We found that habitual sleep duration below 7.7 h was associated with increased BMI, similar to findings in other studies including children [1
], adolescents [5
], and adults [2
]. We also report a significant association of sleep duration with leptin and ghrelin that is independent of BMI, age, sex, SDB, and other possible confounding factors (analysis not shown for SDB and other confounders). Short sleep duration was associated with decreased leptin and increased ghrelin, changes that have also been observed in reaction to food restriction and weight loss and are typically associated with increased appetite. These hormone alterations may contribute to the BMI increase that occurs with sleep curtailment.
Previous studies have shown that both acute sleep deprivation [18
] and chronic partial sleep deprivation (sleep restriction) [19
] can cause a decrease in serum leptin concentrations. These studies, however, were performed under highly controlled laboratory circumstances. Our results validate the association of decreased leptin with decreased sleep time in a large sample of adults under real-life conditions and, now, indicate a role for ghrelin. Leptin deficiency increases appetite and produces obesity [8
]. Leptin administration suppresses food intake and reduces energy expenditure [21
]. Importantly, low leptin as observed with sleep loss has a greater impact on appetite than high leptin levels, which are associated with leptin resistance, as occurs with obesity [8
Levels of ghrelin, a potent stimulator of appetite [23
], were higher in those with shorter sleep. Ghrelin levels are also positively associated with hunger ratings [26
], but decrease with increased BMI (see ). In one study, after 3 mo of dietary supervision, a reduction in BMI of approximately 5% was associated with a 12% increase in ghrelin and a 15% decrease in leptin [27
]. These changes, in participants of similar BMI to our sample and presumably producing increased appetite, are comparable to those observed with sleep loss of 2–3 h/night. With sleep loss, however, relatively high ghrelin and low leptin levels are associated with increased BMI. These changes can be hypothesized to play a contributory, rather than compensatory, role in the development of overweight and obesity with sleep restriction.
Our findings are strengthened by the large and well-characterized population-based sample, attention to bias and confounding factors, and in-laboratory polysomnographic data. The changes in hormones with sleep duration were consistent and of significant magnitude. They also represent the first demonstration of a correlation between peripheral hormone levels and both self-reported (questionnaire and diary data) and polysomnographically determined sleep amounts in a general population sample. While these data are more comprehensive than previous studies on this topic, some misclassification error may exist because of intra-person variability or limitations of polysomnographic measurement. Little is known about the stability of self-reported sleep duration and polysomnographic measures of sleep duration over time. We examined the stability of the self-reported sleep duration data, and found these measures to be stable. For 860 participants who completed three surveys, the mean (standard deviation) of intra-person differences in usual sleep for two 5-y periods was 0.10 (0.47) h. For 190 participants with at least three sleep diaries, the mean (standard deviation) of intra-person differences in average nightly sleep for two 4-y intervals was 0.09 (0.41) h. Furthermore, the subjectively reported hours of usual sleep and the diary-derived average nightly sleep values were highly correlated (r = 0.55, p < 0.001). One-night polysomnographically defined total sleep time had a similar intra-person mean difference (0.10 h), with a somewhat larger standard deviation (0.68) for 713 participants with at least three sleep studies.
Elevated ghrelin mainly correlated with acute sleep loss as measured by polysomnography immediately prior to blood sampling (see ; B), while reduced leptin correlated with chronic sleep restriction indicated by self-reported sleep measures (see ; A). Measures of usual and one-night polysomnographically defined sleep time were only weakly, but statistically significantly, correlated (r = 0.12, p < 0.001), supporting the concept that these measures reflect long-term and short-term changes in sleep amounts, respectively. Our findings are in agreement with the current view that leptin is important in signaling long-term nutritional status while ghrelin has a more significant role in acute hunger. The changes in leptin and ghrelin with sleep restriction could, therefore, provide a powerful dual stimulus to food intake that may culminate in obesity.
Longitudinal and intervention studies will be necessary to define further the link between sleep curtailment and increased BMI. Only total ghrelin was measured, since active octanoylated ghrelin is unstable. Although both total and active ghrelin appear to be regulated in a similar and parallel manner, future studies will need to focus on measurement of the biologically active form. Other potentially important appetite regulatory hormones, such as PYY 3–36 [28
], were not measured. Measures of appetite were not included in the Wisconsin Sleep Cohort Study overnight protocol; therefore, a direct examination of the relationship between the observed hormone changes with sleep duration and alterations in appetite was not possible.
Hormone measurements were all performed on a single fasted, morning sample and may not reflect the 24-h profile. It is possible that participants with shorter sleep woke up earlier and that hormone differences may be partially related to circadian time. Leptin and ghrelin levels rise slightly during the night [29
], and this could result in higher hormone levels in short sleepers. This may be an issue for ghrelin, as levels increased with acute sleep restriction. It is, however, unlikely to play a role in the leptin finding, since lower levels were found with chronic but not acute sleep restriction. Additionally, studies have shown a high correlation between morning, fasting leptin and ghrelin levels and 24-h mean profile [29
]. We also found that the ghrelin and leptin changes were unaffected by morningness tendencies. The fact that studies investigating the diurnal profile of these hormones found similar hormonal changes over the entire 24-h period after experimental sleep restriction also corroborates our results [18
]. The robustness of our findings and similar observations from smaller controlled studies [18
] also suggest that our statistically significant results are unlikely to be a reflection of the number of analyses carried out.
Animal studies have suggested a link between sleep and metabolism [31
]. In rats, prolonged, complete sleep deprivation increased both food intake and energy expenditure. The net effect was weight loss and, ultimately, death [33
]. Rats fed a high protein-to-calorie diet had accelerated weight loss, compared to sleep-deprived rats fed calorie-augmented (fatty) diets [32
]. Food consumption remained normal in sleep-deprived rats fed protein-rich diets, but increased 250% in rats fed calorie-rich diets. Preference for fatty foods has also been reported anecdotally in sleep-deprived humans [32
]. Sleep deprivation may thus increase not only appetite but also preference for lipid-rich, high-calorie foods. Animal experiments that have found weight loss after prolonged sleep deprivation have to be interpreted in the context of a stressful procedure producing intense sleep debt [35
], which may interfere with adequate food intake. From our study, we hypothesize that the moderate chronic sleep debt associated with habitual short sleep is associated with increased appetite and energy expenditure. In societies where high-calorie food is freely available and consumption uncontrolled, after milder chronic sleep restriction, the equation may be tipped towards food intake for high-calorie food rather than expenditure, culminating in obesity. Short sleepers may also have more time to overeat.
Sleep loss from a baseline of 7.7 h was associated with a dose-dependent increase in BMI. This was the predominant effect in a population increasingly curtailing sleep [37
]. Sleep greater than 7.7 h, however, was also associated with increased BMI. Patients with SDB (a pathology associated with increased BMI) may spend a longer time in bed to compensate for fragmented sleep; however, controlling for AHI did not change the curvilinear BMI–sleep association. Another possibility is that in long sleepers, reduced energy expenditure due to increased time in bed has a greater impact than reduced food intake. In favor of this hypothesis, long sleepers exercise less [38
]. In our data, we found that the odds ratio of high levels of self-reported exercise (>7 h/wk), based on a single survey question, decreased with increased sleep time, but controlling for this variable also did not change our findings (analyses not shown).
Insulin resistance with sleep deprivation has been reported in a laboratory study of young, healthy volunteers [39
]. When controlling for BMI, we found no significant correlation between insulin, glucose, or adiponectin levels and various measures of sleep duration. Also, there was no significant correlation between QUICKI (or the homeostatic model assessment HOMA [16
]; data not shown) and sleep duration. This may be due to difficulties in detecting small effects on glucose tolerance under less-controlled conditions of large population studies.
Our results demonstrate an important relationship between sleep and metabolic hormones. The direct effect of chronic partial sleep loss on food intake, energy expenditure, and obesity now needs to be explored. Altering sleep duration may prove to be an important adjunct to preventing and treating obesity.
Why Was This Study Done?
Recent studies have shown that there is a link between sleeping less and gaining weight. It isn't clear why there is this link—perhaps, for example, those who are awake in the middle of the night tend to head for the refrigerator for a snack. Another possibility is that the amount of sleep that we have might affect the hormones that control our appetite. We know that extreme sleep deprivation affects the level of leptin, a hormone that controls appetite. Here, the researchers wanted to study levels of leptin and other appetite hormones under more normal conditions, in people with a range of sleeping habits.
What Did the Researchers Do?
The researchers studied participants in a large sleep study that has been going on in Wisconsin for over 15 years. These participants have been filling out questionnaires about their sleep habits and their health in general, have kept sleep diaries, and have occasionally spent a night in the laboratory, where researchers studied their sleep in more detail. After sleeping overnight in the laboratory, the participants gave blood samples, which were tested for hormones.
What Did They Find?
The researchers found that people who slept less were on average heavier. And people who slept less had lower levels of leptin and higher levels of ghrelin, another hormone that controls food intake.
What Does This Mean?
The combination of low leptin and high ghrelin is likely to increase appetite. In other words, short sleep might stimulate appetite, which increases weight.
Future studies need to examine the effect of regular short sleeping hours on appetite, food intake, and obesity. These studies could help to answer the question of whether the rise in obesity in many societies is partly due to the fact that people are sleeping less. And it seems well worth testing whether increasing sleep to seven or eight hours per night could help people to lose weight.
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