Exercise Timing and the Circadian Clock in Individuals With Type 2 Diabetes and Those at Risk

NCT06136013 | Unknown

• 1 other identifier: EX-TIMING_2023
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

Many investigations have been done to determine the exercise that can elicit the greatest benefits on glycemic control and metabolic health, with findings suggesting that incorporation of higher intensity and longer duration of exercise prescribed may eliminate much of the "non-response" observed following exercise training. Even with the incorporation of higher intensity exercise into interventions aimed at improving glycemic control in individuals with type 2 diabetes mellitus (T2DM), the investigators and others continue to have mixed results, with not all individuals with T2DM obtaining benefits in insulin sensitivity and glycemic control to a given exercise training program. Many of the metabolic processes involved in glucose homeostasis, such as insulin production and sensitivity, undergo daily circadian rhythms, controlled by cellular clock machinery located both centrally and peripherally (i.e. skeletal muscle). However, in adults with T2DM, these diurnal rhythms are impaired, with reduced insulin sensitivity in the morning, which is thought to contribute to the fasting hyperglycemia (i.e., "dawn phenomenon") observed in these individuals. Exercise may be a non-photic cue that can amplify or alter these metabolic rhythms. It has been suggested that skeletal muscle metabolic inflexibility in metabolic disorders such as overweight/obesity and T2DM is associated with reduced mitochondrial fatty acid oxidative capacity. It has been demonstrated that exercise can increase mitochondrial oxidative capacity by remodeling mitochondrial morphology and dynamics. It is unknown if potential differences in metabolic flexibility can be found in response to exercise at different times of the day. Most of the experimental evidence originates from animal models with only 3 studies performed in humans with T2DM, which displayed conflicting results. To overcome the shortcomings in the literature, the main objective of this research project is to assess the effects of performing exercise at different times of the day on glycemic control and related outcomes on the inter-individual response variability in glycemic control and related metabolic health parameters in two distinct populations: 1) individuals with T2DM on the most common mono-hyperglycemic drug therapy (i.e., metformin); and 2) age-matched sedentary overweight/obese individuals, where glycemic control is known to deteriorate, hence increasing the risk of developing insulin resistance and T2DM.

Conditions

Diabetes Mellitus, Type 2

Keywords

Exercise; Diabetes Mellitus Type 2; Glycemic Control; Inter-individual variability; Aging; Obesity

Outcome Measures

Primary Outcomes (1)

• Changes in 24-hour area under cover (AUC) glucose from baseline to 1, 2, and 3 months

  Assess differences in 24-hour area under cover (AUC) glucose at different exercise times (i.e. morning, afternoon and evening) separately for individuals with T2DM and age-matched overweight/obese older adults.

  3 months

Secondary Outcomes (12)

• Changes in body mass index (BMI) from baseline to 1, 2, and 3 months

  3 months

• Changes in bone mineral density from baseline to 1, 2, and 3 months

  3 months

• Changes in fat and lean body mass from baseline to 1, 2, and 3 months

  3 months

• Changes in resting metabolic rate (RMR) from baseline to 1, 2, and 3 months

  3 months

• Changes in respiratory quotient from baseline to 1, 2, and 3 months

  3 months

Study Arms (3)

Morning HIIT 30-min following breakfast between 9:00 to 10:00 am.

EXPERIMENTAL

The exercise prescription will be standardized according to body weight and based on physical activity guidelines to achieve a weekly target of 10 kcal/kg. The duration of the exercise sessions will be based on the weekly target for energy expenditure, considering weight and individual VO2peak and will be updated at the beginning of each intervention block.

Behavioral: HIIT

Afternoon HIIT 30-min following lunch between 2:00 to 3:00 pm.

EXPERIMENTAL

The exercise prescription will be standardized according to body weight and based on physical activity guidelines to achieve a weekly target of 10 kcal/kg. The duration of the exercise sessions will be based on the weekly target for energy expenditure, considering weight and individual VO2peak and will be updated at the beginning of each intervention block.

Behavioral: HIIT

Evening HIIT 30-min following dinner between 7:00 to 8:00 pm.

EXPERIMENTAL

The exercise prescription will be standardized according to body weight and based on physical activity guidelines to achieve a weekly target of 10 kcal/kg. The duration of the exercise sessions will be based on the weekly target for energy expenditure, considering weight and individual VO2peak and will be updated at the beginning of each intervention block.

Behavioral: HIIT

Interventions

HIIT BEHAVIORAL

1 minute of exercise at 90% of their PPO, followed by a 1-minute rest at 40-60% of their peak power output using a cycle ergometer.

Afternoon HIIT 30-min following lunch between 2:00 to 3:00 pm.; Evening HIIT 30-min following dinner between 7:00 to 8:00 pm.; Morning HIIT 30-min following breakfast between 9:00 to 10:00 am.

Eligibility Criteria

• Age: 55 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• previous diagnosis of T2DM
• currently taking metformin (Group 1 only);
• Adults aged 55 to 75 years
• Physically inactive people (i.e. with less than 20 minutes per day of exercise, maximum 3 days per week)

You may not qualify if:

• Use of exogenous insulin and taking any other antihyperglycemic medication beyond metformin
• having major micro- or macro-vascular complications from T2DM
• History of cardiovascular incidents
• People with motor limitations (musculoskeletal or neurological) that limit the practice of physical exercise
• inability to provide informed consent
• BMI ≥25 without diagnosis of T2DM
• Adults aged 55 to 75 years
• Physically inactive people (i.e. with less than 20 minutes per day of exercise, maximum 3 days per week)
• History of cardiovascular incidents
• People with motor limitations (musculoskeletal or neurological) that limit the practice of physical exercise
• inability to provide informed consent

Sponsors & Collaborators

• Faculdade de Motricidade Humana: lead
• Fundação para a Ciência e a Tecnologia: collaborator

Study Sites (1)

Faculdade de Motricidade Humana

Cruz Quebrada, Oeiras, 1409-002, Portugal

Location

Related Publications (1)

• Magalhaes JP, Oliveira EC, Hetherington-Rauth M, Jesus F, Rodrigues MC, Raposo JF, Ribeiro RT, Caetano C, Sardinha LB. The Ex-Timing trial: evaluating morning, afternoon, and evening exercise on the circadian clock in individuals with type 2 diabetes and overweight/obesity-a randomized crossover study protocol. Trials. 2024 Aug 6;25(1):526. doi: 10.1186/s13063-024-08335-y.

  PMID: 39107793 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Motor Activity; Obesity

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Behavior; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• João B Magalhães, PhD

  Faculdade de Motricidade Humana - Universidade de Lisboa

  PRINCIPAL INVESTIGATOR

Central Study Contacts

João B Magalhães, PhD

CONTACT

214 149 241; joaomagalhaes@fmh.ulisboa.pt

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This project will consist of a randomized cross-over exercise intervention involving 2 groups: Group 1, individuals with T2DM; Group 2, age-matched older adults with overweight/obesity. Each study will consist of 3, 2-week blocks of 3 days per week of supervised post-prandial exercise using high-intensity interval training (HIIT). Between each training block, a 2-week washout period, where participants avoid structured exercise, will take place. This has been shown to be enough time to eliminate any exercise effects on insulin sensitivity and glycemic control. The cross-over groups are the following: 1. morning HIIT. 2. afternoon HIIT. 3. evening HIIT. Each participant will serve as their own control, helping to account for the biological variability within the individual, as well as their individual chronotype, such as sleep/wake cycles. Participants will be randomly selected to a block order.

Study Record Dates

• First Submitted: July 26, 2023
• First Posted: November 18, 2023
• Study Start: January 1, 2024
• Primary Completion: July 1, 2024
• Study Completion: December 1, 2024
• Last Updated: November 18, 2023

Record last verified: 2023-11

Locations

PT (1)