Research Questions: Primary:1. Does a single night of short sleep reduce metabolic flexibility following a mixed meal challenge?2. Does a single night of short sleep alter the responsiveness of the HPA-axis?3. Are the disturbances of a single night…
ID
Source
Brief title
Condition
- Lipid metabolism disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primairy study parameters are:
- Lipid metabolism by measurement of hormone and lipid concentrations in plasma
in response to a mixed-meal challenge
- Energy metabolism by measurement of indirect calorimetry
- HPA-axis responsiveness by hormone and blood pressure measurement during a
cold- feet pressor test
- Mood via short questionnaires (Profile of Mood States)
Secondary outcome
The secondairy study parameters are:
- Gene expression profiles and metabolomics in muscle and fat tissue and plasma
- Gene expression profiles in skin and hair samples
Background summary
In modern daily life, incidental short sleep duration has become a common
feature. Chronic short sleep duration is associated with a many adverse health
effects, including metabolic disturbances such as obesity, type 2 diabetes and
cardiovascular diseases, as well as disturbances in the stress system, negative
mood and tissue ageing. These associations may be explained by metabolic
disturbances caused by repeated incidental short sleep duration. A single night
of partial sleep restriction of 4 hours sleep in healthy individuals acutely
induces insulin resistance with respect to glucose uptake. Furthermore, several
nights short sleep impairs intracellular insulin signalling in white fat.
Insulin is produced upon glucose availability and is a signal for tissues to
switch from fat oxidation (during fasting) to glucose oxidation. The ability to
switch between glucose and fat oxidation in response to insulin is called
metabolic flexibility. Short sleep may therefore impair metabolic flexibility,
predisposing to more insulin resistance.
Interestingly, insulin in the brain decreases the feedback of the
hypothalamus-pituitary-adrenal (HPA) axis, thereby contributing to an increased
cortisol response. Additionally, short sleep increases late afternoon cortisol
levels. Disturbances in the HPA-axis are in turn related to mood and downstream
effects on tissue aging as a result of cross-talk between the central HPA-axis
and local HPA-axis equivalents are also implicated. Study in mice shows that
cortisol produced by the central HPA-axis in response to chronic stress exerts
negative feedback on the local HPA-axis equivalent in skin resulting in
suppression of melanogenesis. Melanin production is an important defence
mechanism against UV irradiation and it*s tissue ageing effects. Taken these
data together, we hypothesize that short sleep reduces metabolic flexibility,
increases insulin resistance and thereby reduces HPA-reactivity. Furthermore,
we hypothesize short sleep will negatively affect mood and tissue ageing due to
dysregulation of the HPA-axis. Since a higher BMI is correlated with metabolic
inflexibility and insulin resistance, we hypothesize that higher BMI will
enlarge the effects of short sleep on metabolism, HPA-axis reactivity and
downstream effects.
Study objective
Research Questions:
Primary:
1. Does a single night of short sleep reduce metabolic flexibility following a
mixed meal challenge?
2. Does a single night of short sleep alter the responsiveness of the HPA-axis?
3. Are the disturbances of a single night of short sleep dependent on BMI?
Exploratory:
4. Does a single night of short sleep negatively affect mood and accelerate
tissue ageing?
5. Does a single night of short sleep disturb intracellular metabolic pathways
in fat and muscle tissue?
6. Does a single night of short sleep affect circadian rhythms hormone levels
and skin temperature?
Study design
We will investigate the effects of a single night of short sleep compared to
normal sleep in 36 participants within a BMI range from 20-35 kg/m2 in a
balanced cross-over intervention study.
Intervention
A single night of short sleep duration (4 hours) compared to a control
condition of normal sleep duration (8 hours).
Study burden and risks
The study is composed of three components: a single screeningsvisit, two times
a study day at our research facility and at-home measurements.
Time, Actions, Risks
Screening:
Time: ~ 1 hour.
Actions: height, weight, physical examination, bio-electrical impedance, 1
venapuncture.
Risks: local hematoma
Study day (2x):
Time: From 21.00 until 18.00 the following day, in our research unit.
Actions: intravenous catheter, short or normal sleep duration, two times
isocaloric liquid mixed meal, indirecte calorimetry, muscle, fat and skin
biopsy, hair samples, stress reactivity test.
Risks: local hematoma (from intravenous catheter), localized pain, swelling,
hematoma and small scar (from biopsies).Transient localized pain from hair
sampling. Transient physical discomfort from stress reactivity test (3 minutes
of cold feet and several blood pressure measurements).
In-home measurements
Time: during one week prior to study day: ~15 minutes daily en 3 times 30
mintues. Once per study: 1 hour.
Actions: daily completion of diary (sleep, diet and physical activity),
completion of 4 questionnaires concerning sleep habits. Collection of saliva
following study day (3 times per studyday), by chewing on cotton collector.
Risks: none.
Albinusdreef 2
Leiden 2333 ZA
NL
Albinusdreef 2
Leiden 2333 ZA
NL
Listed location countries
Age
Inclusion criteria
- Informed consent
- Caucasian men
- Age between 18 and 55 years
- BMI between 20 and 25 kg/m2 (equally divided over the range, so ideally n=12 in BMI categories 20 -25; 25 - 30; 30 - 35 kg/m2)
Exclusion criteria
Active endocrine disease (e.g. diabetes mellitus type 1 and type 2, thyroid disease, Cushing*s disease and lipid-associated disorders such as FH)
- Fasting glucose >7.0 mmol/L
- Severe chronic disease (e.g. chronic liver or kidney disease)
- Severe insomnia, sleep disorders or exceptional habitual sleep duration (<6 or >10 h).
- Medication use including the following: lipid lowering drugs, glucocorticoids, sleep medication, hormone replacement, glucose lowering drugs, insulin therapy (last 6 weeks), anticoagulants
- Recent time zone travel (last 6 weeks)
- Shift work (last 6 weeks)
- Severe alcohol use (>21 units/week)
- Psychiatric disease
- Drug abuse
- Recent participation to another nutritional or biomedical trial (last 6 weeks)
- Taking medication, which may interfere with study measurements, as judged by the responsible physician
- Reported weight loss or weight gain (10%) in the last six months prior to the pre-study screening
- Clinically relevant abnormalities in clinical chemistry at screening (to be judged by the study physician)
- Reported use of any nicotine containing products in the six months preceding the study and during the study itself;
- Extreme strenuous exercise during last 3 months, as judged by responsible physician
- Excessive sunbathing during the last 3 months, as judged by responsible physician
Design
Recruitment
metc-ldd@lumc.nl
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In other registers
| Register | ID |
|---|---|
| CCMO | NL55111.058.15 |