Skip to main content
OpenTrials
Completed

NCT Number: NCT03733743

Day-night Rhythm in Muscle Metabolism of Prediabetics

This study evaluates the existence of a day-night rhythm in skeletal muscle energy metabolism in prediabetic subjects. Subjects will stay at the research facility for 44 hours with a standardized living protocol during which several measurements of skeletal muscle and whole body energy metabolism will be performed.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Diabetes Mellitus, Type 2 Diabetes Mellitus Endocrine System Diseases Glucose Metabolism Disorders Hyperinsulinism Insulin Resistance Metabolic Diseases Nutritional and Metabolic Diseases

Age range

40 year–75 year

Sex eligibility

Male

Study type

Interventional

Phase

Not applicable

Primary location

Maastricht University

Maastricht, Limburg, 6229 ER, Netherlands

About this study

Recent evidence from both observational and experimental studies indicates that disobedience of a normal day-night rhythm negatively influences metabolic and cardiovascular health, possibly leading to obesity and type 2 diabetes mellitus (T2DM). An important hallmark of obesity and T2DM is a decreased skeletal muscle mitochondrial function. Interestingly, recent research indicates that also skeletal muscle mitochondrial function is under the influence of a day-night rhythm. In this study, the presence of a day-night rhythm in skeletal muscle energy metabolism (in particular mitochondrial function) of overweight prediabetic participants will be investigated. During this study, subjects will stay at the research unit for 44 hours, with standardized meals and sleeping time. Five muscle biopsies (v. lateralis) and frequent blood draws will be taken. In addition, indirect calorimetry measurements will be performed.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Standardized living protocol

Other

Subjects stay at the research facility for 44 hours and adhere to a standard sleeping, eating and activity protocol. During this protocol, multiple measurements will be performed including skeletal muscle biopsies (m. vastus lateralis), blood draws, indirect calorimetry and MRS measurements.

Primary outcomes

  1. Day-night rhythm in skeletal muscle mitochondrial respiration

    Time frame: measured on day two at 8:00, 13:00, 18:00, 23:00, 04:00

    O2-flux (pmol/mg/s) measured with high resolution respirometry

Secondary outcomes

  1. Day-night rhythm in whole-body energy metabolism (energy expenditure)

    Time frame: measured on day two at 8:00, 13:00, 18:00, 23:00, 04:00

    Energy expenditure (kJ/min) measured by indirect calorimetry

  2. Day-night rhythm in whole-body energy metabolism (glucose oxidation)

    Time frame: measured on day two at 8:00, 13:00, 18:00, 23:00, 04:00

    glucose oxidation (g/min) measured by indirect calorimetry

  3. Day-night rhythm in whole-body energy metabolism (fat oxidation)

    Time frame: measured on day two at 8:00, 13:00, 18:00, 23:00, 04:00

    fat oxidation (g/min) measured by indirect calorimetry

  4. Day-night rhythm in muscle protein levels of markers involved in molecular clock and mitochondrial metabolism.

    Time frame: measured on day two at 8:00, 13:00, 18:00, 23:00, 04:00

    Quantify protein levels by Western blots

  5. Day-night rhythm in muscle DNA of markers involved in molecular clock and mitochondrial metabolism.

    Time frame: measured on day two at 8:00, 13:00, 18:00, 23:00, 04:00

    Quantify DNA by qPCR

  6. Day-night rhythm in muscle DNA involved in molecular clock and mitochondrial metabolism.

    Time frame: measured on day two at 8:00, 13:00, 18:00, 23:00, 04:00

    Quantify DNA by micro-array

  7. Day-night rhythm in muscle mRNA markers involved in molecular clock and mitochondrial metabolism.

    Time frame: measured on day two at 8:00, 13:00, 18:00, 23:00, 04:00

    Quantify mRNA levels by micro array

  8. Day-night rhythm of markers of normal day-night rhythm (cortisol)

    Time frame: measured on day two, every two hours for 24 hours beginning at 08:00

    Blood cortisol levels

  9. Day-night rhythm of in markers of normal day-night rhythm (core body temperature)

    Time frame: measured continuously for 24 hours on day two

    Core body temperature measured by an ingested telemetric pill.

  10. Day-night rhythm of in markers of normal day-night rhythm (melatonin)

    Time frame: measured on day two, every two hours for 24 hours beginning at 08:00

    Blood melatonin levels.

  11. Day-night rhythm in serum glucose

    Time frame: measured on day two, every two hours for 24 hours beginning at 08:00

    Serum glucose levels determined from venous blood draws

  12. Day-night rhythm in serum insulin

    Time frame: measured on day two, every two hours for 24 hours beginning at 08:00

    Serum insulin levels determined from venous blood draws

  13. Day-night rhythm in serum free fatty acids (FFA)

    Time frame: measured on day two, every two hours for 24 hours beginning at 08:00

    Serum FFA levels determined from venous blood draws

  14. Day-night rhythm in serum triglycerides

    Time frame: measured on day two, every two hours for 24 hours beginning at 08:00

    Serum triglyceride levels determined from venous blood draws

  15. Day-night rhythm in serum cholesterol

    Time frame: measured on day two, every two hours for 24 hours beginning at 08:00

    Serum cholesterol levels determined from venous blood draws

  16. Change in energy status of the heart between morning and evening

    Time frame: Measured on first study day 5:30 PM (duration 45 minutes), second study day 7:30 AM (duration 45 minutes)

    variation in phosphorus metabolites measured by Magnetic Resonance Imaging and - Spectroscopy (MRI/MRS)

Sponsors and collaborators

Lead sponsor

Maastricht University

Other

Collaborators

  • Maastricht University Medical Center

Registry information

Official study title

Day-night Rhythm in Muscle Metabolism of Prediabetic Subjects

Important dates

Study start
2018
Primary completion
2019
Study completion
2019
First posted
Nov 7, 2018
Registry last updated
Aug 16, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.