Research Review By Christopher Howard©

Date Posted:

November 2010

Study Title:

Prolonged Sleep Restriction Affects Glucose Metabolism in Healthy Young Men

Authors:

van Leeuwen WMA, Hublin C, Sallinen M et al.

Author's Affiliations:

Brain and Work Research Centre, Finnish Institute of Occupational Health, Helsinki, Finland; Department of Physiology, Institute of Biomedicine, University of Helsinki.

Publication Information:

International Journal of Endocrinology 2010; 1-7.

Background Information:

Sleep is a restorative process that is necessary for all of the organ systems of the human body, including the digestive, cardiovascular, and immune systems. However, in today’s fast paced society, voluntary restriction of sleep is becoming more and more common, due primarily to increased work demands and atypical work hours.

The consequences of such sleep restriction are many and include an increased susceptibility to accidents (traffic and otherwise), increased prevalence of certain diseases, and even increased mortality. It is, therefore, important to further research the relationship between sleep and health to help an increasingly sleep deprived population.

Proper sleep is a key factor in the regulation of energy metabolism. Several studies have indicated that sleep deprivation is correlated with increased risk of developing obesity and diabetes (1,2). Glucose tolerance has been shown to be impaired following restriction of sleep to four hours per night for six consecutive days (3).

In addition, it has been shown that two nights of sleep restriction to four hours results in a reduction of the satiety hormone leptin and an accompanying increase in hunger and the orexigenic factor ghrelin (4).

It is the goal of this study to examine the effects of accumulating sleep restriction during five working days followed by two recovery days on changes in several metabolic parameters, such as glucose metabolism, serum leptin concentrations, and feelings of satiety.

Pertinent Results:

Total Sleep Duration and Cortisol Profile:
  • The average total sleep duration in the control group remained unaffected, whereas average total sleep duration decreased in the experimental group, as expected.
  • The cortisol profile was unaffected throughout the experiment in the control group. In the experimental group, peak cortisol levels were delayed 16.2 +/- 5.5 min after sleep restriction compared to baseline.
Glucose, Insulin, and IGF-1:
  • Glucose levels remained at baseline in the control group. Glucose levels in the experimental group showed a trend toward reduced levels after sleep restriction and showed a significant decrease after recovery to 65.5 +/- 1.3% of baseline values.
  • In the control group, insulin levels remained at baseline throughout the experiment. In the experimental group, insulin levels were elevated after sleep restriction to 159.9 +/- 25.6% of baseline levels and returned back to baseline after recovery.
  • In the control group, insulin-to-glucose ratio remained at baseline throughout the experiment. In the experimental group, insulin-to-glucose ratio was significantly elevated after sleep restriction (160.0 +/- 25.4% of baseline) and returned back to baseline levels after recovery.
  • In the control group, IGF-1 levels remained at baseline throughout the experiment. In the experimental group, IGF-1 levels showed a tendency for an increase after sleep restriction and were significantly elevated after recovery(P < .01).
Leptin and Subjective Satiety:
  • Leptin levels were increased in the experimental group after sleep restriction (P < .01) and still significantly elevated after recovery (P < .01). Leptin levels remained at baseline level in the control group.
  • Feelings of satiety were unaffected in both groups and remained at baseline level.

Clinical Application & Conclusions:

It has been previously shown that several common disorders are epidemiologically linked with habitual sleep deprivation including cardiovascular diseases, type 2 diabetes, and obesity. In this study, it was shown that glucose levels declined, while insulin levels increased in response to sleep deprivation.

Thus the insulin-to-glucose ratio was also elevated, indicating a reduced sensitivity to insulin. Reduced insulin sensitivity can increase the risk of type 2 diabetes. In addition, decreased glucose levels as a result of sleep deprivation are worrisome because glucose is the primary energy supply for the brain.

On the positive side, it was shown that two nights of recovery sleep restored baseline values of the variables measured, indicating that the body can recover from sleep deprivation. In addition, this study showed that sleep deprivation did not increase feelings of hunger, possibly due to the elevated levels of leptin.

This could indicate that sleep restriction may not increase the risk of obesity as previously thought. Further research is required to clarify this particular relationship.

Study Methods:

Subjects:
  • Twenty-three healthy men aged 19-29 participated in this study.
  • Volunteers were screened during a telephone interview, followed by a thorough physical examination, blood tests, and screening polysomnography.
  • Volunteers were excluded from participation for any of the following: an irregular sleep-wake schedule, regular naps, having either advanced or delayed sleep phase syndrome, insomnia or other sleep problems, loud snoring >5 nights/week, repeating apneas, excessive daytime sleepiness (Epworth Sleepiness Scale >8), restless legs at least once a month, a disorder that might become worse because of prolonged wakefulness (such as a severe mental disorder, epilepsy, and cardiac arrhythmia), excessive caffeine consumption (>5 cups of coffee/day), excessive alcohol consumption (>15 units/week; 1 unit = 11 g or 13.9mL of alcohol), smoking, medication affecting the central nervous system during the last two weeks, any clinically relevant abnormality on blood tests, any other reason that health may be harmed because of if participating, apnea-hypopnea index >20, periodic limb movement index >25, epileptiform activity on the EEG, abnormal urinary drug screening, and having experienced a significant recent life event that could disturb sleep.
  • Volunteers had to meet the following criteria to be included in the study: male aged 19–29, sleep latency in the evening < 20–30 minutes, uninterrupted nocturnal sleep and if awakened no problem to fall asleep again, no chronic disease or symptom affecting sleep, no continuous medication, and willing and able to participate.
  • For at least one week prior to the experiment participants completed sleep diaries and carried actigraphs in order to verify adherence to a regular sleep-wake schedule. One week prior to the start of the experiment, participants had an adaptation night in the sleep laboratory.
Experimental Design:
  • A 10-day experimental schedule was executed at the Brain and Work Research Centre of the Finnish Institute of Occupational Health (FIOH).
  • Fifteen participants were randomly allocated to the experimental group (EXP). This group spent the first two nights in bed 8 hours (from 23:00 h to 07:00 h), followed by five nights of 4 h in bed (from 03:00 h to 07:00 h) and, three nights of 8 hours in bed for recovery.
  • Eight participants were randomly allocated to the control group (CON) and spent 8 h in bed every night.
  • Sleep was not allowed during the daytime, which was monitored using EEG and a continuously present investigator. During the hours in which the participants were awake, they participated in a larger experiment at the sleep laboratory which investigated a simulated work week.
  • Saliva samples were taken ten times per day and blood pressure was measured eight times per day. In addition, polygraphy and ECG were measured continuously.
  • Participants ate standardized meals at fixed times throughout the experiment: breakfast at 08:00am (600 kcal), lunch at 12:30pm (800 kcal), snack at 3:30pm (300 kcal), dinner at 6:30pm (700 kcal) and snack at 9:30 pm (200 kcal). In addition, participants in EXP ate a piece of fruit (apple or orange) at 00:30 h (50 kcal).
Hormonal Measurements:
  • Hormone levels were assessed from blood samples taken at the following times: before breakfast at 7:30 am after the second baseline night, after the fifth night of sleep restriction, and after the second recovery night in the experimental group. Corresponding samples were taken in the control group.
  • Samples were analyzed for glucose, insulin, IGF-1, and leptin. In addition, prior to bloodwork, subjects were asked to rate how hungry they were on a scale of 1-5 (1 = very hungry, 5= very satiated). Saliva samples were used to determine cortisol levels.
Statistical Analysis:
  • Sleep restriction values and recovery values were compared to baseline values by applying paired t-tests for normally distributed differences and Wilcoxon signed ranks tests for differences that were not normally distributed. The normality of differences was checked using Kolmogorov-Smirnov goodness of fit test. A P-value <.05 was considered to be statistically significant.

Study Strengths / Weaknesses:

One shortcoming of this study is that it used two different groups of people for the control and experimental groups. Perhaps a study in which two groups undergo both an experimental and control protocol would be better in this situation as sleep and sleep restriction affects everyone differently.

In addition, the authors made no mention of the fact that the experimental group had twice the leptin levels of the control group at baseline. Although the control group remained consistent at all time points, it does make one wonder why the two groups had such drastically different levels.

The addition of a recovery period in the study design was important, as it allowed the researchers to see what would happen if the body was allowed sufficient sleep after a period of deprivation. It has been common perception that the body doesn’t “make up for lost sleep,” but according to the results of this study, it does to some extent.

Additional References:

  1. S. R. Patel and F. B. Hu, “Short sleep duration and weight gain: a systematic review,” Obesity 2008; 16(3): 643–653.
  2. B. Schultes, S. Schmid, A. Peters, J. Born, and H. L. Fehm, “Sleep loss and the development of diabetes: a review of current evidence,” Experimental and Clinical Endocrinology and Diabetes 2005; 113(10): 563–567.
  3. K. Spiegel, R. Leproult, and E. Van Cauter, “Impact of sleep debt on metabolic and endocrine function,” Lancet 1999; 354: 1435–1439.
  4. K. Spiegel, E. Tasali, P. Penev, and E. Van Cauter, “Brief communication: sleep curtailment in healthy young men is associated with decreased leptin levels, elevated ghrelin levels, and increased hunger and appetite,” Annals of Internal Medicine 2004; 141(11): 846–850.