Diabetes Mellitus, Type 2, Insulin Resistance
Conditions
Keywords
Circadian Rhythm, Circadian Misalignment, Insulin Sensitivity
Brief summary
This study will evaluate the effect of circadian misalignment on insulin sensitivity in healthy lean subjects in a randomized cross-over design. Subjects will be admitted to the research facility for two study periods of 3 and 3.5 days. In one of the study periods, the behavioral cycle will be shifted by 12 hours. Insulin sensitivity will be measured with a hyperinsulinemic euglycemic clamp.
Detailed description
Recent evidence shows that misalignment of the circadian rhythm (e.g. by rotating shift work) impairs glucose metabolism markedly, possibly by decreasing insulin sensitivity in peripheral tissues and liver. Nowadays our society is indispensably connected to a lifestyle that allows wakefulness at every time of the 24 hours cycle. Social jetlag is a phenomenon that affects a large part of the general population, thus circadian misalignment extends far beyond those who are on a shift work schedule. Therefore, decreased insulin sensitivity in individuals affected by circadian misalignment may help to explain the increased prevalence of T2DM in night shift workers that has been found in epidemiological studies. The study is an interventional randomized crossover trial in which each subject serves as it owns control. For the study, the investigators ask the subjects to participate in two study periods, one of 3 days length (control condition) and the other of 3.5 days length (misalignment condition). During the 3.5 day misalignment condition, subjects will shift their day-night rhythm by 12 hours, which will lead to maximal circadian misalignment. Insulin sensitivity will be measured by a hyperinsulinemic euglycemic clamp. Secondary parameters will include ex-vivo skeletal muscle mitochondrial function and whole-body energy metabolism.
Interventions
BEHAVIORALCircadian Misalignment
Sponsors
Maastricht University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
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) * Habitual bedtime at 11 PM ± 2 hours
Exclusion criteria
* Extreme early bird or extreme night person * Heavily varying sleep-wake rhythm * Shiftwork during last 3 months * Travel across \>1 time zone in the last 3 months * Engagement in exercise \> 3 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 * Claustrophobia * Medication use hampering the study (as determined by responsible physician) * Recent blood donation. * Any contra-indication to the telemetric pill: * Any acute condition, exacerbation of chronic condition, or medical history that would in the investigator's opinion interfere with the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Insulin Sensitivity | 2 days after circadian misalignment and matched time in control arm. | Measured with hyperinsulinemic euglycemic clamp |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Non-oxidative glucose disposal | 2 days after circadian misalignment and matched time in control arm. | — |
| Skeletal muscle mitochondrial function | 1 and 2 days after circadian misalignment and matched times in control arm | Measured with high-resolution respirometry on permeabilized muscle fibers after muscle biopsy |
| Whole body energy metabolism while awake | 1 and 2 days after circadian misalignment and matched times in control arm | Measured by indirect calorimetry |
| Sleeping metabolic rate | 1.5 days after circadian misalignment and matched time in control arm | Measured by indirect calorimetry |
| Skeletal muscle mtDNA | 1 and 2 days after circadian misalignment and matched times in control arm | Measured by qPCR |
| Skeletal muscle mRNA | 1 and 2 days after circadian misalignment and matched times in control arm | Measured by qPCR and Western Blotting |
| Oxidative glucose disposal | 2 days after circadian misalignment and matched time in control arm. | — |
| Metabolic compounds in the blood (e.g. glucose, insulin, FFA's, Triglycerides, cholesterol) | 1 and 2 days after circadian misalignment and matched times in control arm | — |
| Core-body-temperature | 1 day after circadian misalignment and matched time in control arm | Measured by a telemetric pill |
| Peripheral skin temperature | 1 day after circadian misalignment and matched time in control arm | Measured by skin temperature sensors |
| Central skin temperature | 1 day after circadian misalignment and matched time in control arm | Measured by skin temperature sensors |
| Heart rate | 1 day after circadian misalignment and matched time in control arm | Measured by heart rate monitor |
| Skeletal muscle proteins | 1 and 2 days after circadian misalignment and matched times in control arm | Measured by Western Blotting |
Countries
Netherlands
Outcome results
None listed