Journal of Obesity & Metabolic Syndrome 2018;27:4-24

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Sleep and Obesity

Chenzhao Ding1, Lee Ling Lim1,2, Li Xu1, Alice Pik Shan Kong1,*
Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China; 2Department of Medicine, Faculty of
1

Medicine, University of Malaya, Kuala Lumpur, Malaysia

Rising global prevalence and incidence of obesity lead to increased cardiovascular-renal complications and can-
Received February 28, 2018
cers. Epidemiological studies reported a worldwide trend towards suboptimal sleep duration and poor sleep Reviewed March 8, 2018
quality in parallel with this obesity epidemic. From rodents and human models, it is highly plausible that abnor- Accepted March 9, 2018
malities in sleep, both quantity and quality, impact negatively on energy metabolism. While excess dietary in-
*Corresponding author
take and physical inactivity are the known drivers of the obesity epidemic, promotion of healthy sleep habits has
Alice Pik Shan Kong
emerged as a new target to combat obesity. In this light, present review focuses on the existing literature exam-
ining the relationship between sleep physiology and energy homeostasis. Notably, sleep dysregulation perturbs
the metabolic milieu via alterations in hormones such as leptin and ghrelin, eating behavior, neuroendocrine https://orcid.org/0000-0001-8927-6764
and autonomic nervous systems. In addition, shift work and trans-meridian air travel may exert a negative influ- Department of Medicine and
ence on the hypothalamic-pituitary-adrenal axis and trigger circadian misalignment, leading to impaired glu- Therapeutics, Prince of Wales Hospital,
cose tolerance and increased fat accumulation. Amassing evidence has also suggested that uncoupling of the The Chinese University of Hong Kong,
Shatin, NT, Hong Kong SAR, China
circadian clock can increase the risk of adverse metabolic health. Given the importance of sleep in maintaining Tel: +852-3505-1558
energy homeostasis and that it is potentially modifiable, promoting good sleep hygiene may create new ave- Fax: +852-2637-3852
nues for obesity prevention and treatment. E-mail: [email protected]

The first two authors contributed equally

Key words: Sleep, Energy metabolism, Leptin, Ghrelin, Pituitary-adrenal system, Circadian rhythm to this study.

INTRODUCTION short sleep duration as < 8–10 hours and < 7 hours per day in ado-
lescents and adults aged 18–60 years respectively, considering the
The global prevalence of obesity has doubled since 1980, affect- potential risks in association with the development of cardiometa-
ing 107.7 million children and 603.7 million adults in 2015, with bolic disease and death.4-6 Due to increasing demand from school,
more than two-thirds of the United States population being either work and leisure activities2, along with the prevalent usage of Inter-
overweight or obese.1 This rapid surge in obesity is driven mainly net and electronic devices, there is a global phenomenon for a shift
by lifestyle factors such as physical inactivity, unhealthy dietary in both adolescents and adults to have shorter sleep duration com-
choices and patterns. Emerging evidence suggests that sleep dis-
2
pared to a few decades ago. Based on the 2014 U.S. Behavioral Risk
turbances (e.g., suboptimal sleep duration, poor sleep quality, circa- Factor Surveillance System, more than one-third of adults were
dian misalignment and insomnia), may contribute to obesity and short sleepers, particularly prevalent in those who were young,
type 2 diabetes mellitus (T2DM). Physiologically, sleep duration
2
obese (body mass index [BMI] ≥ 30 kg/m2) or with low socioeco-
declines during transition from infancy, puberty to late adulthood.3 nomic and education status.7 In China, a meta-analysis of 17 cross-
Optimal sleep duration has been a matter of controversy but recent sectional population-based studies reported that every one in six
consensus of the American Academy of Sleep Medicine defines adults had insomnia, which was again more commonly seen in

Copyright © 2018 Korean Society for the Study of Obesity

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Ding C, et al. Sleep and Obesity

young individuals.8 Paradoxically, long sleep duration ( > 9 hours drate-rich night-time snacks.20 These were accompanied by a lack
per day) was also observed in 23%–37% of the general population of compensatory increase or even with a reduction in 24-hour en-
in developed countries , and a meta-analysis of 137 prospective co-
9
ergy expenditure, leading to positive energy balance.19,20 In keeping
hort studies reported a dose-response relationship with incident with these findings, an inverse relationship between sleep duration
cardiovascular disease and death, attesting a U-shaped relationship and total energy and macronutrient intake was evident in epidemi-
between sleep duration and health outcomes across all age groups.10,11 ological cohorts.15,17,21,22 In a meta-analysis of 14,906 Europeans
Alarmingly, poor sleep quality (defined as global Pittsburgh Sleep from the Cohorts for the Heart and Aging Research in Genomic
Quality Index score > 5) was also independently associated with Epidemiology Consortium, younger people (aged 20–64 years)
an increase in BMI and worse glycemic control.6 Given that obesity with short sleep duration were independently associated with high-
is closely linked to multiple chronic diseases, notably diabetes and er relative saturated fatty acids intake, whereas older women (aged
cancer which are the leading causes of morbidities and mortality in 65–80 years) with similar exposure demonstrated higher relative
many parts of the world , the perplexing relationship between
12
carbohydrate, lower relative total fat and polyunsaturated fatty acids
sleep and energy metabolism call for more research and clinical at- consumption.22 In the 2005–2010 U.S. National Health and Nutri-
tention, as sleep is an essential part of life and a potentially modifi- tion Examination Survey involving 15,199 community-dwelling
able behavioral risk factor for metabolic health. Here, we review adults, short sleepers reported frequent snacking and increased to-
some of the important findings in this field, and discuss the mecha- tal glucose intake.17 Similarly, amongst 2,828 Chinese adults, those
nisms linking sleep, energy metabolism and obesity. with less than 7-hour sleep had excess fat intake than the group
with 7- to 9-hour sleep.21
SLEEP AND NEUROHORMONAL Accumulating evidence suggests that sleep disruption may inter-
DYSREGULATION fere with the feeding and satiety signals at the hypothalamic feeding
circuits.23 A shift towards increased hunger in short sleepers was
Sleep and satiety driven by decreased leptin level with or without a concomitant
The appetite center, located at the ventromedial and arcuate nu- change in the diurnal rhythm amplitude of leptin, increased ghrelin
clei of the hypothalamus, is regulated by hormones including leptin level or both.24,25 In healthy young adults with stable caloric intake
and ghrelin. Leptin is an adipocyte-derived hormone which sup- and activity levels, 6 days of sleep restriction (4 hours in bed per
presses appetite, whilst ghrelin is mainly a stomach-derived hunger- night) was independently associated with a 26% reduction in leptin
promoting peptide. 13,14
High total energy and fat intake, night-time than sleep extension (12 hours in bed per night), on top of a flat-
snacking and binge eating tendencies have been reported to be as- tened diurnal profile of leptin secretion.25 In the prospective Wis-
sociated with sleep curtailment.15,16 The potential mechanisms me- consin Sleep Cohort Study involving 1,024 healthy adults, com-
diating the effects of sleep debt on obesity are complex, which in- pared with those with 8-hour of sleep, short sleepers (5-hour of
clude alterations in eating behavior (e.g., skipping meals, snacking, sleep per day) had a 16% decrease in leptin and 15% increase in
and irregular meal times), increased ghrelin to leptin ratio and acti- ghrelin level.24 Interestingly, diminished activity of the appetitive
vation of hedonic pathways.15,17,18 Several small scale experimental desire and food stimulus evaluation regions within the frontal, in-
studies involving the healthy population (number of subjects, 11 to sular and cingulate cortices, along with enhanced activity of amyg-
26 in each study) examined the effect of sleep restriction on dietary dala are other plausible pathways linking sleep curtailment to obe-
intake and patterns under the controlled environment, which in- sity.26-28 The disrupted neural circuits led to hedonic hunger and
cluded objective sleep measurements and planned meals in both preferences for highly palatable and rewarding energy-dense food26-28,
phases of short and habitual sleep.19,20 Sleep restriction was report- albeit with inter-individual variation in the magnitude of change in
ed to be associated with an increase in total energy, total fat and sat- eating behavior proportional to the severity of sleep curtailment.26
urated fatty acids intake19, as well as high consumption of carbohy- On the other hand, short sleepers have prolonged wakefulness that

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Ding C, et al. Sleep and Obesity

promotes obesogenic eating behavior e.g., meal-skipping, frequent to the usual circadian rhythm as seen during the sleep extension
snacking and increase intake of low-quality diet. 17,29,30
Late-time eat- period (12 hours in bed per night for a week).32 This prolonged ex-
ing, which was defined as caloric intake after 8:00 PM, also signifi- posure to elevated GH level may interact with the hunger-promot-
cantly predicted an increase in BMI, suggesting that eating late at ing ghrelin centrally or stimulate peripheral glucose and lipid catab-
night may lead to obesity. Moreover, decreased nocturnal ghrelin
29
olism, resulting in insulin resistance and positive energy balance.37
levels were found in men with insomnia compared with their age- These findings were supported by some but not all observational
and body weight-matched healthy control (n = 25), while no differ- studies, which reported a U-shaped relationship between IGF-1 to
ence of leptin levels was found between groups.31 IGFBP-3 ratio, anthropometric traits (e.g., BMI and waist circum-
ference) or risk of metabolic syndrome.38,39 To this end, a better un-
Sleep and growth hormone-insulin like growth factor-1 derstanding of the cellular-microenvironment interactions and
axis their downstream signaling cascades integrating sleep, GH/IGF-1
The growth hormone (GH)-insulin like growth factor-1 (IGF-1) axis and metabolic functions is warranted.
axis also plays a role in the regulation of adiposity and glucose ho-
meostasis. Under a normal sleep/wake cycle, there is a spontane- Sleep and hypothalamic-pituitary-adrenal axis
ous nocturnal GH pulse during the restorative slow wave sleep Sleep disturbances, including short sleep, sleep debt, and circadi-
(SWS) that occurs within the first 3 hours of sleep, with both dem- an misalignment, may also disrupt glucose homeostasis and cause
onstrating a dose-dependent relationship. Increasing evidence
32
metabolic perturbations via other hormonal and cellular signaling
suggests that there are biological interactions of GH/IGF-1 axis cascades.23,24,40 In a pilot study conducted in 11 healthy young men,
with sleep dysregulation. Sleep curtailment and late chronotype are decreased glucose tolerance, increased evening cortisol level and
associated with suppressed GH and IGF-1 pulsatility, followed by a sympathetic over-activity were observed after sleep restriction (4
compensatory increase in IGF-binding protein 3 (IGFBP-3) level hours in bed per night for six consecutive nights) compared with
via the negative feedback loop. In a 4-year prospective cohort
33
the measurements taken after a sleep-restorative period (12 hours
study of normoglycemic adults, low circulating IGF-1 level had a in bed per night for seven consecutive nights), indicating that sleep
50% excess risk of developing either impaired glucose tolerance or debt had a detrimental effect on glucose metabolism and endo-
T2DM, consequent to decreased peripheral insulin sensitivity and crine function.40
hyperinsulinemia.34 In the Danish-Monitoring Trends in Cardio- The bidirectional relationships between sleep and the activity of
vascular Diseases study, after a mean follow-up of 15 years, either a hypothalamic-pituitary-adrenal (HPA) axis may exert negative
low IGF-1 or high IGFBP-3 level was independently associated metabolic consequences. Dysregulation of the HPA axis and its cir-
with a relative risk (RR) of 1.94–2.22 of incident coronary heart cadian rhythm can mediate the impact of sleep disturbances on
disease, after adjustment for other cardiovascular risk factors. Sev-
35
cardiometabolic risk, mainly via the actions of two counter-regula-
eral mechanisms were postulated to explain the pleiotropic effects tory hormones, namely the glucocorticoids and catecholamines.
of GH/IGF-1 axis on the retardation of atherosclerosis e.g., re- Physiologically, cortisol level peaks after 30–45 minutes of awaken-
duced systemic and vascular oxidative stress (low interleukin-6 and ing (defined as cortisol awakening response [CAR]), followed by a
tumor necrosis factor-alpha levels), decreased aortic stiffness and sharp decline over the next 3 hours, more gradual decline over the
control of de novo hepatic lipid metabolism. 35,36
rest of the day, and reaching nadir during the first half of sleep cy-
In contrast to the aforementioned findings, another experimental cle.41 Existing studies examining the associations between sleep and
sleep restriction (4 hours in bed per night for six consecutive circadian variability of cortisol secretion is inconclusive, due to dif-
nights) study involving 11 healthy young men revealed a biphasic ferences in the sleep measurements (actigraphy/polysomnography
pattern of nocturnal GH release, with the first pulse occurred at vs. self-reported sleep parameters), definitions used for sleep dura-
3-hour prior to the sleep onset and the second peak corresponded tion and quality, and the number of real-time sampling points for

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Ding C, et al. Sleep and Obesity

modelling of 24-hour cortisol profile. Several reports indicated that

Genetic &
short sleepers have flattened diurnal cortisol slope and raised eve-  Sleep
environmental
factors
ning cortisol followed by an aggravated CAR, yielding an increase  LDL-cholesterol
 Apolipoprotein B
in total daily cortisol secretion which ends up in a state of hyper-
cortisolism and catabolism.42-44 In school-age children, high CAR  Ghrelin  Cortisol  Sympathetic activity

and subsequent diurnal cortisol level were inversely associated with

short sleep duration, low sleep efficiency and low frequency of  Leptin
Obesity
SWS.45,46 Conversely, two other studies found no association be-
tween objective sleep duration and salivary awakening cortisol44 or
24-hour urinary cortisol level.47 Poor sleep quality has been report-  Sleep apnea Cardiovascular diseases
ed to be an independent stressor for excess cortisol and catechol-
Figure 1. Association between sleep, obesity, cardiovascular risks and possible
amines secretion, particularly with greater magnitude in adoles- underlying neurohormonal dysregulation. LDL, low-density lipoprotein.
cents at late puberty.42,44 Increased HPA axis activation has also
been reported in subjects with insomnia.48,49 Furthermore, it has SLEEP, OBESITY AND DIABETES
been suggested that a gender difference on this stress reaction relat-
ed to sleep disturbances which may be modulated by the type of Multiple studies have consistently demonstrated significant asso-
sleep disorders involved, calling for more studies to investigate the ciations between sleep curtailment with decreased resting and
impact of sex hormones on sleep and energy balance. 44,50
postprandial energy expenditure (~5% and 20%, respectively), in-
Sympathetic over-activity may also contribute to the neurohor- creased appetite and insulin resistance in general population.2,11 In
monal dysregulation linking sleep curtailment to energy imbalance. addition, a randomized cross-over study demonstrated a 30% de-
In addition to a 1.5-hour delay in the nocturnal nadir of cortisol crease in the intracellular insulin sensitivity within adipocytes from
level, experimental sleep restriction with 4 hours in bed per night the subcutaneous fat samples of seven healthy adults collected after
for six consecutive nights in healthy volunteers had shown a con- sleep restriction compared with after normal sleep.53 It has also
comitant 24-hour lowering of heart rate variability (measured by been demonstrated that short sleep duration is associated with ath-
the autocorrelation coefficient of consecutive interbeat intervals) erogenic dyslipidemia.54,55 Once obesity sets in, there may be a vi-
especially during awakening, which reflected an increase in cardiac cious cycle as obesity associated comorbidities such as obstructive
sympathetic activity and/or diminished vagal tone, compared with sleep apnea may further compromise sleep quality in affected indi-
sleep extension phase (12 hours in bed per night for seven consec- viduals (Fig. 1). Taken together, evidence to date suggests that
utive nights). Physiologically, sleep onset is associated with de-
25
sleep curtailment affects the resiliency of neurohormonal stress re-
creased catecholamines release, reaching a nocturnal nadir an hour sponse and predisposes to metabolic disturbances with possible
into a restful sleep. Amongst short sleepers, the secretion of nor-
51
long-term cardiovascular risk. Besides sleep curtailment, there have
epinephrine was pathologically elevated during early awakening in been a wealth of clinical evidence supporting the association of
early morning, between 3:00 AM and 6:00 AM, with epinephrine sleep disturbances, both quantity and quality, with obesity and dia-
showing a similar trend. 44,51
Furthermore, patients with mild to betes (Tables 1 and 2).11,56-103 However, the associations of insom-
moderate hypertension with acute sleep restriction reported an nia with obesity and glucose metabolism is under debate.
early morning elevation in blood pressure (systolic blood pressure Insomnia is a common sleep problem worldwide and affects
of 7 mmHg and diastolic blood pressure of 4 mmHg) and heart 15% of the Chinese population.8 It is defined as difficulty in initiat-
rate (5.5 beats per minute) with potential risk of silent cardiovascu- ing sleep (DIS), difficulty in maintaining sleep (DMS) and/or early
lar event, as sequelae of their blunted nocturnal dipping related to a morning awakening (EMA) at least three times per week with as-
surge in norepinephrine release. 52
sociated impairment of daytime functioning.104 Nonrestorative

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 Table 1. Clinical studies examining the association between sleep duration with obesity and diabetes
Type of study/ Study population Definition of sleep Method of sleep Age (yr) and
Author (year) Outcome
country or region (sample size) disturbances assessment male (%)
Sleep duration and overweight/obesity
Ayas et al. (2003)11 Prospective (mean Female married registered nurses Short sleep: ≤ 5 hr/day Self-reported 40–65, 0% New-onset obesity
follow-up: 10 yr)/ from the Nurses’ Health Study Long sleep: ≥ 9 hr/day sleep duration Short sleep: RR, 1.18; 95% CI, 0.96–1.44
the United States (n= 70,026) Reference: 8 hr/day Long sleep: RR, 1.29; 95% CI, 1.05–1.59
Patel et al. (2006)56 Prospective study Female nurses from the Nurses’ Sleep duration was Self-reported 39–65, 0% New-onset obesity
Ding C, et al. Sleep and Obesity

(follow-up: 16 yr)/ Health Study (n= 68,183) categorized as: Sleep duration ≤ 5 hr/day: HR, 1.15; 95% CI, 1.04–1.27

8 | http://www.jomes.org
the United States ≤ 5, 6, 7, 8, and ≥ 9 hr/ Sleep duration 6 hr/day: HR, 1.06; 95% CI, 1.01–1.12
day Sleep duration ≥ 9 hr/day: HR, 1.03; 95% CI, 0.93–1.14
Reference: 7 hr/day ≥ 15 kg weight gain
Sleep duration ≤ 5 hr/day: HR, 1.28; 95% CI, 1.15–1.42
Sleep duration 6 hr/day: HR, 1.10; 95% CI, 1.04–1.17
Sleep duration ≥ 9 hr/day: HR, 1.04; 95% CI, 0.92–1.16
Chaput et al. (2008)57 Prospective study General population form the Quebec Short sleep: 5–6 hr/day Self-reported 21–64, 42.4% Weight gain
(follow-up: 6± 0.9 Family Study Long sleep: 9–10 hr/day Short-duration sleepers gained 1.84 kg; 95% CI, 1.08–2.61
yr)/Canada (n= 276; nonobese: n= 224) Reference: 7–8 hr/day Long-duration sleepers gained 1.49 kg; 95% CI, 0.92–2.48
New-onset obesity
Short-duration sleepers: OR, 1.27; 95% CI, NS
Long-duration sleepers: OR, 1.21; 95% CI, NS
López-García et al. Prospective study Elderly population (n= 3,235) Sleep duration was cate- Interview Male, 71.6± 8.0; ORs of obesity
(2008)58 (follow-up: 2 yr)/ gorized as: ≤ 5, 6, 7, 8, 9, female, 72.1± 7.6, Sleep ≤ 5 hr: OR, 1.33; 95% CI, 1.00–1.77
Spain and ≥ 10 hr/day 43.6% Sleep 8 hr: OR, 1.39; 95% CI, 1.11–1.75
Reference: 7 hr/day ORs of severe obesity
Sleep ≤ 5 hr: OR, 2.08; 95% CI, 1.31–3.32
Sleep 8 hr: OR, 1.82; 95% CI, 1.21–2.73
Sleep 9 hr: OR, 1.57; 95% CI, 1.00–2.47
Weight gain ≥ 5 kg
In women sleeping ≤ 5 hr: OR, 3.41; 95% CI, 1.34–8.69
In women sleeping 8 hr: OR, 3.03; 95% CI, 1.29–7.12
In women sleeping 9 hr: OR, 3.77; 95% CI, 1.55–9.17
In total or men: no significant findings
Stranges et al. (2008)59 Prospective study White-collar British civil servants Short sleep: ≤ 5 hr/day Self-reported 35–55, 72.1% Changes in BMI
(follow-up: from the Whitehall II Study Normal sleep: 7 hr/day Short sleep: β, –0.06; 95% CI, –0.26–0.14
1997–1999 to (n= 10,308) Changes in WC
2003–2004)/the Short sleep: β, 0.44; 95% CI, –0.23–1.12
United Kingdom New-onset obesity
Short sleep: OR, 1.05; 95% CI, 0.60–1.82
Nishiura et al. (2010)60 Prospective study Nonobese Japanese male workers Short sleep: < 6 hr/day Self-reported 40–59, 100% New-onset obesity
(follow-up: 4 yr)/ (n= 2,632) Normal sleep: 7–7.9 hr/ Short sleep: OR, 2.46; 95% CI, 1.41–4.31
Japan day
(Continued to the next page)

J Obes Metab Syndr 2018;27:4-24

 Table 1. Continued
Type of study/ Study population Definition of sleep Method of sleep Age (yr) and
Author (year) Outcome
country or region (sample size) disturbances assessment male (%)
Watanabe et al. Prospective study Employees for an electric power Sleep duration was cate- Self-reported 39.8± 9.6, 86.3% Weight gain
(2010)61 (follow-up: 1 yr)/ company (n= 23,212) gorized as: < 5, 5–< 6, Male with sleep < 5 hr/day: β, 0.016; 95% CI, 0.024–0.146; P< 0.01
Japan 6–< 7, 7–< 8, 8–< 9, Male with sleep < 5 hr/day: β, 0.013; 95% CI, 0.001–0.061; P= 0.04
and ≥ 9 hr/day Male with sleep ≥ 9 hr/day: β, 0.018; 95% CI, 0.079–0.340; P< 0.01
Reference: 7–< 8 hr/day New-onset obesity
Ding C, et al. Sleep and Obesity

Male with sleep < 5 hr/day: OR, 1.91; 95% CI, 1.36–2.67
Male with sleep 5–6 hr/day: OR, 1.50; 95% CI, 1.24–1.80
No significant association between sleep duration and weight gain

J Obes Metab Syndr 2018;27:4-24

or obesity was found for women.
Itani et al. (2011)62 Prospective study Workers in a local government Short sleep: < 5 hr/day Self-reported NS, 95.4% New-onset obesity
(follow-up: 7 yr)/ organization (n= 22,743) Normal sleep: 5–7 hr/day Male subjects with short sleep: RR, 1.20; 95% CI, 1.09–1.32
Japan Female subjects with short sleep: RR, 1.71; 95% CI, 1.11–2.87
Lyytikäinen et al. Prospective study Middle-aged municipal employees Short sleep: ≤ 5 hr/day Self-reported 40–60, 18.5% Weight gain ≥ 5 kg
(2011)63 (follow-up: 5–7 yr)/ from the Helsinki Health Study Long sleep: ≥ 9 hr/day Female with short sleep: OR, 1.42; 95% CI, 1.01–2.01
Finland (n= 7,027) Reference: 7 hr/day Female with long sleep: OR, 1.30; 95% CI, 0.97–1.76
Male with short sleep: OR, 0.88; 95% CI, 0.44–1.74
Male with long sleep: OR, 1.06; 95% CI, 0.48–2.32
Kobayashi et al. Prospective study Healthy population (n= 11,136) Sleep duration was Self-reported ≥ 20, 44.0% Weight gain
(2012)64 (follow-up: 3 yr)/ categorized as: ≤ 5, 6, 7, Sleep ≤ 5: β coefficient, 0.03; 95% CI, 0.03–1.1; P= 0.02
Japan and ≥ 8 hr/day Sleep ≥ 8: β coefficient, 0.01; 95% CI, –0.03–0.1; P= 0.34
Reference: 7 hr/day New-onset obesity
Sleep ≤ 5: OR, 1.5; 95% CI, 1.1–2.0
Sleep ≥ 8: OR, 1.3; 95% CI, 0.9–1.8
Yiengprugsawan et al. Prospective study Distance learners at Sukhothai Sleep duration was Self-reported 35.6 (20–49), 45.2% Overweight
(2012)65 (follow-up: 4 yr)/ Thammathirat Open University categorized as < 6, 6, 7, Female with short sleep: OR, 1.33; 95% CI, 1.18–1.51
Thailand (n= 60,569) 8 and ≥ 9 hr/day; Female with long sleep: OR, 1.22; 95% CI, 1.07–1.39
Short sleep: < 6 hr/day Male with short sleep: OR, 1.13; 95% CI, 1.00–1.28
Long sleep: ≥ 9 hr/day Male with long sleep: OR, 1.03; 95% CI, 0.91–1.16
Reference: 7 hr/day New-onset obesity
Female with short sleep: OR, 1.49; 95% CI, 1.32–1.68
Female with long sleep: OR, 1.36; 95% CI, 1.20–1.53
Male with short sleep: OR, 1.36; 95% CI, 1.21–1.52
Male with long sleep: OR, 1.16; 95% CI, 1.03–1.30
Nagai et al. (2013)66 Prospective study General population (n= 9,658) Short sleep: ≤ 5 hr/day Self-reported 40–79, NS Weight gain ≥ 5 kg
(follow-up: 11 yr)/ Long sleep: ≥ 9 hr/day Total subjects with short sleep: OR, 0.93; 95% CI, 0.73–1.20
Japan Reference: 7 hr/day Total subjects with long sleep: OR, 1.05; 95% CI, 0.91–1.20
BMI ≥ 25 kg/m2 with short sleep: OR, 0.86; 95% CI, 0.58–1.29
BMI ≥ 25 kg/m2 with long sleep: OR, 1.36; 95% CI, 1.09–1.70
New-onset obesity
Short sleep: OR, 1.08; 95% CI, 0.77–1.51
Long sleep: OR, 1.06; 95% CI, 0.86–1.29
(Continued to the next page)

http://www.jomes.org | 9
 Table 1. Continued
Type of study/ Study population Definition of sleep Method of sleep Age (yr) and
Author (year) Outcome
country or region (sample size) disturbances assessment male (%)
Ohkuma et al. (2013)67 Cross-sectional Japanese patients with T2DM Sleep duration was Self-reported ≥ 20, 57% ORs (95% CIs) for obesity
study/Japan (n= 4,870) categorized as: Sleep < 4.5 hr/day: OR, 1.78; 95% CI, 1.26–2.52
< 4.5, 4.5–5.4, 5.5–6.4, Sleep ≥ 8.5 hr/day: OR, 1.24; 95% CI, 0.97–1.58
6.5–7.4, 7.5–8.4, and P for quadratic trend: < 0.001
≥ 8.5 hr/day;
Ding C, et al. Sleep and Obesity

Reference: 6.5–7.4 hr/day

Sayón-Orea et al. Prospective study General population from the SUN Sleep duration was Self-reported 39± 12, NS New-onset obesity

10 | http://www.jomes.org
(2013)68 (median follow-up: Mediterranean Cohort (n= 10,532) categorized as < 5, Total with sleep < 5 hr/night: HR, 1.94; 95% CI, 1.19–3.18
6.5 yr)/Spain 5–< 7, 7– < 8, ≥ 8 hr/ Male with sleep < 5 hr/night: HR, 2.09; 95% CI, 1.18–3.69
night; Reference: 7–< 8 Female with sleep < 5 hr/night: HR, 1.26; 95% CI, 0.44–3.57
hr/day Total with sleep ≥ 8 hr/night: HR, 1.13; 95% CI, 0.89–1.43
Male with sleep ≥ 8 hr/night: HR, 0.88; 95% CI, 0.64–1.21
Female with sleep ≥ 8 hr/night: HR, 1.43; 95% CI, 0.97–2.10
Xiao et al. (2013)69 Prospective study General population from the National Sleep duration was Self-reported 51–72, 51.8% Weight gain ≥ 5 kg
(follow-up: 7.5 yr)/ Institutes of Health-AARP Diet and categorized as Male with sleep < 5 hr/day: OR, 1.27; 95% CI, 1.07–1.52
the United States Health Study (n= 83,377) < 5, 5–6, 7–8, ≥ 9 hr/ Female with sleep < 5 hr/day: OR, 1.30; 95% CI, 1.12–1.51
day; Male with sleep ≥ 9 hr/day: OR, 1.16; 95% CI, 0.99–1.36
Reference: 7–8 hr/day Female with sleep ≥ 9 hr/day: OR, 1.02; 95% CI, 0.88–1.17
New-onset obesity
Male with sleep < 5 hr/day: OR, 1.45; 95% CI, 1.06–1.99
Female with sleep < 5 hr/day: OR, 1.37; 95% CI, 1.04–1.79
Sleep duration ≥ 9 hr/day
Male with sleep ≥ 9 hr/day: OR, 1.12; 95% CI, 0.84–1.49
Female with sleep ≥ 9 hr/day: OR, 0.91; 95% CI, NS
Vgontzas et al. (2014)70 Prospective study General population from the Penn Sleep duration was cate- Self-reported 48.9± 13.4, 50.5% New-onset obesity
(total follow-up: 7.5 State Cohort (n= 815) gorized as ≤ 5, 5–6, 6–7, (subjective) and Subjective sleep duration ≤ 5 hr/night: OR, 1.08; 95% CI, 0.48–2.41
yr; women: 4.5 yr; ≥ 7 hr/night; PSG (objective) Objective sleep duration ≤ 5 hr/night: OR, 0.51; 95% CI, 0.22–1.18
men: 10.5 yr)/ Reference: ≥ 7 hr/night
the United States
Gutiérrez-Repiso et al. Prospective study General population from the Pizarra Short sleep: ≤ 7 hr/night Self-reported 18–65, 38.8% ORs of becoming obese in subjects with short sleep
(2014)71 (follow-up: 11 yr)/ cohort study (n= 1,145) Normal sleep: ≥ 8 hr/night At the 6-yr follow-up: OR, 1.99; 95% CI, 1.12–3.55
Spain At the 11-yr follow-up: OR, 2.73; 95% CI, 1.47–5.04
Kim et al. (2015)72 Prospective study General population from the Short sleep: < 6 hr/day Self-reported 40–70, 41.1% New-onset metabolic syndrome
(follow-up: 2.6 yr)/ ARIRANG Study (n= 3,862) Long sleep: ≥ 10 hr/day Short sleep: OR, 1.41; 95% CI, 1.06–1.88
Korea Reference: 6–7.9 hr/day Long sleep: OR, 0.68; 95% CI, 0.39–1.17
High WC
Short sleep: OR, 1.30; 95% CI, 0.98–1.69
Long sleep: OR, 0.97; 95% CI, 0.62–1.50
(Continued to the next page)

J Obes Metab Syndr 2018;27:4-24

 Table 1. Continued
Type of study/ Study population Definition of sleep Method of sleep Age (yr) and
Author (year) Outcome
country or region (sample size) disturbances assessment male (%)
Zhang et al. (2015)73 Cross-sectional School-aged children (n= 3,086) Sleep duration was Self-reported 7–14, 52.1% Risk of being overweight/obese
study/China categorized as: ≤ 8.00, Weekdays sleep ≤ 8.00 hr/night: OR, 1.995; 95% CI, 0.917–4.219
8.01–9.00, 9.01–10.00, Weekends sleep ≤ 8.00 hr/night: OR, 2.691; 95% CI, 1.513–4.785
and > 10 hr/night; Long holidays sleep ≤ 8.00 hr/night: OR, 2.921; 95% CI, 1.630–5.323
Reference: > 10 hr/night Sleep compensation during weekends: OR, 1.197; 95% CI,
Ding C, et al. Sleep and Obesity

Sleep compensated group: 1.004–1.493

(weekend [or holiday] Sleep compensation during holidays: OR, 1.309; 95% CI,
sleep duration–weekday 1.052–1.630

J Obes Metab Syndr 2018;27:4-24

sleep duration)/weekday
sleep duration× 100%
≥ 10%
Reference:
noncompensated group
Sleep duration and risk of diabetes
Ayas et al. (2003)11 Prospective (mean Female married registered nurses Short sleep: ≤ 5 hr/day Self-reported 40–65, 0% New-onset symptomatic diabetes
follow-up: 10 yr)/ from the Nurses’ Health Study Long sleep: ≥ 9 hr/day Short sleep: RR, 1.34; 95% CI, 1.04–1.72
the United States (n= 70,026) Reference: 8 hr/day Long sleep: RR, 1.35; 95% CI, 1.04–1.75
Mallon et al. (2005)74 Prospective (mean General population (n= 1,170) Short sleep: ≤ 5 hr/night Self-reported 45–65, 47.0% New-onset diabetes
follow-up: 12 yr)/ Long sleep: ≥ 9 hr/night Male with short sleep: RR, 2.8; 95% CI, 1.1–7.3
Sweden Reference: 5–8 hr/night Female with short sleep: RR, 1.8; 95% CI, 0.5–6.8
Male with long sleep: NS
Female with long sleep: RR, 2.9; 95% CI, 0.6–15.0
Yaggi et al. (2006)75 Prospective study Men from the Massachusetts Male Average sleep duration Self-reported 40–70, 100% New-onset diabetes
(follow-up: 15–17 Aging Study without diabetes was divided into: ≤ 5, 6, Sleep ≤ 5 hr/night: RR, 1.95; 95% CI, 0.95–4.01
yr)/the United (n= 1,139) 7, 8, and > 8 hr/night; Sleep > 8 hr/night: RR, 3.12; 95% CI, 1.53–6.37
States Reference: 7 hr/night Further adjusted for testosterone
Sleep ≤ 5 hr/night: RR, 1.51; 95% CI, 0.71–3.19
Sleep > 8 hr/night: RR, 2.81; 95% CI, 1.34–5.90
Gangwisch et al. Prospective study General population from the First Short sleep: ≤ 5 hr/night Self-reported 32–86, 37% New-onset diabetes
(2007)76 (follow-up: 8-10 yr)/ National Health and Nutrition Long sleep: ≥ 9 hr/night Short sleep: OR, 1.47; 95% CI, 1.03–2.09
the United States Examination Survey I (n= 8,992) Reference: 7 hr/night Long sleep: OR, 1.52; 95% CI, 1.06–2.18
Hayashino et al. Prospective study Asian workers from High-risk and Short sleep: sleep duration Self-reported 38.2 (19–69), 73.9% New-onset diabetes
(2007)77 (median follow-up: Population Strategy for < 6 hr/day Short sleep: HR, 1.15; 95% CI, 0.76–1.74
4.2 yr)/Japan Occupational Health Promotion Long sleep: ≥ 9 hr/day Long sleep: HR, 1.03; 95% CI, 0.62–1.70
Study (n= 6,509) Reference: 6–7 hr/day
Beihl et al. (2009)78 Prospective study General population from the Insulin Short sleep: ≤ 7 hr/night Self-reported 40–69, 43.3% New-onset diabetes
(follow-up: 5 yr)/the Resistance Atherosclerosis Study Long sleep: ≥ 9 hr/night Non-Hispanic whites and Hispanics with short sleep: OR, 2.36; 95%
United States (n= 900) Reference: 8 hr/night CI, 1.11–5.00
Non-Hispanic whites and Hispanics with long sleep: OR, 2.15; 95%
CI, 0.50–9.30
African American with short sleep: OR, 0.63; 95% CI, 0.14–2.90
African American with long sleep: OR, 0.39; 95% CI, 0.02–7.19
(Continued to the next page)

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 Table 1. Continued
Type of study/ Study population Definition of sleep Method of sleep Age (yr) and
Author (year) Outcome
country or region (sample size) disturbances assessment male (%)
Chaput et al. (2009)79 Longitudinal study General population from the Quebec Short sleep: ≤ 6 hr/night Self-reported 21–64, 42.4% New-onset T2DM or IGT
(mean follow-up: Family Study (n= 276) Long sleep: ≥ 9 hr/night Short sleep: OR, 2.42; 95% CI, 1.49–3.33
6.0± 0.9 yr)/Canada Reference: 7–8 hr/night Long sleep: OR, 2.31; 95% CI, 1.41–3.15
Xu et al. (2010)80 Prospective study General population from the National Average sleep duration Self-reported 50–71, 56.8% New-onset diabetes
(follow-up: 6 yr)/the Institutes of Health-American was divided into: < 5, Sleep < 5 hr/night: OR, 1.34; 95% CI, 1.20–1.50
Ding C, et al. Sleep and Obesity

United States Association of Retired Persons Diet 5–6, 7–8, and ≥ 9 hr/ Sleep 5–6 hr/night: OR, 1.06; 95% CI, 1.01–1.11
and Health cohort (n= 164,399) night; Sleep ≥ 9 hr/night: OR, 1.09; 95% CI, 0.97–1.22

12 | http://www.jomes.org
Reference: 7–8 hr/night Day napping < 1 hr/day: OR, 1.23; 95% CI, 1.18–1.29
Day napping was Day napping ≥ 1 hr/day: OR, 1.55; 95% CI, 1.45–1.66
categorized as: none, Hours of day napping× night sleep on diabetes: P< 0.0001;
< 1 hr, and ≥ 1 hr/day; among participants with no napping, only short night sleeping was
Reference: none associated with higher occurrence of diabetes (OR, 1.32), whereas
among those with ≥ 1 hr of napping, both long (OR, 1.55) and short
(OR, 1.78) sleeping was associated with higher risk.
Kita et al. (2012)81 Prospective, Local government employees Short sleep: ≤ 5 hr/day Self-reported 35–55, 79.0% New-onset diabetes
occupational-based (n= 3,570) Reference: > 7 hr/day Short sleep: OR, 5.37; 95% CI, 1.38–20.91
study (follow-up: 4
yr)/Japan
von Ruesten et al. Prospective study General population from the Short sleep: < 6 hr/day Self-reported 35–65, 38.6% New-onset diabetes
(2012)82 (mean follow-up: European Prospective Investigation Long sleep: ≥ 9 hr/day Short sleep: HR, 1.06; 95% CI, 0.80–1.40
7.8 yr)/Germany into Cancer and Nutrition-Potsdam Reference: 7–< 8 hr/day Long sleep: HR, 1.05; 95% CI, 0.82–1.33
Study (n= 23,620)
Holliday et al. (2013)83 Prospective study General population from the 45 and Average sleep duration Self-reported ≥ 45, 47.3% New-onset diabetes
(mean follow-up: Up Study (n= 212,388) was categorized as: < 6, Sleep < 6 hr: HR, 1.29; 95% CI, 1.08–1.53
2.3 yr)/Australia 6–< 7, 7–< 8, 8–< 9, Sleep ≥ 10 hr: HR, 1.03; 95% CI, 0.88–1.19
9–< 10, and ≥ 10 hr/
day;
Reference: 7–< 8 hr/day
Gutiérrez-Repiso et al. Prospective study General population from the Pizarra Short sleep: ≤ 7 hr/night Self-reported 18–65, 38.8% New-onset diabetes
(2014)71 (follow-up: 11 yr)/ cohort study (n= 1,145) Reference: ≥ 8 hr/night At the 6-yr follow-up, short sleep: OR, 1.96; 95% CI, 1.10–3.50
Spain At the 11-yr follow-up, short sleep: OR, 1.28; 95% CI, 0.60–2.69
Heianza et al. (2014)84 Prospective study Workers (n= 38,987) Average sleep duration Self-reported 18–83, 64.2% New-onset diabetes
(follow-up: 8 yr)/ was categorized as: Sleep < 5.5 hr: OR, 1.53; 95% CI, 1.19–1.97
Japan < 5.5, 5.5–< 6.5, 6.5– Sleep 5.5–< 6.5 hr: OR, 1.25; 95% CI, 1.10–1.42
< 7.0, 7.0–7.5, > 7.5– Sleep > 8 hr/day: OR, 1.03; 95% CI, 0.81–1.30
8.0, or > 8.0 hr/day; In age ≤ 45 yr, sleep < 5.5 hr: OR, 1.61; 95% CI, 1.08–2.42
Short sleep: < 5.5 or 5.5– In age 46–59 yr, sleep < 5.5 hr: OR, 1.56; 95% CI, 1.10–2.22
< 6.5 hr/day; In age ≥ 60 yr, sleep < 5.5 hr: OR, 1.72; 95% CI, 0.75–3.92
Reference: 7.0–7.5 hr/day
Lou et al. (2015)85 Prospective study General population (n= 11,842) Short sleep: ≤ 6 hr/night Self-reported 44.8± 14.7, 45.4% New-onset T2DM
(median follow-up: Long sleep: ≥ 8 hr/night Short sleep: RR, 1.67; 95% CI, 1.34–2.16
5 yr)/China Reference: 6–8 hr/night Long sleep: RR, 1.45; 95% CI, 1.02–1.77
(Continued to the next page)

J Obes Metab Syndr 2018;27:4-24

 Table 1. Continued
Type of study/ Study population Definition of sleep Method of sleep Age (yr) and
Author (year) Outcome
country or region (sample size) disturbances assessment male (%)
Kim et al. (2015)72 Prospective study General population (n= 3,862) Short sleep: < 6 hr/day Self-reported 40–70, 41.1% High blood glucose
(follow-up: 2.6 yr)/ Long sleep: ≥ 10 hr/day Short sleep: OR, 1.31; 95% CI, 0.96–1.79
Korea Reference: 6–7.9 hr/day Long sleep: OR, 0.56; 95 CI, 0.29–1.04
Han et al. (2016)86 Prospective Study Retired employees from the Sleep duration was Self-reported 62.5, 43.2% New-onset diabetes
(follow-up: 3–4.75 Dongfeng-Tongji cohort (n= 16,399) categorized as: < 7, Sleep < 7 hr/night: HR, 0.93; 95% CI, 0.72–1.19
yr)/China 7–< 8 (reference), Sleep ≥ 10 hr/night: HR, 1.42; 95% CI, 1.08–1.87
Ding C, et al. Sleep and Obesity

8–< 9, 9– < 10, Napping > 90 min: HR, 1.28; 95% CI, 1.03–1.59
and ≥ 10 hr/night; Sleep duration ≥ 10 hr/night and napping > 60 min: HR, 1.72; 95%

J Obes Metab Syndr 2018;27:4-24

afternoon napping was CI, 1.03–2.85
divided into: no napping
(0 min, reference), 1–30,
31–60, 61–90, and > 90
min
Sleep duration and glycemic control
Knutson et al. (2006)87 Cross-sectional African-American women and men Perceived sleep debt: the Self-reported 57± 12, 26.1% Glycemic control (lnHbA1c)
study/the United with diabetes (n= 161) difference between Sleep debt in patients without diabetic complications: β, 0.51;
States weekday sleep duration P= 0.04
and preferred sleep Sleep debt in patients with 1 or more diabetic complications:
duration β, −0.005; P= 0.85
Kim et al. (2013)88 Cross-sectional Korean patients with diabetes Sleep duration was Self-reported 61.7± 12.3, 49.9% OR of high HbA1c (≥ 7.0%)
study/Korea (n= 2,134) categorized as: < 6, 6, 7, Total with sleep < 6 hr/day: OR, 1.15; 95% CI, 0.85–1.60
8, and ≥ 9 hr/day; Total with sleep ≥ 9 hr/day: OR, 1.38; 95% CI, 0.93–2.03
Reference: 7 hr/day Female with sleep < 6 hr/day: OR, 1.46; 95% CI, 0.96–2.21
Female with sleep ≥ 9 hr/day: OR, 1.31; 95% CI, 0.75–2.27
Age < 65 yr with sleep < 6 hr/day: OR, 1.34; 95% CI, 0.86–2.09
Age < 65 yr with sleep ≥ 9 hr/day: OR, 1.33; 95% CI, 0.84–2.41
Ohkuma et al. (2013)67 Cross-sectional Japanese patients with T2DM Sleep duration was cate- Self-reported ≥ 20, 57% Adjusted geometric means (95% CIs) of HbA1c
study/Japan (n= 4,870) gorized as: < 4.5, Sleep < 4.5 hr/day: 7.52 (7.38–7.67)
4.5–5.4, 5.5–6.4, Sleep 6.5–7.4 hr/day: 7.32 (7.28–7.37)
6.5–7.4, 7.5–8.4, and Sleep ≥ 8.5 hr/day: 7.43 (7.34–7.52)
≥ 8.5 hr/day P for quadratic trend: 0.004
Wang et al. (2015)89 Cross-sectional Patients with diabetes from the Sleep duration was Self-reported Sleep < 6 hr/night: Poor glycemic control (HbA1c ≥ 7.0%)
study/China baseline survey of the REACTION categorized as: < 6, 61.2± 8.8, 37%; Sleep < 6 hr/night: OR, 1.09; 95% CI, 0.99–1.21
Study (n= 56,032) 6–7.9, 8–8.9, and ≥ 9 Sleep ≥ 9 hr/night: Sleep ≥ 9 hr/night: OR, 1.11; 95% CI, 1.05–1.18
hr/night; 61.4± 9.7, 38%;
Reference: 6–7.9 hr/night Reference:
60.5± 8.8, 39%
Kong et al. (2017)90 Cross-sectional Hong Kong Chinese patients with Sleep duration: the period Self-reported 53.9± 8.7, 59% Sleep duration difference between weekdays and weekends is curvi-
study/Hong Kong T2DM (n= 3,508) between bedtime and linearly associated with both HbA1c and FPG.
wake-up time on One hour more sleep during weekends than weekdays was associat-
weekdays and ed with a decrease in HbA1c (–0.13%; 95 % CI, –0.24 to –0.02).
weekends
Values are presented as range, mean± standard deviation, or mean (range).
RR, relative risk; CI, confidence interval; HR, hazard ratio; OR, odds ratio; NS, not specified; BMI, body mass index; WC, waist circumference; T2DM, type 2 diabetes mellitus; PSG, polysomnography; IGT, impaired glucose toler-

http://www.jomes.org | 13
ance; FPG, fasting plasma glucose.
 Table 2. Clinical studies examining the association between sleep quality with obesity and diabetes
Type of study/ Study population Method of sleep Age (yr) and
Author (year) Definition of sleep disturbances Outcome
country or region (sample size) assessment male (%)
Sleep quality and weight gain/obesity
Lyytikäine Prospective study (follow-up: Middle-aged municipal Trouble falling asleep, waking up Self-reported 40–60, 18.5% Weight gain of ≥ 5 kg
et al. 5–7 yr)/Finland employees from the several times per night, trouble (the Jenkins Female with trouble falling asleep: OR, 1.49; 95% CI, 1.09–2.03
(2011)91 Helsinki Health Study staying asleep, or waking up early Sleep Female with waking up several times per night: OR, 1.34; 95% CI,
(n= 7,022) feeling tired: the corresponding Questionnaire) 1.09–1.65
sleep problems ≥ 15 nights in the Female with trouble staying asleep: OR, 1.29; 95% CI, 1.02–1.62
Ding C, et al. Sleep and Obesity

past 4 weeks Female with waking up tired: OR, 1.04; 95% CI, 0.83–1.30

14 | http://www.jomes.org
Male: NS
Huang et al. Cross-sectional study/China Patients with insomnia Slow wave sleep time and rapid eye PSG Insomnia: BMI
(2013)92 (n= 141) movement sleep time 42.2± 9.8, 44% Slow wave sleep time (min): β, –0.013; 95% CI, –0.026 to –0.001;
Healthy: 38.9± 12.4, P= 0.043
51% Rapid eye movement sleep time (min): β, 0.007; 95% CI, –0.008 to
0.023; P= 0.352
Piccolo et al. Prospective study (follow-up: General population from the Restless sleep: experiencing Self-reported 30–79, NS New-onset obesity
(2013)93 4.8± 0.6 yr)/the United Boston Area Community restless sleep much of the time Experiencing restless sleep: OR, 1.66; 95% CI, 1.10–2.49
States Health Survey (n= 4,145) during the past week
Sivertsen Prospective study (follow-up: General population from the Insomnia: “often” or “almost every Self-reported 32–66, 43.1% New-onset obesity
et al. 11 yr)/Norway Nord-Trøndelag Health night” had difficulties in initiating Insomnia: OR, 1.13; 95% CI, 0.96–1.33
(2014)94 Studies (n= 24,715) or maintaining sleep in the preced-
ing month, in addition to reporting
impaired work performance caused
by insomnia during the preceding
year
Vgontzas Prospective study General population (n= 815) Insomnia: a complaint of insomnia Self-reported 48.9± 13.4, 50.5% New-onset obesity
et al. (total follow-up: 7.5 yr; with a duration of ≥ 1 yr Insomnia with adjustment for subjective sleep duration: OR, 0.48;
(2014)70 women: 4.5 yr; men: 10.5 Poor sleep: a moderate-to-severe 95% CI, 0.15–1.53
yr)/the United States complaint of difficulty falling Poor sleep with adjustment for subjective sleep duration: OR, 1.78;
asleep, difficulty staying asleep, 95% CI, 1.02–3.13
early morning awakening, or Insomnia with adjustment for objective sleep duration: OR, 0.59;
non-restorative sleep. Normal 95% CI, 0.20–1.77
sleep: absence of either of these Poor sleep with adjustment for objective sleep duration: OR, 1.76;
two categories. 95% CI, 1.03–3.00
Tan et al. Cross-sectional study/Finland Overweight middle-aged OSA: an AHI of 5 or greater with EDS Specialist 30–65, 100% BMI
(2015)95 men (n= 211) or an AHI of 15 or greater, physician Reference, 15.8± 4.3; OSA, 19.7± 6.0 (P< 0.05); insomnia, 18.5± 5.9;
regardless of associated symptoms diagnosis OSA+insomnia, 19.7± 7.1 (P< 0.05)
Insomnia: DIS and/or DMS and/or (through Waist circumference (cm)
NRS, and lasted for at least 1 Vitalmed sleep Reference, 98.0± 7.6; OSA, 110.4± 9.0 (P< 0.05); insomnia,
month during the last 3 months questionnaire 106.5± 10.2 (P< 0.05); OSA+insomnia, 111.4± 14.7 (P< 0.05)
Reference: overweight participants and PSG) Fat mass trunk (kg)
free from any sleep disorders Reference, 15.8± 4.3; OSA, 19.7± 6.0 (P< 0.05); insomnia, 18.5± 5.9
(P< 0.05); OSA+insomnia, 19.7± 7.1 (P< 0.05)
Fat mass android region (kg)
Reference, 2.9± 0.9; OSA, 3.7± 1.1 (P< 0.05); insomnia, 3.5± 1.2
(P< 0.05); OSA+insomnia, 3.8± 1.4 (P< 0.05)

J Obes Metab Syndr 2018;27:4-24

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 Table 2. Continued
Type of study/ Study population Method of sleep Age (yr) and
Author (year) Definition of sleep disturbances Outcome
country or region (sample size) assessment male (%)
Sleep quality and risk of diabetes
Nilsson et al. Prospective study (mean Healthy men from the Malmo Sleep disturbances: had either or Self-reported 35–51, 100% New-onset diabetes
(2004)96 follow-up: 14.8± 2.4 yr)/
Preventive Project both positive reply to difficulty in questionnaire Sleep disturbances: OR, 1.52; 95% CI, 1.05–2.20
Sweden (n= 6,599) falling asleep or generally use
sleeping pills more than 3 times a
week
Ding C, et al. Sleep and Obesity

Björkelund Prospective study (follow-up: Swedish women from the Sleep complaints: sleep problems Self-reported 70–92, 0% New-onset diabetes
et al. 32 yr)/Sweden Population Study of (without specified time frame) and/ Sleep complaints: RR, 1.04; 95% CI, 0.91–1.18

J Obes Metab Syndr 2018;27:4-24

(2005)97 Women in Gothenburg or having consulted a doctor for
(n= 661) sleep problems and/or hospital ad-
mission for this reason
Mallon et al. Prospective study (mean General population DIS: had severe difficulties (scores 4 Self-reported 45–65, 47.0% New-onset diabetes
(2005)74 follow-up: 12 yr)/Sweden (n= 1,170) and 5) in initiating sleep (the Uppsala Male with DIS: RR, 2.4; 95% CI, 0.7–8.6
DMS: had severe difficulties (scores Sleep Invento- Male with DMS: RR, 4.8; 95% CI, 1.9–12.5
4 and 5) in maintaining sleep ry) Female with DIS: NS
Female with DMS: RR, 1.8; 95% CI, 0.5–6.0
Meisinger Prospective study (mean General population DIS: often had trouble falling asleep Self-reported 25–74, 49.9% New-onset diabetes
et al. follow-up: 7.5 yr)/Germany (n= 8,269) DMS: often woke up during the night Male with DIS: HR, 1.10; 95% CI, 0.59–2.03
(2005)98 Female with DIS: HR, 1.42; 95% CI, 0.81–2.50
Male with DMS: HR, 1.60; 95% CI, 1.05–2.45
Female with DMS: HR, 1.60; 95% CI, 1.05–2.45
Hayashino Prospective study (median Asian healthy workers from DIS: sometimes or often had Self-reported 38.2 (19–69), 73.9% New-onset diabetes
et al. follow-up: 4.2 yr)/Japan High-risk and Population difficulties initiating sleeping Sometimes DIS: HR, 1.42; 95% CI, 1.05–1.91
(2007)77 Strategy for Occupational DMS: sometimes or often had Often DIS: HR,1.61; 95% CI, 1.00–2.58
Health Promotion Study difficulties maintaining sleeping Sometimes DMS: HR, 1.31; 95% CI, 0.97–1.76
(n= 6,509) Often DMS: 1.37; 95% CI, 0.87–2.16
Kita et al. Prospective, Local government employees Any sleep difficulties participants Self-reported 35–55, 79.0% New-onset diabetes
(2012)81 occupational-based study (n= 3,570) may have experienced ≥ 3 times a questionnaire Awakening during the night: OR, 5.03; 95% CI, 1.43–17.64
(follow-up: 4 yr)/Japan week during the previous month in Self-perceived insufficient sleep duration: OR, 6.76; 95% CI, 2.09–
sleep induction, awakening during 21.87
the night, early morning awaken- Unsatisfactory overall quality of sleep: OR, 3.71; 95% CI, 1.37–10.07
ing, self-perceived insufficient
sleep duration, and overall quality
of sleep
Piccolo et al. Prospective study (mean General population from the Restless sleep: experiencing restless Self-reported 30–79, NS New-onset T2DM
(2013)93 follow-up: 4.8± 0.6 yr)/ Boston Area Community sleep much of the time during the Restless sleep: OR, 1.05; 95% CI, 0.67–1.64
the United States Health Survey (n= 4,145) past week
Sivertsen Prospective study (follow-up: General population from the Insomnia: “often” or “almost every Self-reported 32–66, 43.1% New-onset T2DM
et al. 11 yr)/Norway Nord-Trøndelag Health night” had difficulties in initiating Insomnia: OR, 1.07; 95% CI, 0.82–1.41
(2014)94 Studies (n= 24,715) or maintaining sleep in the preced-
ing month, in addition to reporting
impaired work performance caused
by insomnia during the preceding
year

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(Continued to the next page)
 Table 2. Continued
Type of study/ Study population Method of sleep Age (yr) and
Author (year) Definition of sleep disturbances Outcome
country or region (sample size) assessment male (%)
Lou et al. Prospective study (follow-up: General population Poor sleep: had difficulties with Self-reported 44.8± 14.7, 45.4% New-onset T2DM
(2015)85 5 yr)/China (n= 11,842) initiating and maintaining sleep ≥ 8 Poor sleep quality: RR, 1.91; 95% CI, 1.31–2.74
days per month on average during Poor sleep quality with short sleep duration (≤ 6 hr/night): RR, 6.21;
the previous year 95% CI, 2.78–11.81
Lee et al. Prospective study (median General population from the Poor sleep quality: the score of the Self-reported 10–75, 45.6% New-onset T2DM
Ding C, et al. Sleep and Obesity

(2016)99 follow-up period: 2.5 yr)/ family cohort study in PSQI ≥ 5 RR, 2.64; 95% CI, 1.03–6.78
Korea primary care (the FACTS)

16 | http://www.jomes.org
(n= 563)
Sleep quality and glycemic control
Knutson et al. Cross-sectional study/ African-American women Modified PSQI score: PSQI score Self-reported 57± 12, 26.1% Glycemic control (lnHbA1c)
(2006)87 the United States and men with diabetes after removing the sleep duration questionnaire Modified PSQI score in patients without diabetic complications:
(n= 161) component to assess sleep quality β, −0.014; P= 0.16
independently from sleep quantity Modified PSQI score in patients with at least 1 diabetic
complications: β, 0.043; P= 0.002
Wan Mah- Cross-sectional study/Ireland Caucasian patients with Poor sleep quality: the score of PSQI Self-reported NS, 54.4% Log HbA1c
mood et al. T2DM (n= 114) >5 questionnaire Poor sleep quality: β, 0.038; P= 0.826
(2013)100
Cho et al. Cross-sectional study/Korea Patients with T2DM (n= 614) Sleep apnea: SDQ-SA ≥ 36 for males Self-reported 59.7± 11.1, 62.1% Postprandial glucose
(2014)101 and ≥ 32 for females; questionnaires Sleep apnea score (SDQ-SA): r= 0.100, P= 0.032
Poor sleep: PSQI score ≥ 5 HbA1c
Insomnia: any difficulty in falling No significant association between HbA1c values and poor sleep,
asleep, maintaining sleep, early insomnia
morning waking, and
non-restorative sleep occurring at
least three times per week over the
preceding month
Nefs et al. Cross-sectional study/the Dutch adults with T1DM Poor sleep quality: PSQI score > 5 Self-reported T1DM: 47± 16, 41% Most recent HbA1c, % (mmol/mol)
(2015)102 Netherlands (n= 267) or T2DM (n= 361), questionnaire T2DM: 62± 9, 54% In T1DM, good sleep quality vs. poor sleep quality: 7.5± 0.9 (58± 10)
(total n= 628) vs. 7.5± 1.1 (59± 12), P= 0.68;
In T2DM, good sleep quality vs. poor sleep quality: 7.1± 1.3 (54± 14)
vs. 7.3± 1.3 (57± 14), P= 0.09
Osonoi et al. Cross-sectional study/Japan Patients with T2DM (n= 724) Poor sleep quality: PSQI score ≥ 9 Self-reported 57.8± 8.6, 62.9% Fasting blood glucose (mg/dL)
(2015)103 Average sleep quality: PSQI score questionnaire Good sleep: 132± 31; average sleep: 136± 31; poor sleep: 141± 32
6–8 (P> 0.05)
Good sleep quality: PSQI score ≤ 5 HbA1c (%)
Good sleep: 6.9± 1.0; average sleep: 7.1± 1.1; poor sleep: 7.1± 0.8;
(P> 0.05)
Values are presented as range or mean± standard deviation.
OR, odds ratio; CI, confidence interval; NS, not specified; PSG, polysomnography; BMI, body mass index; OSA, obstructive sleep apnea; AHI, apnea hypopnea index; EDS, excessive daytime sleepiness; DIS, difficulty in initiating
sleep; DMS, difficulty in maintaining sleep; NRS, nonrestorative sleep; RR, relative risk; HR, hazard ratio; T2DM, type 2 diabetes mellitus; PSQI: the Pittsburgh Sleep Quality Index; SDQ-SA, the Sleep Disorders Questionnaire
Sleep Apnea subscale; T1DM, type 1 diabetes mellitus.

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Ding C, et al. Sleep and Obesity

sleep (NRS) is also suggested by the International Classification of reported that insomnia was associated with an 18% increased risk
Sleep Disorders as a subtype of insomnia. 104
(95% CI, 1.06–1.33) of incident obesity after 11 years of follow up,
Although the pathophysiology of insomnia is still not fully un- which was independent of baseline demographics, anxiety and de-
derstood, it has long been considered to be a disorder of hyper- pression. However, this association was negated when further ad-
arousal during both daytime and nighttime, which is associated justed for other comorbidities, such as angina, T2DM and hyper-
with increased activation of whole-body and brain metabolism, hy- tension (OR, 1.09; 95% CI, 0.97–1.24).94 Taken together, these in-
peractivity of HPA axis and hormonal dysregulation.49 A study in- conclusive results may be related to the adoption of different defini-
volving 1,042 monozygotic and 828 dizygotic twin pairs demon- tions of insomnia and obesity.
strated a 10% phenotypic correlation between insomnia and obesi- Although conflicting results have been reported for obesity, it ap-
ty, suggesting a shared genetic mechanism that underlies these con- pears that most studies support an association between insomnia
ditions. However, the findings about this association were incon-
105
and diabetes risk. In a meta-analysis of 107,756 participants from
sistent in other clinical studies, which mostly reported either no as- 13 independent cohorts, those with insomnia had stronger associa-
sociation or an inverse relationship between insomnia and BMI. In tion with incident diabetes (DIS: RR, 1.57; 95% CI, 1.25–1.97;
a cross-sectional study conducted in 211 Finnish men aged 30–65 DMS: RR, 1.84; 95% CI, 1.39–2.43), compared with participants
years, among the overweight or obese participants (n = 163), those with short sleep duration of ≤ 5–6 hours per night (RR, 1.28; 95%
with insomnia (n = 40) had higher fat mass in the trunk and an- CI, 1.03–1.60).106 In another larger meta-analysis of nearly 1.1 mil-
droid regions than the group without sleep disorder (n = 76, lion participants from 36 studies, insomnia (RR, 1.38; 95% CI,
P < 0.05), but no between-group differences in BMI or total fat 1.18–1.62) and its subtypes (DIS: RR, 1.55; 95% CI, 1.23–1.95;
mass. There was also no difference in BMI when comparing 141
95
DMS: RR, 1.72; 95% CI, 1.45–2.05) also demonstrated an inde-
Chinese patients with primary insomnia with 55 healthy volunteers pendent association with excess risk of developing diabetes.107
(22.54± 2.76 kg/m2 vs. 22.84 ± 3.28 kg/m2, P= 0.526).92 However, Short sleep duration with coexistent insomnia may further ag-
this study found that among patients with insomnia, there was a gravate the risk of future diabetes. In the Penn State Cohort of
significant negative correlation between the amount of SWS and 1,741 participants, participants with insomnia and sleep curtail-
BMI after controlling for potential confounders (β, –0.013; 95% ment ( < 5-hour per day) had an OR of 2.95 (95% CI, 1.24–7.03)
confidence interval [CI], –0.026 to –0.001; P = 0.043), suggesting for diabetes after adjustment for age, race, sex, BMI, smoking, alco-
that impaired sleep quality in subjects with insomnia may be the hol use, depression and sleep-disordered breathing, compared with
culprit linking insomnia with obesity. By contrast, some researchers those who had > 6-hour sleep per day and without insomnia.108
had reported positive relationships between insomnia and obesity Conversely, in the retrospective Freiburg Insomnia Cohort involv-
indices. The prospective Helsinki Health Study which included ing 328 patients with primary insomnia (203 women and 125
7,022 middle-aged respondents demonstrated that DIS (odds ratio men; mean age, 44.3 ± 12.2 years), those with concomitant short
[OR], 1.65; 95% CI, 1.22–2.22) and DMS (OR, 1.41; 95% CI, sleep duration did not have increased risk of T2DM (OR, 1.39;
1.13–1.75) were associated with a weight gain of 5 kg or more after 95% CI, 0.34–5.67 for first night of short sleep and OR, 2.30; 95%
5 to 7 years of follow-up, being more evident in women than in CI, 0.48–10.96 for second night of short sleep), perhaps due to a
men. In the prospective Penn State Cohort involving 815 non-
91
small number of patients with T2DM (n = 9).109 Indeed, there are
obese adults with a follow-up duration of 7.5 years, a moderate to possible pathogenetic mechanisms underpinning the link between
severe complaint of any DIS, DMS, EMA, or NRS was associated insomnia and risk of diabetes, including reduction of glucose toler-
with an increased incidence of obesity (OR, 1.76–1.78), while in- ance40, alteration of HPA axis and sympathetic nervous system110,
somnia tended towards significance after adjusted for sleep dura- and elevated markers of chronic inflammation.111 Hence, well-de-
tion, emotional stress, and other potential confounders.70 Another signed studies with sufficient sample size are required to unravel
prospective study conducted in Norwegian population (n= 24,715) the relationship between insomnia and diabetes.

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Ding C, et al. Sleep and Obesity

SLEEP AND GENES REGULATING THE may have high melatonin level that interacts with dietary intake,
CIRCADIAN CLOCK with subsequent impairment in glucose metabolism and increased
risk of T2DM.23
Clock genes may play a key role in linking sleep and the effect of Conditions that are often associated with circadian misalignment
circadian disruptions on metabolic functions. A central clock
23
are shift work and trans-meridian air travel (jet lag). Shift work can
which is located within the suprachiasmatic nuclei of the hypothal- desynchronize the central and peripheral circadian clocks, which
amus orchestrates the environmental light/dark cycles with human further perturbs the glucose metabolism by decreasing insulin sen-
physiology and behavior. Genetic or environmental perturbations sitivity, independent of sleep curtailment.23,115 In healthy adults,
of this synchronized molecular mechanism can lead to metabolic 3-week sleep curtailment with concomitant circadian misalignment
disturbances. In the core clock mechanism, the brain and muscle is demonstrated to reduce the resting metabolic rate and impair
Arnt like protein-1 (BMAL1)/circadian locomotor output cycles pancreatic beta-cell secretion.116 In mice model, chronic jet lag dis-
kaput (CLOCK) heterodimer binds to the E-box elements in the rupts the circadian cycle by uncoupling the central and peripheral
promoter regions of Per and Cry genes, thus activating their tran- clocks in the adipose tissue, and triggers leptin resistance leading to
scription proteins with feedback inhibition on the BMAL1/ development of obesity, an effect independent of other risk fac-
CLOCK. Six hours of sleep curtailment was sufficient to reduce
112
tors.117 In the large prospective Nurses’ Health Study 2, early chro-
BMAL1 binding to the E-box elements of Per gene.23 Other impor- notype combined with increasing years of rotating night shift work
tant regulators that integrate the effects of circadian clock on meta- aggravated diabetes risk, even after adjustment for patients’ attri-
bolic pathways include the clock-controlled genes and certain tran- butes, family history of diabetes, diet, physical activity and self-re-
scription factors e.g., REV-ERBα, retinoid-related orphan receptor ported sleep duration.118 Interestingly, late chronotype alone pre-
α, and peroxisome proliferator-activated receptor α.2,113 These genes dicted a 51% (hazard ratio, 1.51; 95% CI, 1.13–2.03) excess risk of
can also be categorized by type of regulations e.g., circadian cycle developing T2DM, which was attenuated by longer night shift ex-
only (BMAL1), sleep-wake cycle only (Homer1a) or both (Per). posure, presumably due to less interference to the “usual” circadian
Hence, the effects of sleep on gene expression, subsequent epigen- rhythm.118 These findings support the notion that chronotype-
etic modifications and metabolic perturbations require further adapted work schedules can possibly reduce the circadian misalign-
translational research to improve our understanding about the ment and prevent future cardiometabolic risk.
genes involved and the details of the regulation.23
The circadian clock has been demonstrated to regulate the diur-
Coordination of the sleep/wake cycle as well as the metabolic nal fluctuations of certain human metabolites such as the fatty acids
and fasting/feeding cycle are all essential to maintain a normal cir- and amino acids, independent of the fasting/feeding cycle.119 In the
cadian oscillatory system for healthy bodily functions. Glucose ho- first human metabolomics study conducted during a 48-hour
meostasis is regulated by both the central clock that synchronizes sleep/wake cycle, 27 of the 171 measured metabolites (e.g., fatty
sleep and feeding, and peripheral tissue clocks that coordinate one’s acids, tryptophan, taurine, and serotonin) were significantly elevat-
behavior with glucose synthesis and utilization. When BMAL1/
114
ed with sleep curtailment.120 This creates novel opportunities for
CLOCK heterodimer colocalizes with the pancreatic transcription potential therapeutic intervention targeting the key clock-regulated
factor pancreatic and duodenal homeobox 1 on the regulatory sites metabolic pathways and application of these noninvasive biomark-
of beta-cell cycling genes, pancreatic beta-cell maturation is en- ers for disease prediction and monitoring.
hanced with possible pulsatile insulin secretion according to the
circadian rhythmicity.114 Similarly, BMAL1-ablation in mice reduc- CONCLUSION
es insulin exocytosis from pancreatic beta-cell, resulting in hyper-
glycemia.23 Based on the genome-wide association studies, individ- Good sleep hygiene is crucial to maintain optimal functions of
uals with T2DM and melatonin receptor 1B (MTNR1B) risk allele the neuroendocrine and appetite regulation systems. To date, there

18 | http://www.jomes.org J Obes Metab Syndr 2018;27:4-24

Ding C, et al. Sleep and Obesity

is clear evidence in support of a causal relationship between sleep, 91-101.

circadian misalignment and cardiometabolic risk. Thus, health pro- 7. Liu Y, Wheaton AG, Chapman DP, Cunningham TJ, Lu H,
motion campaigns should look beyond conventional strategies by Croft JB. Prevalence of healthy sleep duration among adults:
emphasizing the pivotal role of improving sleep environment to United States, 2014. MMWR Morb Mortal Wkly Rep 2016;
curb the obesity epidemic. Nonetheless, there is a pressing need for 65:137-41.
future research to delineate the molecular intersections between 8. Cao XL, Wang SB, Zhong BL, Zhang L, Ungvari GS, Ng CH,
sleep, circadian clock and metabolic pathways, as well as to explore et al. The prevalence of insomnia in the general population
potential preventive and therapeutic approaches to optimize sleep in China: a meta-analysis. PLoS One 2017;12:e0170772.
and circadian rhythm in predisposed individuals. 9. Bin YS, Marshall NS, Glozier N. Sleeping at the limits: the
changing prevalence of short and long sleep durations in 10
CONFLICTS OF INTEREST countries. Am J Epidemiol 2013;177:826-33.
10. Jike M, Itani O, Watanabe N, Buysse DJ, Kaneita Y. Long
The authors declare no conflict of interest. sleep duration and health outcomes: a systematic review,
meta-analysis and meta-regression. Sleep Med Rev 2017 Jul
REFERENCES 5 [Epub]. https://doi.org/10.1016/j.smrv.2017.06.011
11. Ayas NT, White DP, Al-Delaimy WK, Manson JE, Stampfer
1. GBD 2015 Obesity Collaborators, Afshin A, Forouzanfar MH, MJ, Speizer FE, et al. A prospective study of self-reported
Reitsma MB, Sur P, Estep K, et al. Health effects of overweight sleep duration and incident diabetes in women. Diabetes Care
and obesity in 195 countries over 25 years. N Engl J Med 2017; 2003;26:380-4.
377:13-27. 12. Heymsfield SB, Wadden TA. Mechanisms, pathophysiology,
2. McHill AW, Wright KP Jr. Role of sleep and circadian dis- and management of obesity. N Engl J Med 2017;376:254-
ruption on energy expenditure and in metabolic predisposi- 66.
tion to human obesity and metabolic disease. Obes Rev 2017; 13. Nakazato M, Murakami N, Date Y, Kojima M, Matsuo H,
18 Suppl 1:15-24. Kangawa K, et al. A role for ghrelin in the central regulation
3. Iglowstein I, Jenni OG, Molinari L, Largo RH. Sleep dura- of feeding. Nature 2001;409:194-8.
tion from infancy to adolescence: reference values and gen- 14. Zigman JM, Elmquist JK. Minireview: from anorexia to obe-
erational trends. Pediatrics 2003;111:302-7. sity. The yin and yang of body weight control. Endocrinolo-
4. Consensus Conference Panel, Watson NF, Badr MS, Belenky gy 2003;144:3749-56.
G, Bliwise DL, Buxton OM, et al. Joint consensus statement 15. Dashti HS, Scheer FA, Jacques PF, Lamon-Fava S, Ordovás
of the American Academy of Sleep Medicine and Sleep Re- JM. Short sleep duration and dietary intake: epidemiologic
search Society on the recommended amount of sleep for a evidence, mechanisms, and health implications. Adv Nutr
healthy adult: methodology and discussion. Sleep 2015;38: 2015;6:648-59.
1161-83. 16. Colles SL, Dixon JB, O’Brien PE. Night eating syndrome
5. Paruthi S, Brooks LJ, D’Ambrosio C, Hall WA, Kotagal S, and nocturnal snacking: association with obesity, binge eat-
Lloyd RM, et al. Recommended amount of sleep for pediat- ing and psychological distress. Int J Obes (Lond) 2007;31:
ric populations: a consensus statement of the American Acad- 1722-30.
emy of Sleep Medicine. J Clin Sleep Med 2016;12:785-6. 17. Kant AK, Graubard BI. Association of self-reported sleep
6. Lee SW, Ng KY, Chin WK. The impact of sleep amount and duration with eating behaviors of American adults: NHANES
sleep quality on glycemic control in type 2 diabetes: a sys- 2005-2010. Am J Clin Nutr 2014;100:938-47.
tematic review and meta-analysis. Sleep Med Rev 2017;31: 18. Ding M, Keiley MK, Garza KB, Duffy PA, Zizza CA. Food

J Obes Metab Syndr 2018;27:4-24 http://www.jomes.org | 19

Ding C, et al. Sleep and Obesity

insecurity is associated with poor sleep outcomes among US 29. Baron KG, Reid KJ, Kern AS, Zee PC. Role of sleep timing
adults. J Nutr 2015;145:615-21. in caloric intake and BMI. Obesity (Silver Spring) 2011;19:
19. St-Onge MP, Roberts AL, Chen J, Kelleman M, O’Keeffe M, 1374-81.
RoyChoudhury A, et al. Short sleep duration increases en- 30. Stern JH, Grant AS, Thomson CA, Tinker L, Hale L, Bren-
ergy intakes but does not change energy expenditure in nor- nan KM, et al. Short sleep duration is associated with de-
mal-weight individuals. Am J Clin Nutr 2011;94:410-6. creased serum leptin, increased energy intake and decreased
20. Nedeltcheva AV, Kilkus JM, Imperial J, Kasza K, Schoeller diet quality in postmenopausal women. Obesity (Silver Spring)
DA, Penev PD. Sleep curtailment is accompanied by in- 2014;22:E55-61.
creased intake of calories from snacks. Am J Clin Nutr 2009; 31. Motivala SJ, Tomiyama AJ, Ziegler M, Khandrika S, Irwin
89:126-33. MR. Nocturnal levels of ghrelin and leptin and sleep in chron-
21. Shi Z, McEvoy M, Luu J, Attia J. Dietary fat and sleep dura- ic insomnia. Psychoneuroendocrinology 2009;34:540-5.
tion in Chinese men and women. Int J Obes (Lond) 2008; 32. Spiegel K, Leproult R, Colecchia EF, L’Hermite-Balériaux M,
32:1835-40. Nie Z, Copinschi G, et al. Adaptation of the 24-h growth
22. Dashti HS, Follis JL, Smith CE, Tanaka T, Cade BE, Gottli- hormone profile to a state of sleep debt. Am J Physiol Regul
eb DJ, et al. Habitual sleep duration is associated with BMI Integr Comp Physiol 2000;279:R874-83.
and macronutrient intake and may be modified by CLOCK 33. Van Cauter E, Plat L, Copinschi G. Interrelations between
genetic variants. Am J Clin Nutr 2015;101:135-43. sleep and the somatotropic axis. Sleep 1998;21:553-66.
23. Arble DM, Bass J, Behn CD, Butler MP, Challet E, Czeisler 34. Sandhu MS, Heald AH, Gibson JM, Cruickshank JK, Dung-
C, et al. Impact of sleep and circadian disruption on energy er DB, Wareham NJ. Circulating concentrations of insulin-
balance and diabetes: a summary of workshop discussions. like growth factor-I and development of glucose intolerance:
Sleep 2015;38:1849-60. a prospective observational study. Lancet 2002;359:1740-5.
24. Taheri S, Lin L, Austin D, Young T, Mignot E. Short sleep 35. Juul A, Scheike T, Davidsen M, Gyllenborg J, Jørgensen T.
duration is associated with reduced leptin, elevated ghrelin, Low serum insulin-like growth factor I is associated with in-
and increased body mass index. PLoS Med 2004;1:e62. creased risk of ischemic heart disease: a population-based
25. Spiegel K, Leproult R, L’hermite-Balériaux M, Copinschi G, case-control study. Circulation 2002;106:939-44.
Penev PD, Van Cauter E. Leptin levels are dependent on 36. Sukhanov S, Higashi Y, Shai SY, Vaughn C, Mohler J, Li Y, et
sleep duration: relationships with sympathovagal balance, al. IGF-1 reduces inflammatory responses, suppresses oxida-
carbohydrate regulation, cortisol, and thyrotropin. J Clin En- tive stress, and decreases atherosclerosis progression in ApoE-
docrinol Metab 2004;89:5762-71. deficient mice. Arterioscler Thromb Vasc Biol 2007;27:2684-
26. Greer SM, Goldstein AN, Walker MP. The impact of sleep 90.
deprivation on food desire in the human brain. Nat Com- 37. García-García F, Juárez-Aguilar E, Santiago-García J, Cardi-
mun 2013;4:2259. nali DP. Ghrelin and its interactions with growth hormone,
27. St-Onge MP, Wolfe S, Sy M, Shechter A, Hirsch J. Sleep re- leptin and orexins: implications for the sleep-wake cycle and
striction increases the neuronal response to unhealthy food metabolism. Sleep Med Rev 2014;18:89-97.
in normal-weight individuals. Int J Obes (Lond) 2014;38: 38. Gram IT, Norat T, Rinaldi S, Dossus L, Lukanova A, Téhard
411-6. B, et al. Body mass index, waist circumference and waist-hip
28. Benedict C, Brooks SJ, O’Daly OG, Almèn MS, Morell A, ratio and serum levels of IGF-I and IGFBP-3 in European
Åberg K, et al. Acute sleep deprivation enhances the brain’s women. Int J Obes (Lond) 2006;30:1623-31.
response to hedonic food stimuli: an fMRI study. J Clin En- 39. Yeap BB, Chubb SA, Ho KK, Setoh JW, McCaul KA, Nor-
docrinol Metab 2012;97:E443-7. man PE, et al. IGF1 and its binding proteins 3 and 1 are dif-

20 | http://www.jomes.org J Obes Metab Syndr 2018;27:4-24

Ding C, et al. Sleep and Obesity

ferentially associated with metabolic syndrome in older men. A community-based study on the association between in-
Eur J Endocrinol 2010;162:249-57. somnia and hypothalamic-pituitary-adrenal axis: sex and pu-
40. Spiegel K, Leproult R, Van Cauter E. Impact of sleep debt bertal influences. J Clin Endocrinol Metab 2014;99:2277-87.
on metabolic and endocrine function. Lancet 1999;354: 51. Irwin M, Thompson J, Miller C, Gillin JC, Ziegler M. Ef-
1435-9. fects of sleep and sleep deprivation on catecholamine and
41. Fries E, Dettenborn L, Kirschbaum C. The cortisol awaken- interleukin-2 levels in humans: clinical implications. J Clin
ing response (CAR): facts and future directions. Int J Psy- Endocrinol Metab 1999;84:1979-85.
chophysiol 2009;72:67-73. 52. Lusardi P, Zoppi A, Preti P, Pesce RM, Piazza E, Fogari R.
42. Kumari M, Badrick E, Ferrie J, Perski A, Marmot M, Chan- Effects of insufficient sleep on blood pressure in hyperten-
dola T. Self-reported sleep duration and sleep disturbance sive patients: a 24-h study. Am J Hypertens 1999;12(1 Pt
are independently associated with cortisol secretion in the 1):63-8.
Whitehall II study. J Clin Endocrinol Metab 2009;94:4801-9. 53. Broussard JL, Ehrmann DA, Van Cauter E, Tasali E, Brady
43. Huang T, Poole EM, Vetter C, Rexrode KM, Kubzansky LD, MJ. Impaired insulin signaling in human adipocytes after ex-
Schernhammer E, et al. Habitual sleep quality and diurnal perimental sleep restriction: a randomized, crossover study.
rhythms of salivary cortisol and dehydroepiandrosterone in Ann Intern Med 2012;157:549-57.
postmenopausal women. Psychoneuroendocrinology 2017; 54. Kong AP, Wing YK, Choi KC, Li AM, Ko GT, Ma RC, et al.
84:172-80. Associations of sleep duration with obesity and serum lipid
44. Zhang J, Ma RC, Kong AP, So WY, Li AM, Lam SP, et al. profile in children and adolescents. Sleep Med 2011;12:659-
Relationship of sleep quantity and quality with 24-hour uri- 65.
nary catecholamines and salivary awakening cortisol in healthy 55. Zhan Y, Chen R, Yu J. Sleep duration and abnormal serum
middle-aged adults. Sleep 2011;34:225-33. lipids: the China Health and Nutrition Survey. Sleep Med
45. Lemola S, Perkinson-Gloor N, Hagmann-von Arx P, Brand S, 2014;15:833-9.
Holsboer-Trachsler E, Grob A, et al. Morning cortisol secre- 56. Patel SR, Malhotra A, White DP, Gottlieb DJ, Hu FB. Asso-
tion in school-age children is related to the sleep pattern of ciation between reduced sleep and weight gain in women.
the preceding night. Psychoneuroendocrinology 2015;52: Am J Epidemiol 2006;164:947-54.
297-301. 57. Chaput JP, Després JP, Bouchard C, Tremblay A. The asso-
46. Räikkönen K, Matthews KA, Pesonen AK, Pyhälä R, Paa- ciation between sleep duration and weight gain in adults: a
vonen EJ, Feldt K, et al. Poor sleep and altered hypothalam- 6-year prospective study from the Quebec Family Study.
ic-pituitary-adrenocortical and sympatho-adrenal-medullary Sleep 2008;31:517-23.
system activity in children. J Clin Endocrinol Metab 2010; 58. López-García E, Faubel R, León-Muñoz L, Zuluaga MC,
95:2254-61. Banegas JR, Rodríguez-Artalejo F. Sleep duration, general
47. Rao MN, Blackwell T, Redline S, Punjabi NM, Barrett-Con- and abdominal obesity, and weight change among the older
nor E, Neylan TC, et al. Association between sleep duration adult population of Spain. Am J Clin Nutr 2008;87:310-6.
and 24-hour urine free cortisol in the MrOS Sleep Study. 59. Stranges S, Cappuccio FP, Kandala NB, Miller MA, Taggart
PLoS One 2013;8:e75205. FM, Kumari M, et al. Cross-sectional versus prospective as-
48. Richardson GS. Human physiological models of insomnia. sociations of sleep duration with changes in relative weight
Sleep Med 2007;8 Suppl 4:S9-14. and body fat distribution: the Whitehall II Study. Am J Epi-
49. Bonnet MH, Arand DL. Hyperarousal and insomnia: state demiol 2008;167:321-9.
of the science. Sleep Med Rev 2010;14:9-15. 60. Nishiura C, Noguchi J, Hashimoto H. Dietary patterns only
50. Zhang J, Lam SP, Li SX, Ma RC, Kong AP, Chan MH, et al. partially explain the effect of short sleep duration on the in-

J Obes Metab Syndr 2018;27:4-24 http://www.jomes.org | 21

Ding C, et al. Sleep and Obesity

cidence of obesity. Sleep 2010;33:753-7. time sleep duration and the incidence of obesity and type 2
61. Watanabe M, Kikuchi H, Tanaka K, Takahashi M. Associa- diabetes: findings from the prospective Pizarra study. Sleep
tion of short sleep duration with weight gain and obesity at Med 2014;15:1398-404.
1-year follow-up: a large-scale prospective study. Sleep 2010; 72. Kim JY, Yadav D, Ahn SV, Koh SB, Park JT, Yoon J, et al. A
33:161-7. prospective study of total sleep duration and incident meta-
62. Itani O, Kaneita Y, Murata A, Yokoyama E, Ohida T. Associ- bolic syndrome: the ARIRANG study. Sleep Med 2015;16:
ation of onset of obesity with sleep duration and shift work 1511-5.
among Japanese adults. Sleep Med 2011;12:341-5. 73. Zhang B, Hao Y, Zhou J, Jia F, Li X, Tang Y, et al. The asso-
63. Lyytikäinen P, Rahkonen O, Lahelma E, Lallukka T. Associ- ciation between sleep patterns and overweight/obesity in
ation of sleep duration with weight and weight gain: a pro- Chinese children: a cross-sectional study. Neuropsychiatr
spective follow-up study. J Sleep Res 2011;20:298-302. Dis Treat 2015;11:2209-16.
64. Kobayashi D, Takahashi O, Deshpande GA, Shimbo T, Fu- 74. Mallon L, Broman JE, Hetta J. High incidence of diabetes in
kui T. Association between weight gain, obesity, and sleep men with sleep complaints or short sleep duration: a 12-year
duration: a large-scale 3-year cohort study. Sleep Breath follow-up study of a middle-aged population. Diabetes Care
2012;16:829-33. 2005;28:2762-7.
65. Yiengprugsawan V, Banwell C, Seubsman SA, Sleigh AC; 75. Yaggi HK, Araujo AB, McKinlay JB. Sleep duration as a risk
Thai Cohort Study Team. Short sleep and obesity in a large factor for the development of type 2 diabetes. Diabetes Care
national cohort of Thai adults. BMJ Open 2012;2:e000561. 2006;29:657-61.
66. Nagai M, Tomata Y, Watanabe T, Kakizaki M, Tsuji I. Asso- 76. Gangwisch JE, Heymsfield SB, Boden-Albala B, Buijs RM,
ciation between sleep duration, weight gain, and obesity for Kreier F, Pickering TG, et al. Sleep duration as a risk factor
long period. Sleep Med 2013;14:206-10. for diabetes incidence in a large U.S. sample. Sleep 2007;30:
67. Ohkuma T, Fujii H, Iwase M, Kikuchi Y, Ogata S, Idewaki Y, 1667-73.
et al. Impact of sleep duration on obesity and the glycemic 77. Hayashino Y, Fukuhara S, Suzukamo Y, Okamura T, Tanaka
level in patients with type 2 diabetes: the Fukuoka Diabetes T, Ueshima H, et al. Relation between sleep quality and
Registry. Diabetes Care 2013;36:611-7. quantity, quality of life, and risk of developing diabetes in
68. Sayón-Orea C, Bes-Rastrollo M, Carlos S, Beunza JJ, Baster- healthy workers in Japan: the High-risk and Population
ra-Gortari FJ, Martínez-González MA. Association between Strategy for Occupational Health Promotion (HIPOP-OHP)
sleeping hours and siesta and the risk of obesity: the SUN Study. BMC Public Health 2007;7:129.
Mediterranean Cohort. Obes Facts 2013;6:337-47. 78. Beihl DA, Liese AD, Haffner SM. Sleep duration as a risk
69. Xiao Q, Arem H, Moore SC, Hollenbeck AR, Matthews CE. factor for incident type 2 diabetes in a multiethnic cohort.
A large prospective investigation of sleep duration, weight Ann Epidemiol 2009;19:351-7.
change, and obesity in the NIH-AARP Diet and Health Study 79. Chaput JP, Després JP, Bouchard C, Astrup A, Tremblay A.
cohort. Am J Epidemiol 2013;178:1600-10. Sleep duration as a risk factor for the development of type 2
70. Vgontzas AN, Fernandez-Mendoza J, Miksiewicz T, Kritikou diabetes or impaired glucose tolerance: analyses of the Que-
I, Shaffer ML, Liao D, et al. Unveiling the longitudinal asso- bec Family Study. Sleep Med 2009;10:919-24.
ciation between short sleep duration and the incidence of 80. Xu Q, Song Y, Hollenbeck A, Blair A, Schatzkin A, Chen H.
obesity: the Penn State Cohort. Int J Obes (Lond) 2014;38: Day napping and short night sleeping are associated with
825-32. higher risk of diabetes in older adults. Diabetes Care 2010;
71. Gutiérrez-Repiso C, Soriguer F, Rubio-Martín E, Esteva de 33:78-83.
Antonio I, Ruiz de Adana MS, Almaraz MC, et al. Night- 81. Kita T, Yoshioka E, Satoh H, Saijo Y, Kawaharada M, Okada

22 | http://www.jomes.org J Obes Metab Syndr 2018;27:4-24

Ding C, et al. Sleep and Obesity

E, et al. Short sleep duration and poor sleep quality increase 91. Lyytikäinen P, Lallukka T, Lahelma E, Rahkonen O. Sleep
the risk of diabetes in Japanese workers with no family his- problems and major weight gain: a follow-up study. Int J
tory of diabetes. Diabetes Care 2012;35:313-8. Obes (Lond) 2011;35:109-14.
82. von Ruesten A, Weikert C, Fietze I, Boeing H. Association 92. Huang L, Zhou J, Sun Y, Li Z, Lei F, Zhou G, et al. Poly-
of sleep duration with chronic diseases in the European Pro- somnographically determined sleep and body mass index in
spective Investigation into Cancer and Nutrition (EPIC)- patients with insomnia. Psychiatry Res 2013;209:540-4.
Potsdam study. PLoS One 2012;7:e30972. 93. Piccolo RS, Yang M, Bliwise DL, Yaggi HK, Araujo AB. Ra-
83. Holliday EG, Magee CA, Kritharides L, Banks E, Attia J. cial and socioeconomic disparities in sleep and chronic dis-
Short sleep duration is associated with risk of future diabetes ease: results of a longitudinal investigation. Ethn Dis 2013;
but not cardiovascular disease: a prospective study and me- 23:499-507.
ta-analysis. PLoS One 2013;8:e82305. 94. Sivertsen B, Lallukka T, Salo P, Pallesen S, Hysing M, Kroks-
84. Heianza Y, Kato K, Fujihara K, Tanaka S, Kodama S, Hanyu tad S, et al. Insomnia as a risk factor for ill health: results
O, et al. Role of sleep duration as a risk factor for type 2 dia- from the large population-based prospective HUNT Study
betes among adults of different ages in Japan: the Niigata in Norway. J Sleep Res 2014;23:124-32.
Wellness Study. Diabet Med 2014;31:1363-7. 95. Tan X, Alén M, Cheng SM, Mikkola TM, Tenhunen J, Lyy-
85. Lou P, Zhang P, Zhang L, Chen P, Chang G, Zhang N, et al. tikäinen A, et al. Associations of disordered sleep with body
Effects of sleep duration and sleep quality on prevalence of fat distribution, physical activity and diet among overweight
type 2 diabetes mellitus: a 5-year follow-up study in China. middle-aged men. J Sleep Res 2015;24:414-24.
Diabetes Res Clin Pract 2015;109:178-84. 96. Nilsson PM, Rööst M, Engström G, Hedblad B, Berglund G.
86. Han X, Liu B, Wang J, Pan A, Li Y, Hu H, et al. Long sleep Incidence of diabetes in middle-aged men is related to sleep
duration and afternoon napping are associated with higher disturbances. Diabetes Care 2004;27:2464-9.
risk of incident diabetes in middle-aged and older Chinese: 97. Björkelund C, Bondyr-Carlsson D, Lapidus L, Lissner L,
the Dongfeng-Tongji cohort study. Ann Med 2016;48:216- Månsson J, Skoog I, et al. Sleep disturbances in midlife unre-
23. lated to 32-year diabetes incidence: the prospective popula-
87. Knutson KL, Ryden AM, Mander BA, Van Cauter E. Role tion study of women in Gothenburg. Diabetes Care 2005;
of sleep duration and quality in the risk and severity of type 28:2739-44.
2 diabetes mellitus. Arch Intern Med 2006;166:1768-74. 98. Meisinger C, Heier M, Loewel H; MONICA/KORA Augs-
88. Kim BK, Kim BS, An SY, Lee MS, Choi YJ, Han SJ, et al. burg Cohort Study. Sleep disturbance as a predictor of type
Sleep duration and glycemic control in patients with diabe- 2 diabetes mellitus in men and women from the general
tes mellitus: Korea National Health and Nutrition Examina- population. Diabetologia 2005;48:235-41.
tion Survey 2007-2010. J Korean Med Sci 2013;28:1334-9. 99. Lee JA, Sunwoo S, Kim YS, Yu BY, Park HK, Jeon TH, et al.
89. Wang T, Lu J, Wang W, Mu Y, Zhao J, Liu C, et al. Sleep du- The effect of sleep quality on the development of type 2 di-
ration and snoring associate with hypertension and glycae- abetes in primary care patients. J Korean Med Sci 2016;31:
mic control in patients with diabetes. Diabet Med 2015;32: 240-6.
1001-7. 100. Wan Mahmood WA, Draman Yusoff MS, Behan LA, Di
90. Kong AP, Choi KC, Zhang J, Luk A, Lam SP, Chan MH, et Perna A, Kyaw Tun T, McDermott J, et al. Association be-
al. Curvilinear associations of sleep patterns during week- tween sleep disruption and levels of lipids in Caucasians
days and weekends with glycemic control in type 2 diabetes: with type 2 diabetes. Int J Endocrinol 2013;2013:341506.
the Hong Kong Diabetes Registry. Acta Diabetol 2017;54: 101. Cho EH, Lee H, Ryu OH, Choi MG, Kim SW. Sleep distur-
151-62. bances and glucoregulation in patients with type 2 diabetes.

J Obes Metab Syndr 2018;27:4-24 http://www.jomes.org | 23

Ding C, et al. Sleep and Obesity

J Korean Med Sci 2014;29:243-7. disturbances in sleep disorders. Endocrinol Metab Clin
102. Nefs G, Donga E, van Someren E, Bot M, Speight J, Pouwer North Am 2002;31:15-36.
F. Subjective sleep impairment in adults with type 1 or type 111. Mullington JM, Haack M, Toth M, Serrador JM, Meier-Ew-
2 diabetes: results from diabetes MILES-The Netherlands. ert HK. Cardiovascular, inflammatory, and metabolic conse-
Diabetes Res Clin Pract 2015;109:466-75. quences of sleep deprivation. Prog Cardiovasc Dis 2009;51:
103. Osonoi Y, Mita T, Osonoi T, Saito M, Tamasawa A, Nakaya- 294-302.
ma S, et al. Poor sleep quality is associated with increased 112. Partch CL, Green CB, Takahashi JS. Molecular architecture
arterial stiffness in Japanese patients with type 2 diabetes of the mammalian circadian clock. Trends Cell Biol 2014;
mellitus. BMC Endocr Disord 2015;15:29. 24:90-9.
104. American Academy of Sleep Medicine. International classifi- 113. Albrecht U. The circadian clock, metabolism and obesity.
cation of sleep disorders. Darien (IL): American Academy Obes Rev 2017;18 Suppl 1:25-33.
of Sleep Medicine; 2014. 114. Perelis M, Marcheva B, Ramsey KM, Schipma MJ, Hutchi-
105. Watson NF, Goldberg J, Arguelles L, Buchwald D. Genetic son AL, Taguchi A, et al. Pancreatic β cell enhancers regulate
and environmental influences on insomnia, daytime sleepi- rhythmic transcription of genes controlling insulin secretion.
ness, and obesity in twins. Sleep 2006;29:645-9. Science 2015;350:aac4250.
106. Cappuccio FP, D’Elia L, Strazzullo P, Miller MA. Quantity 115. Leproult R, Holmbäck U, Van Cauter E. Circadian misalign-
and quality of sleep and incidence of type 2 diabetes: a sys- ment augments markers of insulin resistance and inflamma-
tematic review and meta-analysis. Diabetes Care 2010;33: tion, independently of sleep loss. Diabetes 2014;63:1860-9.
414-20. 116. Buxton OM, Cain SW, O’Connor SP, Porter JH, Duffy JF,
107. Anothaisintawee T, Reutrakul S, Van Cauter E, Thakkinstian Wang W, et al. Adverse metabolic consequences in humans
A. Sleep disturbances compared to traditional risk factors for of prolonged sleep restriction combined with circadian dis-
diabetes development: systematic review and meta-analysis. ruption. Sci Transl Med 2012;4:129ra43.
Sleep Med Rev 2016;30:11-24. 117. Kettner NM, Mayo SA, Hua J, Lee C, Moore DD, Fu L. Cir-
108. Vgontzas AN, Liao D, Pejovic S, Calhoun S, Karataraki M, cadian dysfunction induces leptin resistance in mice. Cell
Bixler EO. Insomnia with objective short sleep duration is Metab 2015;22:448-59.
associated with type 2 diabetes: a population-based study. 118. Vetter C, Devore EE, Ramin CA, Speizer FE, Willett WC,
Diabetes Care 2009;32:1980-5. Schernhammer ES. Mismatch of sleep and work timing and
109. Johann AF, Hertenstein E, Kyle SD, Baglioni C, Feige B, Nis- risk of type 2 diabetes. Diabetes Care 2015;38:1707-13.
sen C, et al. Insomnia with objective short sleep duration is 119. Dallmann R, Viola AU, Tarokh L, Cajochen C, Brown SA.
associated with longer duration of insomnia in the Freiburg The human circadian metabolome. Proc Natl Acad Sci U S
Insomnia Cohort compared to insomnia with normal sleep A 2012;109:2625-9.
duration, but not with hypertension. PLoS One 2017;12: 120. Davies SK, Ang JE, Revell VL, Holmes B, Mann A, Robert-
e0180339. son FP, et al. Effect of sleep deprivation on the human me-
110. Vgontzas AN, Chrousos GP. Sleep, the hypothalamic-pitu- tabolome. Proc Natl Acad Sci U S A 2014;111:10761-6.
itary-adrenal axis, and cytokines: multiple interactions and

24 | http://www.jomes.org J Obes Metab Syndr 2018;27:4-24