Acute Timed Exercise and 24h Metabolism (TIM)

Timed Exercise to Acutely Improve Energy and Substrate Metabolism at Night in Men and Women With Prediabetes

The primary objective of this randomized controlled cross-over study is to investigate if an acute, glycogen lowering exercise bout performed either in the morning or late afternoon differentially affects the respiratory exchange ratio at night in men and women with prediabetes. For this purpose, participants will stay in a respiration chamber and will be subjected to either an exercise bout in the morning or late afternoon.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes; Overweight and Obesity
• Intervention / Treatment: Behavioral: Timing of exercise; Behavioral: Control

Detailed Description

Appropriate timing of lifestyle interventions may facilitate healthy rhythmicity in metabolism and optimize the effectiveness of such interventions in improving metabolic health. In this context, 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). In addition, exercise may also have beneficial effects on the immune response that is known to impact on insulin sensitivity and overall metabolic health. In this study it is hypothesized that exercise performed at different times of the day exerts a differential effect on 24h metabolism in people at risk for developing T2D. To test this, a randomized controlled cross-over study is conducted in which participants are subjected to either an exercise in the morning or late afternoon while staying in the respiration chamber. Main outcome is substrate utilization during the night as measured with the respiration chamber, but 24-hrs blood draws will also be performed to examine effect of exercise on circulating metabolites.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Limburg
    • Maastricht, Limburg, Netherlands, 6229 ER
      • Maastricht University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Signed informed consent
• Healthy (determined by dependent physician)
• Man or post-menopausal woman
• Age between 50 - 75 years
• BMI ≥ 25 kg/m2
• Pre-diabetes based on meeting at least one of the following criteria: impaired glucose tolerance defined as plasma glucose values ≥ 7.8 mmol/l and ≤ 11.1 mmol/l 120 minutes after glucose drink consumption during oral glucose tolerance test in screening, impaired fasting glucose defined as fasting plasma glucose ≥ 6.1 mmol/l and ≤ 6.9 mmol/l, insulin resistance defined as a glucose clearance rate ≤ 360 mL/kg/min as determined using OGIS120, HbA1c of 5.7-6.4%
• Regular sleeping habits (7 - 9h of daily sleep)
• Stable diet and weight: No weight gain or loss > 3kg in the last three months

Exclusion Criteria:

• Not meeting all inclusion criteria
• Fasting plasma glucose
• ≥ 7.0 mmol/L
• Hemoglobin < 7.8 mmol/L
• Previously diagnosed with type 2 diabetes
• Uncontrolled hypertension
• In case of an abnormal electrocardiogram at rest: this will be discussed with the responsible medical doctor
• Subjects who do not want to be informed about unexpected medical findings during the screening /study, or do not wish that their physician is informed
• Any contra-indication to the Equivital telemetric pill
• Hypomotility disorders of the gastro-intestinal tract
• Extreme early bird or extreme night person (score ≤30 or ≥70 on morning-eveningness questionnaire self assessment)
• Heavily varying sleep-wake rhythm
• Night shift work during last 3 months
• Travel across > 1 time zone in the last 3 months
• Frequent engagement in programmed exercise as judged by the investigator
• Significant food allergies/intolerance (seriously hampering study meals)
• Participation in another biomedical study within 1 month before the first study visit
• Using > 400mg caffeine daily (more than 4 cups of coffee or energy drinks)
• Smoking
• Any acute condition, exacerbation of chronic condition, or medical history that would in the investigator's opinion interfere with the study
• Antecubital veins that present tremendous difficulty in obtaining frequent blood draws (e.g. too small)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control	Behavioral: Control; No exercise
Experimental: AM exercise	Behavioral: Timing of exercise; An acute exercise bout of cycling performed in the morning at 9 AM or at 5 PM
Experimental: PM exercise	Behavioral: Timing of exercise; An acute exercise bout of cycling performed in the morning at 9 AM or at 5 PM

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nocturnal respiratory exchange ratio	Relative carbohydrate/fat oxidation during the night	35 hours respiration chamber stay per intervention arm

Secondary Outcome Measures

Outcome Measure	Time Frame
24 hour energy and substrate metabolism determined using oxygen and carbondioxide levels as measured with whole-chamber respirometry	35 hours respiration chamber stay per intervention arm
Immune cell phenotypes determined using blood samples obtained during the interventions	35 hours respiration chamber stay per intervention arm
Blood glucose levels following the exercise intervention measured continuously using a continuous glucose monitor device	7 days post the exercise intervention

Other Outcome Measures

Outcome Measure	Time Frame
Diurnal variation in circulating glucoregulatory hormones (e.g. insulin) analysed in blood samples obtained throughout the day	35 hours respiration chamber stay per intervention arm
Feet sensitivity based on score on a neuropathy questionnaire	Baseline visit
Diurnal variation in metabolite levels (e.g. glucose, free fatty acids) analysed in blood samples obtained throughout the day	35 hours respiration chamber stay per intervention arm
Diurnal variation in core body temperature using a core temperature pill that measures 24hrs	35 hours respiration chamber stay per intervention arm
Feet sensitivity based on a clinical foot assessment	Baseline visit

Collaborators and Investigators

• Sponsor: Maastricht University
• Investigators: Principal Investigator: Joris Hoeks, Dr, Maastricht University

Study record dates

Study Major Dates

• Study Start (Actual): March 16, 2022
• Primary Completion (Actual): November 21, 2024
• Study Completion (Actual): November 21, 2024

Study Registration Dates

• First Submitted: August 25, 2021
• First Submitted That Met QC Criteria: October 6, 2021
• First Posted (Actual): October 11, 2021

Study Record Updates

• Last Update Posted (Actual): June 13, 2025
• Last Update Submitted That Met QC Criteria: June 10, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Exercise; Metabolism; Metabolic flexibility; Day-night rhythm; Glycogen
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Overweight
• Other Study ID Numbers: NL78628.068.21

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Participant data will only discussed with other researcher on group level. We are not interested in individual participant data

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No