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The online version of this article can be found at:
2010 12: 47 originally published online 7 May 2010 Biol Res Nurs
Norah S. Simpson, Siobhan Banks and David F. Dinges
Sleep Restriction Is Associated With Increased Morning Plasma Leptin Concentrations, Especially in
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Sleep Restriction Is Associated With
Increased Morning Plasma Leptin
Concentrations, Especially in Women
Norah S. Simpson, PhD,1Siobhan Banks, PhD,2and
David F. Dinges, PhD3
Study Objectives: We evaluated the effects of sleep restriction on leptin levels in a large, diverse sample of healthy participants,
while allowing free access to food. Methods: Prospective experimental design. After 2 nights of baseline sleep, 136 participants
(49% women, 56% African Americans) received 5 consecutive nights of 4 hours time in bed (TIB). Additionally, one subset of
participants received 2 additional nights of either further sleep restriction (n ¼ 27) or increased sleep opportunity (n ¼ 37).
Control participants (n ¼ 9) received 10 hr TIB on all study nights. Plasma leptin was measured between 10:30 a.m. and 12:00
noon following baseline sleep, after the initial sleep-restriction period, and after 2 nights of further sleep restriction or recovery
sleep. Results: Leptin levels increased significantly among sleep-restricted participants after 5 nights of 4 hr TIB (Z ¼ ?8.43,
p < .001). Increases were significantly greater among women compared to men (Z ¼ ?4.77, p < .001) and among participants
with higher body mass index (BMI) compared to those with lower (Z ¼ ?2.09, p ¼ .036), though participants in all categories
(sex, race/ethnicity, BMI, and age) demonstrated significant increases. There was also a significant effect of allowed TIB on leptin
levels following the 2 additional nights of sleep restriction (p < .001). Participants in the control condition showed no significant
changes in leptin levels. Conclusions: These findings suggest that sleep restriction with ad libitum access to food significantly
increases morning plasma leptin levels, particularly among women.
leptin, sleep restriction, sex, obesity
Leptin is an adipocyte-derived, proinflammatory hormone that
plays a key role in energy homeostasis (Lago, Gomez, Lago,
and decreased food intake (Collins et al., 1996). Circulating
leptin levels are correlated with adipose tissue mass, and levels
are higher in obese compared to lean adults (Considine et al.,
1996). Epidemiologic evidence suggests that in recent years,
rates of obesity/overweight have increased (Flegal, Carroll,
Ogden, & Johnson, 2002; Schiller, Martinez, & Barnes, 2006),
while self-reported sleep durations have decreased (National
Sleep Foundation, 1998, 2006; Tune, 1968). Numerous studies
have also documented a strong relationship between shorter
habitual sleep durations and higher body mass indices (BMIs)
in both adults and children (for meta-analytic review, see
Cappuccio et al., 2008). Although some recent evidence
suggests that other characteristics of sleep (e.g., snoring, sleep
fragmentation) may contribute to the relationship between
shorter sleep duration and higher BMI (Lauderdale et al., 2009),
the underlying biological mechanisms are not yet understood.
link between increasing rates of obesity and decreasing
habitual sleep durations. Two epidemiological studies have
reported that shorter self-reported sleep durations are associated
with decreased fasting plasma leptin levels and higher BMIs
(Chaput, Despres, Bouchard, & Tremblay, 2007; Taheri, Lin,
Austin, Young, & Mignot, 2004). Additionally, a number of
experimental studies have reported decreases in leptin following
sleep restriction (Gomez-Merino, Chennaoui, Drogou, Bonneau,
& Guezennec, 2002; Gomez-Merino et al., 2005; Guilleminault
et al., 2003; Gundersen, Opstad, Reistad, Thrane, & Vaagenes,
2006; Mullington et al., 2003; Nindl et al., 2006; Spiegel,
1Department of Neurology, Beth Israel Deaconess Medical Center, Harvard
Medical School, Boston, MA, USA
2Centre for Sleep Research, University of South Australia, Adelaide, South
3Unit for Experimental Psychiatry, Department of Psychiatry, University of
Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
Norah S. Simpson, Department of Neurology, Beth Israel Deaconess Medical
Center, Harvard Medical School, 330 Longwood Ave., Boston, MA 02215, USA
Biological Research for Nursing
ª The Author(s) 2010
Reprints and permission:
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Leproult, et al., 2004; Spiegel, Tasali, Penev, & Van Cauter,
lowing sleep restriction (Nedeltcheva et al., 2009; Schmid,
ofthese studieshavereliedonsmallsamples(N? 12)composed
primarily ofmales, and all but one either severely restricted/con-
trolled food intake or allowed daily caloric intake to vary during
sleep restriction but assessed leptin levels during a subsequent
provided during sleep restriction, leptin levels increased signifi-
cantly across the sleep restriction period (Shea, Hilton, Orlova,
Ayers, & Mantzoros, 2005). Thus, there are very limited data
available on the effects of sleep restriction on leptin levels when
other physiologic systems related to leptin levels and mainte-
nance of energy balance (i.e., food intake and physical activity)
are permitted to vary in response to the changing physiologic
Additionally, no previous studies have enrolled a suffi-
ciently large sample to examine the effects of demographic
characteristics on the effects of sleep restriction. Women, in
particular, have been understudied. Given that health risks vary
according to sex and race/ethnicity (see, e.g., Ervin, 2009;
Lloyd-Jones et al., 2009), evaluation of these phenomena
across a diverse population is critical. To address these issues,
we conducted a study to investigate the effects of sustained
sleep restriction on leptin levels while allowing participants
free access to food in addition to regularly scheduled meals.
The amount of sleep restriction was held constant for the first
5 days and then varied systematically in a subset of participants
for 2 additional nights to assess the effects of duration of sleep
opportunity on plasma leptin levels. We also used a larger sam-
ple size than has previously been studied, enrolling both men
and women of diverse racial/ethnic backgrounds.
area newspapers and were compensated for participation with
payments based on time of participation in study (e.g.,
screening only, complete participation). The initial pool of
participants comprised 163 healthy adults who provided
informed consent to take part in this study, which was
approved by the institutional review board (IRB) of the
University of Pennsylvania. Participants underwent a complete
medical history and physical screening to rule out hepatitis,
cancer, other serious medical conditions, and Axis I psychiatric
disorders (e.g., major depressive disorder, schizophrenia).
Current use of prescribed medications was also an exclusion
General Clinical Research Center at the University of Pennsyl-
vania; height and weight measurements for BMI were also
collected by study nurses at this time. For female participants,
the start date of last menstrual period was also collected via
self-report to assess menstrual phase. Clinical chemistry and
urine tests were performed to ensure participants were free of
active infection and illicit drugs. Normal sleep–wake rhythms
ing wake time between 06:00 and 09:00 hr) were verified by
sleep logs and actigraphy for a period of at least 1 week prior
toparticipation inthe study. Thelatter criterionfunctioned both
to exclude potential participants with a circadian phase disorder
and to ensure that the assigned wake times in the study did not
deviate significantly from participants’ normal sleep cycles.
Complete data were collected from 145 participants (mean
age 30.42 years, range 22–45 years; mean BMI 24.66 kg/m2,
range 17.7–32.6 kg/m2; sex: 49% women; race/ethnicity:
ticipants (11% of total) who had incomplete data (13 withdrew
or were withdrawn for minor physical or performance con-
cerns; 2 had one or more data points below the lowest leptin
level that could be reliably detected by assay reagents [verified
with standardized samples]; 1 had an insufficient sample to
assay at one data point; 1 had one unsuccessful blood draw;
1 had baseline leptin data >2 SD above the mean) did not differ
significantly from completers on any demographic variable
(p values > .42; race/ethnicity comparison based on Caucasian
and African American participants only). Data from partici-
pants with incomplete data are not presented.
Sleep restriction. An 11-day protocol was conducted in the
Sleep and Chronobiology Laboratory at the Hospital of the
University of Pennsylvania. Participants were kept in constant
dim ambient light of <50 lux for the duration of the study and
were not permitted visitors. Lights were maintained at this low
level to prevent any changes in the time-keeping hormone mel-
atonin, which is sensitive to light levels.
Participants were randomized to either the sleep restriction
(n ¼ 136) or the control condition (n ¼ 9) based on power cal-
culations generated for the main (neurobehavioral) outcome
measure of the study. Sleep-restricted participants did not dif-
fer significantly from control participants on any demographic
measure (p values > .14). The 136 sleep-restricted participants
completed 2 nights of baseline sleep (B1 and B2; 10 hr time in
bed [TIB]/night) followed by 5 nights of sleep restriction
(SR1–SR5; 4 hr TIB/night). Of these participants, 27 were
randomized to receive 2 additional nights of further sleep
restriction (FR group: FR1 and FR2: 0, 2, or 4 hr TIB/night)
and 37 were randomized to receive 2 nights of increased sleep
time (recovery sleep group: RS1 and RS2: 6, 8, or 10 hr TIB/
night). Sleep and wake times were anchored to a morning wake
time of 08:00 hr; as such, on nights with a 4-hr sleep
opportunity, participants were allowed in bed only during
04:00–08:00 hr. All sleep-restricted participants received
2 additional nights of 10 hr and 12 hr TIB before leaving the
laboratory (data not presented). A cohort of 9 control partici-
pants received 10 hr TIB/night for the duration of the 11-
night protocol. All participants were run through the protocol
in groups of 4–5, which helped to buffer feelings of isolation
in the laboratory environment through social interaction. See
48Biological Research for Nursing 12(1)
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Figure 1 for a more detailed description of the study design and
Blood-sampling paradigm. Blood draws were performed
through the antecubital vein between 10:30 and 12:00 on the
mornings following B2, SR5, and FR2 or RS2. Samples were
collected from control participants on equivalent study proto-
col days. Samples were drawn into 10-mL plastic vacutainer
tubes spray-coated withsodium
aliquotted, and frozen at ?80?C until analysis. Samples were
assayed for leptin and a subset of other inflammatory and endo-
crine markers. Only leptin results are presented here; analysis
of other data is currently in progress.
Leptin assays. Plasma leptin levels were measured by a com-
mercially available radioimmunoassay kit (Millipore, Billerica,
Massachusetts). The sensitivity limit was 0.5 ng/mL, interassay
coefficients of variation were 14.4% and 9.2% (for low and
high leptin concentrations, respectively), and intraassay coeffi-
cients of variation were 5.6% and 3.4% (for low and high
concentration leptin standards, respectively). All samples and
standards were assayed in duplicate within the same assay kit.
Laboratory environment. Participants received three meals per
day plus an optional evening snack on nights when they
received sleep opportunities of less than 8 hr TIB. Study parti-
cipants determined the timing of food consumption; however,
breakfast was typically consumed between 08:30 and 11:00,
lunch between 12:30 and 16:00, and dinner between 18:30 and
20:00. Additional snack food was available ad libitum through-
out the study, as were water, juice, and caffeine-free soda. Meal
choices were selected by participants from a standardized set of
options provided by the Metabolic Kitchen of the Hospital of
the University of Pennsylvania; chocolate, turkey, bananas, and
caffeinated beverages were prohibited due to their effects on
sleep/alertness. Participants were allowed to ambulate freely
in the laboratory and were not confined totheir beds throughout
the study (excluding assigned sleep periods) but were restricted
from performing more strenuous activities. While not engaged
in study-related activities, participants read books, played
board games, and watched movies.
Statistical Package for the Social Sciences (SPSS) Statistical
Software, version 16.0 (SPSS Inc, Chicago, Illinois), was used
for statistical analyses. Nonparametric analyses were con-
ducted using the total sample to assess the effects of 5 nights
of partial sleep restriction on plasma leptin levels (B2 to
SR5). Mann-Whitney U tests were used for between-group
comparisons, and Wilcoxin signed rank tests were used for
within-group comparisons. Comparisons were also conducted
to assess for differences within demographic groups (sex, race,
age, BMI, and a subset analyses of lean men only). Regression
analyses were completed to assess the predictive value of
demographic variables (sex, BMI, race/ethnicity, age) on
change in leptin levels. Log-transformed scores were used for
regression analyses, and residuals as well as Mahalanobis
distances were examined for outliers and model fit. A 2-by-2
between-groups analysis of covariance (ANCOVA) was also
conducted to assess the effect of further sleep restriction
(FR2) or recovery sleep (RS2) for both male and female parti-
cipants, while controlling for BMI and prior change from B2 to
SR5. Log-transformed data were used for the ANCOVA, as
raw leptin data were not normally distributed.
The mean leptin level for the sleep-restricted participants was
7.88 (+6.59) ng/mL at baseline (B2) and increased to 10.51
(+8.83) ng/mL following 5 nights of partial sleep restriction
(SR5). Leptin levels did not change significantly from B2 to
SR5 within the control group (Z ¼ ?0.18, p ¼ .86). Among
increased from B2 to SR5 in the total sample (Z ¼ ?8.43,
p < .001) as well as among males (Z ¼ ?5.87, p ¼ < .001),
females (Z ¼ ?6.07, p ¼ < .001), African Americans (Z ¼
?6.06, p < .001), and Caucasians (Z ¼ ?5.48, p < .001). Leptin
levels also increased significantly following sleep restriction in
the following subsamples grouped by age and BMI: partici-
pants with higher BMIs (above the median [24.3 kg/m2]: Z ¼
?6.32, p < .001), participants with lower BMIs (below the
median: Z ¼ ?5.55, p < .001), older participants (above the
mean: Z ¼ ?5.67, p < .001), and younger participants (below
the mean: Z ¼ ?6.24, p < .001). Lean male participants (BMI
? 24; n ¼ 26), a subsample similar to participants in most pre-
vious studies, also demonstrated significant elevations in leptin
levels as a result of sleep restriction (Z ¼ ?2.98, p ¼ .003).
Also within the sleep-restriction condition, a comparison of
women and men on leptin change scores indicated that women
demonstrated a greater increase in leptin levels from B2 to
SR5 than men (Z ¼ ?4.77, p < .001; Figure 2). Changes in
leptin were also greater in participants with higher compared
to lower BMI (Z ¼ ?2.09, p ¼ .036). Comparisons of changes
in leptin from B2 to SR5 between other demographic groups
Figure 1. Study design. Control condition (n ¼ 9) received 10 hr
TIB/night. Blood draws were completed between 10:30 and 12:00
following baseline (B2), sleep restriction (SR5), and further sleep
restriction (FR2)/recovery sleep (RS2) nights. Participants without
complete data are not presented. TIB ¼ time in bed.
Simpson et al.49
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(race/ethnicity, age) were nonsignificant (all p values > .14).
See Table 1 for presentation of all means and standard
Regression analysesconducted toassesstherelativecontribu-
tions of different variables to leptin response to sleep restriction
from the nonparametric comparisons presented above (Table 2).
A 2-by-2 between-groups ANCOVA was conducted to
assess the effects of further sleep restriction (FR2) and recovery
sleep (RS2) on leptin levels for men and women, controlling
for prior change in leptin from B2 to SR5 and for BMI. The
independent variables were the recovery groups (further
restriction: FR2; recovery: RS2) and sex (male, female). The
dependent variable was change in log-transformed leptin
scores from SR5 to FR2 or RS2. BMI and change in log-
transformed leptin levels from B2 to SR5 were used as covari-
ates to control for individual differences. After adjustment for
BMI and change in leptin levels from B2 to SR5, there was a
significant effect of recovery group (F(1, 58) ¼ 14.33, p <
.001) with a large effect size (partial eta squared ¼ .20). There
was no interaction between recovery group and sex (F(1, 58)
¼ 0.00 p ¼ .99), but there was a significant main effect of sex
(F(1, 58) ¼ 5.90, p ¼ .018) with a moderate effect size (partial
eta squared ¼ .092). See Figure 3 for presentation of leptin
levels by recovery group.
The current study demonstrates that morning plasma leptin lev-
els increase significantly following 5 nights of partial sleep
restriction with ad libitum access to food. Observed increases
in plasma leptin levels were maintained with further sleep
restriction and decreased with increased sleep opportunity.
These findings were consistent across a diverse sample,
although women and heavier (higher BMI) participants were
observed to have a significantly greater leptin response to sleep
restriction compared to men and participants with lower BMIs.
Results from the current study provide new evidence that
women are differentially vulnerable to the physiological
consequences of sleep restriction. Estimated menstrual phase
did not have a significant effect on either baseline leptin levels
or their response to sleep restriction; as such, it is unlikely that
menstrual phase contributed significantly to the greater, and
more variable, leptin response among women compared to men.
The observed sex differences may, then, be related to
Figure 2. Effects of sleep restriction on leptin levels in male and
female study participants from baseline (B2) to post–5 nights of partial
sleep restriction (SR5). Horizontal lines represent mean values: male
participants ¼ 1.11 ng/mL, female participants ¼ 4.29 ng/mL. Mean
body mass index (BMI) ¼ 25.68 kg/m2for male participants and
23.46 kg/m2for female participants.
Table 1. Mean Leptin Levels at Baseline (B2) and After 5 Nights of
Sleep Restricted to 4 hr Time in Bed/Night (SR5) for Sleep-
Restricted and Control Participants and Subgroups of Sleep-
Participants and Subgroups
Leptin Levels (ng/mL),
Sleep-restricted participants (n ¼ 136)
Control participants (n ¼ 9)
Subgroups of sleep-restricted participants
Males (n ¼ 71)
Females (n ¼ 65)
African Americans (n ¼ 75)
Caucasians (n ¼ 54)
Below median BMI (n ¼ 68)
Above median BMI (n ¼ 68)
Below mean age (n ¼ 77)
Above mean age (n ¼ 59)
NOTES: Subgroups of control participants are not presented due to sample
size. Data from sleep-restricted participants who indicated race/ethnicity other
than Caucasian or African American are not presented separately. Median
body mass index (BMI) ¼ 24.3 kg/m2. Mean age ¼ 30.63 years.
aSubgroups differed significantly at baseline (all p values < .002).
7.88 (6.59) 10.51 (8.83)
10.88 (6.49) 11.03 (6.32)
11.41 (7.20) 15.70 (9.52)
9.28 (7.28) 12.29 (9.50)
5.58 (4.68)7.48 (6.34)
9.97 (7.21) 13.19 (9.87)
9.34 (6.98) 11.97 (8.91)
Table 2. Contributions of Demographic Variables to Leptin Response
to Sleep Restriction From Baseline to Post–5 Nights of Partial Sleep
Restriction (B2 to SR5)
VariableB SE B
NOTE: R2¼ .32. Results of analysis of variance (ANOVA): F(4, 124) ¼ 14.45, p
< .001. B ¼ unstandardized beta (regression) coefficient; SE B ¼ standard error
of B; b ¼ standardized beta (regression) coefficient.
aOnly African American and Caucasian sleep-restricted participants included in
* p < .001.
50Biological Research for Nursing 12(1)
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physiological (e.g., gonadal steroids, Rosenbaum, Pietrobelli,
Vasselli, Heymsfield, & Leibel, 2001; hypothalamic-pituitary-
adrenal axis reactivity, Uhart, Chong, Oswald, Lin, & Wand,
2006) orpsychological differences (e.g.,differences infoodcon-
sumption in response to stress; Zellner et al., 2006). In any case,
it is likely that these differences resulted from an interaction
between biological factors and behavioral outcomes (e.g., food
choices and amount consumed) in response to stress.
While the majority of experimental sleep-restriction
research has enrolled male-only samples, two prior epidemio-
logic studies have documented increased cardiovascular risk
(incident myocardial infarction, hypertension) associated with
short sleep durations among women but not men (Cappuccio
et al., 2007; Ikehara et al., 2009), and one additional study has
documented associations between short sleep durations and
inflammatory markers (interleukin [IL]-6, high sensitivity
C-reactive protein [hs-CRP]) among women but not men
(Miller et al., 2009). Furthermore, the finding that increases
in leptin following sleep restriction were significantly greater
among women and heavier individuals also has intriguing par-
allels with epidemiological evidence that rates of both obesity
(BMI > 30) and extreme obesity (BMI > 40) are higher among
women compared to men and that increases in rates of obesity
and extreme obesity from 1988–1994 to 1999–2000 were
larger among women (Flegal et al., 2002). These studies pro-
vide additional support for the sex-based difference observed
in the current study, which suggests that effects on leptin may
be one biological pathway through which women may be more
vulnerable to health risks from behavioral factors (e.g.,
Observed increases in leptin during periods of sleep restric-
tion in the current study were similar to percentage changes
reported during periods of ‘‘overfeeding’’ (Chin-Chance,
Polonsky, & Schoeller, 2000) and could reflect simply an
increased food intake due to increased time awake. However,
the increases in leptin levels observed during one study of total
sleep restriction with controlled food intake (Shea et al., 2005)
suggest that the findings of the current study are not a result of
increased food intake alone. Several studies have reported
increases in hunger during fasting or calorically controlled
sleep restriction (Schmid et al., 2008; Spiegel, Tasali, et al.,
2004), but reports of food consumption during sleep restriction
have been mixed (Nedeltcheva et al., 2009; Schmid, Dilba,
Halischmid, Jauch-Chara, & Schultes, 2007). As such, there
is some evidence that hunger increases during sleep restriction
when access to food is controlled and limited evidence that pat-
terns of food intake may change during sleep restriction. These
changes may occur simply as a result of increased time awake
(Saper, Chou, & Elmquist, 2002), as a mechanism to moderate
boredom or stress (Dallman et al., 2003; Vgontzas et al., 2008),
or as part of a more complex interaction with orexin systems
associated with maintenance of wakefulness and feeding beha-
viors (Willie, Chemelli, Sinton, & Yanagisawa, 2001). It is also
possible that food consumption, itself, at an adverse circadian
phase (e.g., nighttime) may play a role.
It is a limitation of the current study that exact energy intake
and expenditures were not assessed, particularly with respect to
changes in leptin between differing amounts of sleep opportu-
nity. Another methodological limitation was the use of a single
blood draw per sampling day rather than sampling leptin levels
over the course of a 24-hr day. While significant relationships
between sleep duration and leptin levels based on a single
blood draw have previously been reported in the literature
(e.g., Taheri et al., 2004; van Leeuwen et al., 2009), this meth-
odology may not adequately capture changes in the diurnal
rhythm of leptin in response to sleep restriction (e.g., Mulling-
ton et al., 2003). It is less clear why our study findings differ
from those of the one laboratory study that also provided free
access to food (Nedeltcheva et al., 2009), though differences
in measurement parameters (fasting compared to nonfasting,
24-hr profile compared to a single blood draw, differences in
sample size) suggest that the neuroendocrine response to sleep
restriction and food intake may be sensitive to the experimental
conditions under which leptin is assessed. The robustness of the
current findings across demographic groups (sex, age, race/
ethnicity, BMI), however, demonstrates that observed changes
in leptin are relatively consistent within our experimental
parameters, which more closely resemble the real-world
environment than previous studies that strictly controlled or
restricted food intake. Additional research is needed to clarify
the respective contributions of short- and long-term sleep
restriction and food intake on leptin levels and body weight.
While the current findings differ from previous studies that
have restricted or controlled food intake and generally
observed decreases in leptin levels (Gomez-Merino et al.,
2002, 2005; Guilleminault et al., 2003; Gundersen et al.,
Figure 3. Leptin levels at all three time points for male and female
participants completing 2 days of further sleep restriction or recovery
sleep. Raw data (not controlling for body mass index [BMI]), split by
sex, is presented. B2 ¼ baseline; FR2 ¼ post–2 days of further sleep
restriction; RS2 ¼ post–2 days of increased sleep time; SR5 ¼ post–5
nights of partial sleep restriction.
Simpson et al.51
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2006; Mullington et al., 2003; Nindl et al., 2006; Schmid et al.,
2008; Spiegel, Leproult et al., 2004; Spiegel, Tasali, et al.,
2004), these disparate findings may still reflect the same epi-
phenomenon: sleep restriction may cause an initial decrease
in leptin levels, which stimulates appetite and results in
increased food intake, leading to elevated leptin levels. How-
ever, this study is the first to document any differential
response across demographic groups within the population.
Findings from the current study are significant because the
experimental conditions used more closely resemble the
real-world conditions under which sleep restriction occurs—
environments where access to food is plentiful and physical
activity is limited due to increasingly sedentary lifestyles.
Additionally, this study provides novel evidence of a differen-
tial vulnerability of women and individuals with higher BMIs
to the biological effects of sleep restriction. Results from the
current study demonstrate that sleep restriction can result
in direct physiological changes that are relevant to obesity, par-
ticularly given the prevalence of shortened sleep and increasing
rates of obesity in modern society. This research is of relevance
to nursing practice as it emphasizes that obtaining adequate
sleep is an important health behavior and that inadequate sleep
is associated with health risks, as well as identifies populations
that may be more vulnerable to the deleterious effects of sleep
loss. These findings have both clinical and occupational (e.g.,
nursing shift work) significance.
Leptin assays were conducted by the RIA/Biomarker Core Laboratory
at the University of Pennsylvania School of Medicine (Technical
Director: Heather Collins, PhD).
Declaration of Conflicting Interests
The author(s) declared no conflicts of interest with respect to the
authorship and/or publication of this article.
The author(s) disclosed receipt of the following financial support for
the research and/or authorship of this article: National Institute of
Health (NIH NR004281, F31 AG031352) and the National Center for
Research Resources (UL1RR024134).
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