Exercise to Restore 24h Rhythms in Metabolism (RESTORE)

Maastricht University

Status: Completed

Conditions: Insulin Resistance; Diabetes Mellitus, Type 2

Treatments: Behavioral: High-intensity interval training

Study type: Interventional

Funder types: Other

Identifiers

NCT04565418

NL73834.068.20

Details and patient eligibility

About

This study will investigate the effect of exercise training on 24h rhythms in substrate metabolism in overweight subjects with impaired glucose tolerance. Subjects will perform exercise training for 12 weeks. Before and after the exercise period, they will be admitted to research facilities for 45 hours to assess 24h rhythms in substrate metabolism. In a single-arm longitudinal design, subjects will serve as their own control.

Full description

Recent evidence shows that pre-diabetes is characterized by marked alterations in 24h substrate metabolism, indicating metabolic inflexibility with an inability to fully switch to fat oxidation during the night. Whereas exercise has been shown to promote mitochondrial function and insulin sensitivity, it is unknown to if exercise training is able to restore 24h rhythmicity in overall substrate metabolism and muscle metabolism in human subjects with pre-diabetes.

In this single-arm longitudinal design, subjects will serve as their own control. Subjects will perform high-intensity interval training for 12 weeks (3x times per week) on a cycle ergometer at the research facility. Pre and post exercise, subjects will stay in a metabolic chamber and adhere to a relatively normal life-style in order to standardize the main 24h measurement period. As the primary outcome, substrate metabolism will be measured with a ventilated hood system and by indirect calorimetry in the chambers. Muscle biopsies from the vastus lateralis and frequent blood samples will also be taken over the course of the 24h. Thereby, ex-vivo skeletal muscle mitochondrial function and muscle clock gene expression will serve as the main secondary outcomes.

Enrollment: 10 patients

Sex: Male

Ages: 40 to 75 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Caucasian

• Healthy (as determined by dependent physician)

• Overweight: BMI 25 - 35 kg/m2

• Prediabetic based on one or a combination of the following criteria:

  • Impaired Glucose Tolerance (IGT): plasma glucose values ≥ 7.8 mmol/l and ≤ 11.1 mmol/l 120 minutes after glucose drink consumption during OGTT in screening.
  • Impaired Fasting Glucose (IFG): Fasting plasma glucose ≥ 6.1 mmol/l and ≤ 6.9 mmol/l.
  • Insulin Resistance: glucose clearance rate ≤ 360ml/kg/min, as determined using the OGIS120 model.
  • HbA1c of 5.7-6.4%.

• Regular sleeping time (normally 7 - 9h daily)

• Stable dietary habits: no weight gain or loss > 3kg in the last three months.

Exclusion criteria

• Use of anticoagulants
• Previously diagnosed with type 2 diabetes
• Current alcohol consumption > 20 grams alcohol/day
• Extreme early bird or extreme night person (score ≤ 30 or ≥ 70 on MEQ-SA questionnaire)
• Heavily varying sleep-wake rhythm
• Nightshift work during last 3 months
• Travel across > 1 time zone in the last 3 months
• Significant food allergies/intolerance (seriously hampering study meals)
• Using > 400mg caffeine daily (more than 4 coffee or energy drink)
• Smoking

Trial design

Primary purpose: Basic Science

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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10 participants in 1 patient group

Exercise training

Experimental group

Description:

12 week high-intensity interval training (3 sessions per week): Before and after exercise, subjects are kept at the research facility to adhere to a standardized living protocol, mimicking a normal daily living situation. During the study, multiple tests will be performed, including muscle biopsies, blood draws and indirect calorimetry.

Treatment:

Behavioral: High-intensity interval training