Diabetes Mellitus, Type 2, Insulin Resistance
Conditions
Keywords
Circadian Rhythm
Brief summary
This study evaluates the existence of a day-night rhythm in skeletal muscle energy metabolism in healthy lean 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 disobeying our normal day-night rhythm negatively influences our 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 under the influence of a day-night rhythm. The main objective of this study is to investigate the presence of a day-night rhythm in skeletal muscle energy metabolism (in particular mitochondrial function) of healthy young participants. Therefore, subjects will stay at the research unit for 44 hours, with standardized meals and sleeping time. During this period we will take five muscle biopsies, perform indirect calorimetry measurements and blood draws.
Interventions
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.
Sponsors
Maastricht University Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
* Caucasian * Healthy (as determined by dependent physician based on medical questionnaire) * Male * Age: 18-35 years * Normal BMI (18-25 kg/m2) * Regular sleeping time (normally 7-9h daily)
Exclusion criteria
* Extreme early bird or extreme night person (score ≤30 or ≥70 on MEQ-SA questionnaire) * Heavily varying sleep-wake rhythm * Shiftwork during last 3 months * Travel across \>1 time zone in the last 3 months * Engagement in exercise \> 2 hours total per week * Using \>400mg caffeine daily * Smoking * Unstable body weight (weight gain or loss \> 3kg in the last 3 months) * Significant food allergies/intolerance (seriously hampering study meals) * Participation in another biomedical study within 1 month before the first study visit * Any contra-indication to Magnetic Resonance Imaging (MRI) scanning
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Day-night rhythm in skeletal muscle mitochondrial respiration | 40 hours. | O2-flux (pmol/mg/s) measured with high resolution respirometry upon administration of different substrates |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Day-night rhythm in whole-body energy metabolism | 40 hours. | Energy expenditure (kJ/min), glucose oxidation (g/min) and fat oxidation (g/min) measured by indirect calorimetry |
| Day-night rhythm in muscle DNA, mRNA and protein levels of markers involved in molecular clock and mitochondrial metabolism. | 40 hours. | Quantify mRNA and protein levels by qPCR or micro-array and Western blots |
| Day-night rhythm of in markers of normal day-night rhythm (cortisol, melatonin, core body temperature) | measured during the 2nd study day | Blood cortisol and melatonin levels and core body temperature measured by an ingested telemetric pill. |
| Day-night rhythm in blood metabolic compounds (e.g. glucose, insulin, FFA's, cholesterol) | measured during the 2nd study day | — |
| Day-night rhythm of molecular clock mRNA and protein levels in blood PBMC's | measured during the 2nd study day | Measured by qPCR and Western Blots |
| Change in liver volume and liver lipid concentration during the day | First study day 6 PM, second study day 7 AM | Measured by Magnetic Resonance Imaging and -Spectroscopy (MRI/MRS). Lipid signals in the MRS spectra will be quantified while suppressing the strong water signal in the region of interest (right liver lobe) |
Countries
Netherlands
Outcome results
None listed