crucial for managing blood glucose in type 2 diabetes, with afternoon sessions being more effective, highlighting the need for further research on longer training regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Afternoon exercise is more efficacious than morning exercise at improving blood glucose levels in individuals with type 2 diabetes: a randomised crossover trial. Savikj, M., Gabriel, BM., Alm, PS., et al.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

Temporal optimization of exercise to lower fasting glucose levels. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Effect of exercises according to the circadian rhythm in type 2 diabetes: Parallel-group, single-blind, crossover study. [2022]

3. Japan pubmed.ncbi.nlm.nih.gov

β-Cell function and body mass index are predictors of exercise response in elderly patients with prediabetes. [2022]

4. 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]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy of Different Modalities and Frequencies of Physical Exercise on Glucose Control in People with Prediabetes (GLYCEX Randomised Trial). [2022]

6. Canada pubmed.ncbi.nlm.nih.gov

Evidence-based risk assessment and recommendations for physical activity clearance: diabetes mellitus and related comorbidities. [2022]

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

Chronobiology of exercise: the influence of scheduling upon glycemic responses of control and of subjects with diabetes mellitus. [2011]

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

Time for Exercise? Exercise and Its Influence on the Skeletal Muscle Clock. [2023]

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

Why exercise before breakfast may not be for diabetes patients. [2015]

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

How do previously inactive individuals restructure their time to 'fit in' morning or evening exercise: a randomized controlled trial. [2023]

11. Germany pubmed.ncbi.nlm.nih.gov

Afternoon exercise is more efficacious than morning exercise at improving blood glucose levels in individuals with type 2 diabetes: a randomised crossover trial. [2020]