Circadian Rhythm and Metabolic Effects of Exercise

NCT05115682 | Completed

• 1 other identifier: HIT Metabolome
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Diabetes Mellitus, Type 2; Circadian Rhythm; Glycemic Control

Keywords

Type 2 Diabetes; High-intensity Intermittent Exercise; Circadian Rhythm; Glycemic Control; Energy Metabolism

Outcome Measures

Primary Outcomes (1)

• 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.

  3 days (1 day before to 1 day after exercise)

Secondary Outcomes (6)

• Acute Exercise-induced Changes in Interstitial Glucose Concentration

  2 hours (0 minutes before to 120 minutes after exercise)

• Interstitial Glucose Concentration Response to a Meal

  2 days (1 day before and day of exercise)

• Interstitial Glucose Concentration Variability

  3 days (1 day before to 1 day after exercise)

• Time Spent in Interstitial Glucose Concentration Range

  3 days (1 day before to 1 day after exercise)

• Nocturnal Interestitial Glucose Concentration

  2 days (day of, and 1 day after exercise)

Study Arms (2)

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.

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.

Behavioral: High-intensity Intermittent Exercise

Interventions

High-intensity Intermittent Exercise BEHAVIORAL

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).

Afternoon First; Morning First

Eligibility Criteria

• Age: 45 Years - 68 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Medications: Insulin
• 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

Sponsors & Collaborators

• Karolinska Institutet: lead
• Karolinska University Hospital: collaborator

Study Sites (1)

Karolinska Institutet

Stockholm, 17177, Sweden

Location

Related Publications (1)

• 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.

  PMID: 40580209 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

High-Intensity Interval Training

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Physical Conditioning, Human; Exercise; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Harriet Wallberg-Henriksson, MD PhD

  Karolinska Institutet

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. MD PhD

Model Details: 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.

Study Record Dates

• First Submitted: October 19, 2021
• First Posted: November 10, 2021
• Study Start: November 10, 2021
• Primary Completion: June 25, 2024
• Study Completion: June 25, 2024
• Last Updated: February 21, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Time Frame: Data will be made available indefinetly after publication.
• Access Criteria: Data will be available for any purpose.

Locations

SE (1)