Day-night Rhythm in Muscle Metabolism of Prediabetics
- Conditions
- Diabetes Mellitus, Type 2Insulin Resistance
- Interventions
- Other: Standardized living protocol
- Registration Number
- NCT03733743
- Lead Sponsor
- Maastricht University
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 12
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Standardized living protocol Standardized living protocol 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, MRS measurements and indirect calorimetry.
- Primary Outcome Measures
Name Time Method Day-night rhythm in skeletal muscle mitochondrial respiration 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 Outcome Measures
Name Time Method Day-night rhythm in muscle DNA of markers involved in molecular clock and mitochondrial metabolism. measured on day two at 8:00, 13:00, 18:00, 23:00, 04:00 Quantify DNA by qPCR
Day-night rhythm in muscle mRNA markers involved in molecular clock and mitochondrial metabolism. measured on day two at 8:00, 13:00, 18:00, 23:00, 04:00 Quantify mRNA levels by micro array
Day-night rhythm of markers of normal day-night rhythm (cortisol) measured on day two, every two hours for 24 hours beginning at 08:00 Blood cortisol levels
Day-night rhythm in whole-body energy metabolism (energy expenditure) measured on day two at 8:00, 13:00, 18:00, 23:00, 04:00 Energy expenditure (kJ/min) measured by indirect calorimetry
Day-night rhythm in serum free fatty acids (FFA) measured on day two, every two hours for 24 hours beginning at 08:00 Serum FFA levels determined from venous blood draws
Day-night rhythm in whole-body energy metabolism (glucose oxidation) measured on day two at 8:00, 13:00, 18:00, 23:00, 04:00 glucose oxidation (g/min) measured by indirect calorimetry
Day-night rhythm in muscle DNA involved in molecular clock and mitochondrial metabolism. measured on day two at 8:00, 13:00, 18:00, 23:00, 04:00 Quantify DNA by micro-array
Day-night rhythm of in markers of normal day-night rhythm (melatonin) measured on day two, every two hours for 24 hours beginning at 08:00 Blood melatonin levels.
Day-night rhythm in serum triglycerides measured on day two, every two hours for 24 hours beginning at 08:00 Serum triglyceride levels determined from venous blood draws
Day-night rhythm in serum cholesterol measured on day two, every two hours for 24 hours beginning at 08:00 Serum cholesterol levels determined from venous blood draws
Change in energy status of the heart between morning and evening 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)
Day-night rhythm in whole-body energy metabolism (fat oxidation) measured on day two at 8:00, 13:00, 18:00, 23:00, 04:00 fat oxidation (g/min) measured by indirect calorimetry
Day-night rhythm in muscle protein levels of markers involved in molecular clock and mitochondrial metabolism. measured on day two at 8:00, 13:00, 18:00, 23:00, 04:00 Quantify protein levels by Western blots
Day-night rhythm in serum glucose measured on day two, every two hours for 24 hours beginning at 08:00 Serum glucose levels determined from venous blood draws
Day-night rhythm of in markers of normal day-night rhythm (core body temperature) measured continuously for 24 hours on day two Core body temperature measured by an ingested telemetric pill.
Day-night rhythm in serum insulin measured on day two, every two hours for 24 hours beginning at 08:00 Serum insulin levels determined from venous blood draws
Trial Locations
- Locations (1)
Maastricht University
🇳🇱Maastricht, Limburg, Netherlands