Proceedings
oftheNutritionSo
ciety
The Joint Winter Meeting between the Nutrition Society and the Royal Society of Medicine held at The Royal Society of Medicine,London on 8–9 December 2015
Conference on ‘Roles of sleep and circadian rhythms in the origin and nutritionalmanagement of obesity and metabolic disease’Symposium 4: Influence of lifestyle and genetics
The role of sleep duration in diabetes and glucose control
Alia Alnaji1,2, Graham R. Law1 and Eleanor M. Scott1*1Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
2Department of Public Health, General Directorate of Health Affairs in Eastern Province, Ministry of Health,Saudi Arabia
Sleep curtailment is common in the Westernised world and coincides with an increase in theprevalence of type 2 diabetesmellitus (T2DM). This review considers the recently published evi-dence forwhether sleep duration is involved in the development ofT2DMinhuman subjects andwhether sleep has a role to play in glucose control in peoplewho have diabetes. Data from large,prospective studies indicate a U-shaped relationship between sleep duration and the develop-ment of T2DM. Smaller, cross-sectional studies also support a relationship between shortsleep duration and the development of both insulin resistance and T2DM. Intervention studiesshow that sleep restriction leads to insulin resistance, with recent sleep extension studies offeringtantalising data showing a potential benefit of sleep extension on glucose control and insulin sen-sitivity. In peoplewith established diabetes the published literature shows anassociationbetweenpoor glucose control and both short and long sleep durations. However, there are currently nostudies that determine the causal direction of this relationship, nor whether sleep interventionsare likely to offer benefit for people with diabetes to help them achieve tighter glucose control.
Diabetes: Glucose: Sleep: Circadian: Clock: Insulin resistance
Life on earth is governed by the 24-h cycle of light anddarkness associated with the rotation of the earth.Normally metabolic and physiological pathways arecoordinated to this 24-h cycle by an endogenous clockenabling our bodies to coordinate appropriate physio-logical processes to the time of day. Research in animalsand human subjects suggests that the advent of a 24/7lifestyle that disrupts our natural sleep cycles and theiralignment to the external light–dark cycle is importantin the regulation of energy balance and glucose metabol-ism(1–3). Sleep curtailment has become a prevalent behav-iour in the Western and developing world where it isestimated that average sleepdurationhasdeclinedbyalmost2 h in the past 50 years(4). In the USA and UK, a third ofthe population report getting <7 h sleep per night(5,6).Coinciding with this there has been an explosion in theprevalence of type 2 diabetes mellitus (T2DM), raising theimportant question ofwhether there is a causal link between
the two. This review will specifically consider the recentlypublished evidence for whether sleep duration is involvedin the development of T2DM in human subjects. It will nei-ther appraise the considerable number of studies lookingpredominantly at the role of sleep in the development ofobesity,nor itwilladdresstheseparate,but related, literaturelinking sleep-related breathing disorders to obesity andT2DM. Having considered the role of sleep duration perse in the development of diabetes, the evidence for whethersleep duration has a role to play in glucose control in peoplewho have diabetes is reviewed.
Association between sleep duration and the risk oftype 2 diabetes
Evidence from prospective studies
Several large cohort studies have investigated the associ-ation between sleep duration and the risk of subsequently
*Corresponding author: Dr E. M. Scott, email [email protected]: HR, hazard ratio; T2DM, type 2 diabetes mellitus.
Proceedings of the Nutrition Society (2016), 75, 512–520 doi:10.1017/S002966511600063X© The Authors 2016 First published online 23 June 2016
https://www.cambridge.org/core/terms. https://doi.org/10.1017/S002966511600063XDownloaded from https://www.cambridge.org/core. IP address: 54.39.106.173, on 14 Feb 2021 at 01:46:15, subject to the Cambridge Core terms of use, available at
Proceedings
oftheNutritionSo
ciety
developing T2DM, studied over varying lengths of follow-up(7–16). Details of their study design and outcomes areshown in Table 1. Several big studies in the USA andGermany have shown a U-shaped association betweensleep duration and increased risk of T2DM(7–9). The stud-ies relied on subjective measures, with sleep duration self-reported at baseline, and T2DM incidence was mainlyby self-report of physician’s diagnosis.Using 7 h sleep dur-ation per night as a reference category, those with shorterand longer sleep duration were significantly more likely todevelop T2DM over the follow-up period of 5–15 years(risk estimates ranging between 1·47 and 1·95 for shortsleep duration, and between 1·40 and 3·12 for long sleepduration). Regression models employed in the analysiswere adjusted for many potential confounders, mainly;age, physical activity, BMI, alcohol consumption, ethni-city, education, marital status, depression and history ofhypertension.Not all studies have shown thisU-shaped re-lationship however. A large Australian study of >192 000adults used information recorded in medical insurancerecords(10) and reported a positive association betweenshort (but not long) sleep duration and subsequent inci-dence of T2DM. However, T2DM incidence was deter-mined from hospital admission records and so those whowere not admitted to hospital during the follow-up periodcould not be identified as T2DM, which might have led tounderestimation of the actual diabetes incidence. In add-ition, the follow-up period was relatively short (mean dur-ation 2·3 years). Another prospective study examined theassociation of sleep duration with development ofimpaired fasting glucose over 6 years follow-up(11),with 6–8 h sleep duration as a reference category, short(but not long) sleepers had higher odds of developingimpaired fasting glucose (OR 3·0, 95 % CI 1·05, 8·59;OR 1·6, 95 % CI 0·45, 5·42 for short and long sleep dura-tions, respectively). A Finnish study in overweight indivi-duals with impaired glucose tolerance found an increasedrisk of T2DMonly in participants with long sleep duration⩾9 h (hazard ratio (HR) 2·29, 95 % CI 1·38, 3·80)(14).Finally, two recent meta-analyses of nine(17) and four-teen(18) prospective cohort studies have also confirmedthe U-shaped relationship (Fig. 1). A couple of other stud-ies have investigated the association between short com-pared with normal sleep duration and the risk of T2DMwithout examining for a U-shaped relationship. The firstshowed that sleeping ⩽7 h per night was associated withhigher odds of developing T2DM after 6 years follow-up(OR 1·96, 95 % CI 1·10, 3·50)(12). Models were adjustedfor age, sex, physical activity, smoking habit, weightgain and abnormal glucose regulation at baseline. Thestudy also found that the odds of becoming obese weresignificantly higher in subjects who slept ⩽7 h per night(OR 1·99, 95 % CI 1·12, 3·55). There was a lack of associ-ation between sleep duration and TD2M at 11 yearsfollow-up that could be related to the attrition in studypopulation over time and to the mediation effect exhibitedby adjusting for weight gain in the model. The secondstudy found a higher odds of T2DM after 2 years follow-up, sleeping ⩽5 h compared with >7 h sleep duration(OR 5·37, 95 % CI 1·38, 20·91)(13). The logistic regressionmodels were however adjusted for fasting plasma glucose,
an integral feature of the outcome measure, T2DM. Thisleads to a statistical phenomenon known as mathematicalcoupling thus rendering the result spurious(19,20).
Extending the understanding of the relationship be-tween sleep duration and risk of T2DM the impact ofa change in sleep duration over time has also been inves-tigated. In the Whitehall II study in the UK, change insleep duration was calculated for participants withoutdiabetes at the beginning and end of four 5-year cyclesand T2DM incidence was observed at the end of the sub-sequent cycle(15). Another, rather convoluted, prospectivestudy (the Nurses’ Health study) examined whether his-toric changes in women’s sleep duration over the preced-ing 14 years was associated with developing T2DM overthe subsequent 12-year follow-up(16). In both studies, lo-gistic regression models showed higher risk of developingT2DM in participants with chronic short sleep duration(⩽5·5–6 h; Whitehall II study OR 1·35, 95 % CI 1·04,1·76; Nurses’ Health study HR 1·10, 95 % CI 1·001,1·21) and in those with an increase of ⩾2 h sleep duration(Whitehall II study OR 1·65, 95 % CI 1·15, 2·37; Nurses’Health study HR 1·15, 95 % CI 1·01, 1·30) comparedwith those who maintained 7–8 h sleep duration. Afteradjusting for BMI both associations were attenuated,suggesting that BMI is a mediator in the association.These studies suggest that the adverse metabolic influ-ence of short sleep duration may not be ameliorated byincreasing sleep duration later in life.
Taken together, these large prospective studies whichinclude both men and women, and a wide range ofages show that a U-shaped relationship exists betweenself-reported sleep duration and the development ofT2DM. Given the increasing societal pressures to sleepless, these data are very persuasive of short sleep durationbeing implicated in the co-existent T2DM epidemic.
Evidence from cross-sectional studies
Whilst they do not carry the same weight as prospectivestudies, there have been several recent cross-sectionalstudies that suggest there may be some key sociodemo-graphic factors that influence the relationship betweensleep duration and T2DM, and these are summarisedin Table 2. Again a U-shaped association between sleepduration (over a 24 h period) and T2DM was observedin 130 943 adults, aged 18–85 years, using data fromthe National Health Interview Survey from 2004 to2011(21). However, short and long sleep durations weremore strongly associated with T2DM in white partici-pants than in black. Adjustment for socioeconomic statusand other health behavioural factors attenuated the asso-ciations in both groups and remained significant only inwhite participants. An additional cross-sectional studyusing the National Health Interview Survey data, fromyears 2004 to 2005, also reported a U-shaped associationbetween sleep duration and T2DM(22). A Chinese studyshowed that longer sleep duration over a 24 h periodwas positively associated with having the metabolic syn-drome and T2DM, but only in women(23). Objectivelymeasured sleep duration (using wrist actigraphy) showeda significant association between shorter sleep duration
The role of sleep duration in diabetes and glucose control 513
https://www.cambridge.org/core/terms. https://doi.org/10.1017/S002966511600063XDownloaded from https://www.cambridge.org/core. IP address: 54.39.106.173, on 14 Feb 2021 at 01:46:15, subject to the Cambridge Core terms of use, available at
Proceedings of the Nutrition Society
Table 1. Prospective studies on sleep duration and the risk of developing type 2 diabetes mellitus (T2DM)
Author, year Country Participant Study design Exposure Outcome Result Comment
Gangwisch et al.,2007(8)
USA 8992 adult aged 32–68years from the NHANES I
Prospective cohort Subjective nighttimesleep duration
T2DM incidenceover 8–10 yearsfollow-up period
U-shaped associations
Yaggi et al., 2006(7) USA 1564 men aged 40–70 yearsfrom the MassachusettsMale Aging study
Prospective cohortstudy
Subjective nighttimesleep duration
T2DM incidenceover 15-yearfollow-up period
U-shaped associations
Kowall et al.,2016(9)
Germany 4814 adults aged 45–75years from the HeinzNixdorf Recall study
Prospective cohortstudy
Subjective nighttimesleep duration
T2DM incidenceover 5-yearfollow-up period
U-shaped associations
Holliday et al.,2013(10)
Australia 192 728 adults aged ⩾45selected from medicalinsurance database
Prospective cohortstudy
Subjective sleepduration
T2DM incidenceover a meanfollow-up periodof 2·3 years
Positive association, onlyshort sleep duration
Diabetes incidentsextracted from hospitaladmission or mortalityelectronic records, shortfollow-up period
Rafalson et al.,2010(11)
USA 363 participants; 91 cases,272 controls, aged 35–79years
nested case-control Subjective sleepduration (weekdaysonly)
Impaired fastingglucose
Positive association, onlyshort sleep duration
Tuomilehto et al.,2009(14)
Finland 522 participants aged 40–64years without diabetesrandomly allocated eitherto a study arm or to acontrol arm
Two Prospectivecohorts based onarms of arandomisedcontrolled trial
Subjective sleepduration
T2DM incidenceover 7-yearfollow-up period
Positive association, onlylong sleep duration
Only in the control armcohort
Gutiérrez-Repisoet al., 2014(12)
Spain 1145 randomly selectedparticipants aged 16–65years from the Pizzarastudy
Prospective cohort Subjective nighttimesleep duration
T2DM incidenceat 6 and 11 yearsfollow-up
Positive association only at6-year follow-up
Change in sleep durationover the 11-yearfollow-up
Kita et al., 2012(13) Japan 3570 adults aged 35–55years
Prospective cohort Subjective sleepduration and sleepquality
T2DM incidenceafter 2-yearfollow-up)
Positive spuriousassociation
Statistical issues
Ferrie et al.,2015(15)
UK 5613 adults aged 35–55years from the Whitehall IIstudy
Prospective cohort,four 5-year cycles
Change in nighttimesleep duration inthe following cycle
T2DM incidenceat the end ofsubsequentcycle
Positive association,increase ⩾2 h
Association could bemediated by weight gain
Cespedes et al.,2016(16)
USA 59 031 middle aged to oldwomen without diabetes
Prospective cohortstudy
Change in sleepduration over 14years
T2DM incidenceover 12-yearfollow-up period
Positive association,increase ⩾2 h
Association only withincrease in sleep duration⩾2 h/d, Change in sleepduration from a historicbaseline to time ofenrolment
A.Alnaji
etal.
514
https://ww
w.cam
bridge.org/core/terms. https://doi.org/10.1017/S002966511600063X
Dow
nloaded from https://w
ww
.cambridge.org/core. IP address: 54.39.106.173, on 14 Feb 2021 at 01:46:15, subject to the Cam
bridge Core terms of use, available at
Proceedings
oftheNutritionSo
ciety
and having impaired fasting glucose and diabetes, butdid not find any ethnic differences in a multi-ethnicstudy(24).
Association between sleep duration and the risk ofinsulin resistance
One of the key features of T2DM is impaired insulinmediated glucose uptake, otherwise known as insulin re-sistance. This precedes the glucose abnormalities andclinical manifestation of T2DM, often by many years.A selection of both observational and intervention stud-ies have recently explored the relationship between sleepduration and measures of insulin resistance and these aresummarised in Table 3.
Evidence from cross-sectional studies
A small study compared the self-reported sleep durationin insulin-resistant individuals (n 35) with that seen ininsulin-sensitive individuals (n 21). Those with insulin re-sistance slept 43 min less per night (P = 0·018). The studyalso found that 60 % of insulin-resistant participantsslept <7 h in comparison with only 24 % only of insulin-sensitive participants (P = 0·013), though no adjustmentfor potential confounders was performed(25).
Whilst observational studies are of interest, it is well-designed interventional studies that really help us understandthe role of sleep duration in the development of insulin resist-ance and glucose tolerance. There have been a cluster ofthese published recently looking at the metabolic effects ofboth sleep restriction and sleep extension.
Evidence from sleep restriction clinical studies
Multiple small laboratory-based crossover studies onhealthy young participants have looked at the effect ofsleep restriction on insulin sensitivity and glucose toler-ance(26–30). Sleep restriction was associated with reducedinsulin sensitivity in all the studies (except one(30)), withreduced glucose tolerance in one of them(27). The studythat found no effect on glucose or insulin aimed to
Fig. 1. U-shaped relationship between sleep duration and risk oftype 2 diabetes mellitus (adapted from Shan et al.(17)).
Table
2.Cross-sec
tiona
lstudieson
slee
pdurationan
dtheris
kof
dev
elop
ingtype2diabetes
mellitus
(T2D
M)
Autho
r,ye
arCou
ntry
Partic
ipan
tStudydes
ign
Exp
osure
Outco
me
Res
ult
Com
men
t
Jack
son
etal.,
2013
(21)
USA
13094
3ad
ults
aged
18–85
years
from
theNHIS
(yea
rs20
04–20
11)
Cross-sec
tiona
lSub
jectiveslee
pdurationin
a24
hperiod
Self-reportedT2
DM
status
U-sha
ped
asso
ciations
Stron
gera
ssoc
iatio
nin
white
pop
ulation
Bux
ton&
Marce
lli,
2010
(22)
USA
5650
7ad
ults
from
theNHIS
(yea
rs20
04–20
05)
Cross-sec
tiona
lSub
jectiveslee
pdurationin
a24
hperiod
Self-reportedch
ronic
disea
sesinclud
ingT2
DM
U-sha
ped
asso
ciations
Multilev
ellogistic
regres
sion
Wuet
al.,
2015
(23)
China
2518
4ad
ults
mea
nag
e63
years
from
theDon
gfen
g-To
ngjiCoh
ort
stud
y
Cross-sec
tiona
lSub
jectiveslee
pduration
Riskof
metab
olic
synd
romeinclud
ingT2
DM
Noas
sociationwith
nigh
ttim
eslee
pduration
Pos
itive
asso
ciation
with
day
timena
pping
duration
Bak
keret
al.,
2015
(24)
USA
2151
partic
ipan
tag
ed45
–84
years
from
theMulti-EthnicStudyof
Atheros
cleros
is
Cross-sec
tiona
lObjectiveslee
pduration
Diabetes
Noas
sociation
Mod
elad
justed
for
OSA
NHIS,Nationa
lHea
lthInterview
Surve
y;OSA,o
bstructiveslee
pap
noea
.
The role of sleep duration in diabetes and glucose control 515
https://www.cambridge.org/core/terms. https://doi.org/10.1017/S002966511600063XDownloaded from https://www.cambridge.org/core. IP address: 54.39.106.173, on 14 Feb 2021 at 01:46:15, subject to the Cambridge Core terms of use, available at
Proceedings of the Nutrition Society
Table 3. Studies on sleep duration and development of insulin resistance
Author, year Country Participant Study design Exposure Outcome Result Comment
Liu et al.,2013(25)
USA Fifty-six non-diabeticoverweight–obeseparticipants
Cross sectional Subjective sleepduration
Insulin sensitivity Positive association Only P-values reported
Broussardet al., 2012(26)
USA Seven young healthyparticipants
Crossover clinical study Sleep restriction Insulin sensitivity Positive association
Nedeltchevaet al., 2009(27)
USA Eleven young-middleaged healthyparticipants
Crossover clinical study Sleep restriction Insulin sensitivity andglucose tolerance
Positive association
Wang et al.,online2016(28)
USA Fifteen young healthynon-obeseparticipants
Crossover clinical study Time-in-bed restrictionby 1–3 h for threenights
Insulin sensitivity andglucose tolerance
Positive associationwith insulinsensitivity
No association withglucose tolerance
Donga et al.,2010(1)(29)
TheNetherlands
Nine healthyparticipants, mean age44·6 years
Crossover clinical study Sleep restriction Insulin sensitivity Positive association
St-Onge et al.,2012(30)
USA Twenty-seven healthyyoung non-obeseadults
Crossover clinical study Time in bed restricted to4 h
Insulin sensitivity No association Participants hadcontrolled diet and lostweight during the study
Robertsonet al., 2013(31)
UK Nineteen healthy younglean men
Randomised controlledtrial
Around 1·5 h sleeprestriction per night for3 weeks
Insulin sensitivity Positive associationonly at the end offirst week
Absence of an overalleffect of sleep restrictionon insulin sensitivity
Broussardet al., 2016(32)
USA Nineteen healthy younglean men
Crossover clinical study 2 d of catch-up sleep Recovery of insulinsensitivity
Positive association
Leproult et al.,2015(33)
Belgium Sixteen healthy youngnon-obese adults withchronic sleeprestriction
Crossover clinical study Around 1 h sleepextension per night for6 weeks
Fasting glucose andinsulin levels
No difference in pre-andpost-interventionlevels
Moderate correlationbetween relative changein sleep duration andrelative change infasting glucose andinsulin levels
A.Alnaji
etal.
516
https://ww
w.cam
bridge.org/core/terms. https://doi.org/10.1017/S002966511600063X
Dow
nloaded from https://w
ww
.cambridge.org/core. IP address: 54.39.106.173, on 14 Feb 2021 at 01:46:15, subject to the Cam
bridge Core terms of use, available at
Proceedings
oftheNutritionSo
ciety
determine the hormonal effects of restricting sleep dur-ation under controlled feeding conditions(30). A con-trolled diet was provided and the participants lostweight in both the habitual and short sleep phases. It ispossible that in the context of negative energy balance,acute short sleep duration does not lead to a state ofincreased insulin resistance. These studies were all per-formed in controlled laboratory-based environmentsand explored acute and often severe sleep restriction.One recent study has examined participants in theirhome environment to determine if milder and morechronic sleep restriction, akin to daily life, has a role toplay(31). Nineteen healthy, young, normal-weight menwith habitual sleep durations of 7·0–7·5 h and no sleepdisturbances were randomised to either study arm (1·5h reduction in habitual bedtime) or control arm (habitualbedtime) for 3 weeks. Sleep restriction led to a decrease ininsulin sensitivity at the end of first week but then recov-ered to baseline levels.
In summary, these intervention studies are showingthat sleep restriction is associated with the developmentof insulin resistance and impairment of glucose tolerance.Whether these effects are short-lived adaptive responsesto an acute stress, or whether they persist longer termand contribute to the risk of T2DM remains unclear.
Evidence from sleep extension clinical studies
Given that short sleep duration and sleep restriction arelinked to the development of insulin resistance, it is time-ly that a couple of studies are starting to address whethersleep extension has beneficial effects on insulin and glu-cose metabolism.
The first, a crossover study(32) showed that whilst insu-lin sensitivity deteriorates after acute sleep restriction itrecovers after 2 d catch-up sleep. Under laboratory-controlled conditions participants had up to 8·5 h sleepper night for four consecutive nights and up to 4·5 hsleep for another four consecutive nights in a randomisedorder. After the nights of restricted sleep, participantshad two catch-up nights of 10–12 h sleep. Participantshad a 23 % decrease in insulin sensitivity after 4 dsleep curtailment compared with normal sleep.However, insulin sensitivity was restored after 2 d catch-up sleep. Although the study showed that catch-up sleepmay reverse the negative impact of short-term sleep de-privation, the long-term impact of a repeated sleep de-privation and catch-up sleep cycles on diabetes risk isnot known.
The second study investigated whether sleep extensionin the home environment has a positive impact on glu-cose metabolism in healthy adults with chronic sleep cur-tailment(33). Sixteen young healthy non-obese adults,mostly females, had 2 weeks habitual time in bed fol-lowed by 6 weeks 1 h/d extension time in bed. Glucoseand insulin were assayed at the end of the two periods.During the intervention phase participants mostly wentto bed an hour earlier and had higher sleep duration dur-ing weekdays but maintained the same sleep durationduring weekends. The study indicated no significantdifference between pre- and post-intervention fasting
glucose and insulin levels, though no statistics wereshown(34). A moderate linear relationship was reportedbetween the relative change in sleep duration and therelative change in fasting glucose (r= +0·65, P = 0·017)and insulin levels (r =−0·57, P = 0·053); however, wecannot quantify these relationships nor state if theywere statistically significant, without a reported estimatemeasure of associations.
In conclusion, these sleep extension studies, offer tan-talising data supporting a potential benefit of sleep exten-sion on glucose control and insulin sensitivity. Muchmore work is clearly needed in this area.
Association between sleep duration and glycaemiccontrol in patients with diabetes
Given the mounting evidence supporting a relationshipbetween sleep duration and the development of insulin re-sistance and T2DM, it is relevant to consider whethersleep duration has an impact on glycaemic control in peo-ple with established diabetes. Most studies to date arecross-sectional with sample size ranging from as low aseighteen participants to as high as 8543 participants,and these are summarised in Table 4. Most of these studiesassessed glycaemic control using HbA1c except one thatused capillary glucose levels(35). Sleep parameters weremainly self-reported except for three studies that measuredsleep objectively using wrist actigraphy(35–37).
Evidence from cross-sectional studies using subjectivelyreported sleep duration
Okhuma et al. showed that shorter and longer sleep dura-tions were associated with a higher HbA1c level com-pared with a sleep duration of 6·5–7·4 h in T2DMpatients (Fig. 2)(38). Sleep duration including naps wasself-reported. This U-shaped association was not attenu-ated after adjusting for BMI, total energy intake and de-pressive symptoms. A similar U-shaped relation wasreported in a large Korean study, which included partici-pants with both T1DM and T2DM(39). The associationbetween short sleep duration and poor glycaemic controlwas strongest for females and participants below the ageof 65 years. However, these associations was attenuatedafter adjusting for BMI and waist circumference andno association was observed after further adjustmentfor treatment status, duration of diabetes, and daily en-ergy intake. Conversely, only longer sleep duration wasassociated with poor glycaemic control in T2DMpatients in a large Chinese(40) and a smaller Taiwanesestudy(41). Perceived sleep debt but not sleep durationwas positively associated with HbA1c in AfricanAmericans with T2DM without diabetes complicationsand not using insulin(42).
Evidence from cross-sectional studies using objectivelymeasured sleep duration
Using wrist actigraphy to objectively measure sleep para-meters for three consecutive days in the home environ-ment, Trento et al. found no difference in sleep duration
The role of sleep duration in diabetes and glucose control 517
https://www.cambridge.org/core/terms. https://doi.org/10.1017/S002966511600063XDownloaded from https://www.cambridge.org/core. IP address: 54.39.106.173, on 14 Feb 2021 at 01:46:15, subject to the Cambridge Core terms of use, available at
Proceedings of the Nutrition Society
Table 4. Studies on sleep and glycaemic control in patients with diabetes
Author,year Country Participant Study design Exposure Outcome Result Comment
Ohkumaet al.,2013(38)
Japan 4870 adults, aged ⩾20years with T2DM
Cross-sectional Subjective sleep durationincluding naps
Glycaemic control(HbA1c)
U-shapedassociations
Kim et al.,2013(39)
Korea 2134 adults, aged > 20years with T1DM orT2DM
Cross-sectional Subjective daily sleepduration
Glycaemic control(HbA1c)
Positiveassociations
J-shaped trend with HbA1c; stronger infemales and in the younger age group (<65years). Association disappear after adjustingfor more covariate in the logistic regressionmodel
Zhenget al.,2015(40)
China 8543 adults, aged ⩾40years with T2DM orimpaired glucosetolerance
Cross-sectional Subjective nighttimesleep duration
Glycaemic control(HbA1c, FPG, PPG)
Positiveassociation withlong sleepduration
Only adjusted means and P-values reportedbut no estimate of association
Tsai et al.,2012(41)
Taiwan Forty-six adults, aged43–83 years withT2DM
Cross-sectional Subjective sleep durationand quality (PSQI)
Glycaemic control,HbA1c
Positiveassociation
Participants with diabetic complication ormajor co-morbidities were excluded.association only with sleep efficiency andPSQI score of 8 or more but not sleepduration
Knutsonet al.,2006(42)
USA 161 African Americans,mean age 57 yearswith T2DM
Cross-sectional Subjective sleep durationand sleep quality,modified PSQI andperceived sleep debt
Glycaemic control(HbA1c)
Positiveassociation
Sleep debt association only in participantswithout diabetic complication or not usinginsulin. Sleep quality only in participants withdiabetic complication or using insulinassociation
Trentoet al.,2008(36)
Italy Forty-sevenmiddle-aged adultswith T2DM and 23healthy controls
Cross-sectionalstudy
Objective sleepparameters; durationand quality using wristactigraphy
Glycaemic control(HbA1c) in T2DMgroup
Positiveassociation
Weak negative correlation with sleepefficiency and mild positive correlation withmoving time while asleep. No estimatemeasures of association reported
Borel et al.,2013(37)
France Seventy-nine adults,median age 40 yearswith T1DM
Cross-sectionalstudy
Objective sleepparameters using wristactigraphy
Glycaemic control(HbA1c)
Positiveassociation
Baroneet al.,2015(35)
Brazil Eighteen young adult,aged 20–38 years withT1DM
Cross-sectional Objective sleepmeasures using wristactigraphy
Glycaemic control(average glucosefrom glucometerreading)
No association Methodological issues
FPG, fasting plasma glucose; PPG, postprandial glucose; PSQI, Pittsburgh Sleep Quality Index; T2DM, type 2 diabetes mellitus.
A.Alnaji
etal.
518
https://ww
w.cam
bridge.org/core/terms. https://doi.org/10.1017/S002966511600063X
Dow
nloaded from https://w
ww
.cambridge.org/core. IP address: 54.39.106.173, on 14 Feb 2021 at 01:46:15, subject to the Cam
bridge Core terms of use, available at
Proceedings
oftheNutritionSo
ciety
between T2DM and control subjects(36). T2DM sleepquality was found to correlate slightly with glycaemic con-trol, while no correlation with sleep duration wasreported. Conversely, Borel et al. shown that T1DMpatients with shorter sleep duration (<6·5 h) had a higherHbA1c than those with longer sleep duration (>6·5 h;mean 8·5 v. mean 7·7 %; P= 0·001)(37). In an adjusted re-gression model shorter sleep duration was associated with0·64 % increase in mean HbA1c level compared withlonger sleep duration but no 95 % CI or P-value werereported. Participants with short sleep duration werealso more likely to have obstructive sleep apnoea and asthis was not considered in the analysis, part of the differ-ence reported could be attributed to it.
Finally Barone et al. assessed the association betweenobjectively measured sleep parameters using wrist acti-graphy and glycaemic control using capillary glucoselevels from glucometer in a group of eighteen youngadults with T1DM(35). They showed a positive correl-ation between the average amount of rest at night andboth average glucose levels (r= 0·5404; P = 0·0697) andglycaemic variability (r= 0·5706; P= 0·0527). No esti-mate measure of the association nor adjustment for anypotential confounders were made. Moreover, the averagenight rest duration was calculated from 10 d actigraphy,which may have included two weekends for some partici-pants and only one weekend for others, and thus it willbe inevitably incomparable between participants.
In summary, in people with diabetes there also appearsto be evidence of an association between both short andlong sleep durations and worse glucose control.However, these studies are cross-sectional and so evi-dence of causality cannot be inferred. A complicatingfactor when interpreting the relationship between glucoseand sleep in people with diabetes is that extremely poorglucose control is well recognised to cause polyuria, poly-dypsia and nocturia meaning they are awake during thenight. Reverse causality cannot be excluded in these stud-ies as they do not distinguish the severity of glucose con-trol and are likely to include participants experiencing
some of these osmotic symptoms. Randomised clinicaltrials with exposure to sleep duration modification (re-striction or extending) and robust methods of assessingtemporal glucose across the 24 h day and night(43) areneeded to yield more definitive answers.
Conclusions
The recently published literature of both observationaland interventional studies strongly supports a role forboth short and long sleep durations in the developmentof insulin resistance and T2DM. There are insufficientsleep intervention studies to determine whether this riskis modifiable long term. In people with established dia-betes the published literature supports an association be-tween poor glucose control and both short and long sleepdurations. However, there are no studies that determinethe causal direction of this relationship in people withdiabetes, nor whether sleep interventions may offerbenefit in achieving glucose control. This is a fertilefield for future research.
Financial support
A. A. receives financial support from the Ministry ofHealth, Saudi Arabia.
Conflicts of interest
None.
Authorship
E. S. gave the talk at the RSM and conceived the article.A. A. and E. S. drafted the original document. Allauthors reviewed and commented on the draft prior todeveloping the final document.
References
1. Prasai MJ, George JT & Scott EM (2008) Molecularclocks, type 2 diabetes and cardiovascular disease. DiabVasc Dis Res 5, 89–95.
2. Prasai MJ, Pernicova I, Grant PJ et al. (2011) An endocri-nologist’s guide to the clock. J Clin Endocrinol Metab 96,913–922.
3. Tan E & Scott EM (2014) Circadian rhythms, insulin ac-tion, and glucose homeostasis. Curr Opin Clin NutrMetab Care 17, 343–348.
4. Knutson KL, Van Cauter E, Rathouz PJ et al. (2010)Trends in the prevalence of short sleepers in the USA:1975–2006. Sleep 33, 37–45.
5. National Sleep Foundation (2005) Adult sleep habits andstyles. https://sleepfoundation.org/sleep-polls-data/sleep-in-america-poll/2005-adult-sleep-habits-and-styles (accessedApril 2016).
6. Barnes M, Byron C & Beninger K (2013) Sleep patternsand health Analysis of the Understanding Society dataset.
Fig. 2. Higher HbA1c observed in shorter and longer sleepduration in Japanese type 2 diabetes mellitus patients comparedwith 6·5–7·4 h sleep duration (*P < 0·05; **P < 0·01), adapted fromOkhuma et al.(38).
The role of sleep duration in diabetes and glucose control 519
https://www.cambridge.org/core/terms. https://doi.org/10.1017/S002966511600063XDownloaded from https://www.cambridge.org/core. IP address: 54.39.106.173, on 14 Feb 2021 at 01:46:15, subject to the Cambridge Core terms of use, available at
Proceedings
oftheNutritionSo
ciety
http://www.natcen.ac.uk/media/29127/sleep-patterns-and-health.pdf (accessed April 2016).
7. Yaggi HK, Araujo AB & McKinlay JB (2006) Sleep dur-ation as a risk factor for the development of type 2 dia-betes. Diab Care 29, 657–661.
8. Gangwisch JE, Heymsfield SB, Boden-Albala B et al.(2007) Sleep duration as a risk factor for diabetes incidencein a large US sample. Sleep 30, 1667–1673.
9. Kowall B, Lehnich A-T, Strucksberg K-H et al. (2016)Associations among sleep disturbances, nocturnal sleepduration, daytime napping, and incident prediabetes andtype 2 diabetes: the Heinz Nixdorf Recall study. SleepMed (Epublication ahead of print version).
10. Holliday EG, Magee CA, Kritharides L et al. (2013) Shortsleep duration is associated with risk of future diabetes butnot cardiovascular disease: a prospective study andmeta-analysis. PLoS ONE 8, e82305.
11. Rafalson L, Donahue RP, Stranges S et al. (2010) Shortsleep duration is associated with the development ofimpaired fasting glucose: the Western New York HealthStudy. Ann Epidemiol 20, 883–889.
12. Gutierrez-Repiso C, Soriguer F, Rubio-Martin E et al.(2014) Night-time sleep duration and the incidence of obes-ity and type 2 diabetes. Findings from the prospectivePizarra study. Sleep Med 15, 1398–1404.
13. Kita T, Yoshioka E, Satoh H et al. (2012) Short sleep dur-ation and poor sleep quality increase the risk of diabetes inJapanese workers with no family history of diabetes. DiabCare 35, 313–318.
14. Tuomilehto H, Peltonen M, Partinen M et al. (2009) Sleepduration, lifestyle intervention, and incidence of type 2 dia-betes in impaired glucose tolerance: the Finnish diabetesprevention study. Diab Care 32, 1965–1971.
15. Ferrie JE, Kivimaki M, Akbaraly TN et al. (2015) changein sleep duration and type 2 diabetes: the Whitehall IIstudy. Diab Care 38, 1467–1472.
16. Cespedes EM, Bhupathiraju SN, Li Y et al. (2016)Long-term changes in sleep duration, energy balance andrisk of type 2 diabetes. Diabetologia 59, 101–109.
17. Shan Z, Ma H, Xie M et al. (2015) Sleep duration and riskof type 2 diabetes: a meta-analysis of prospective studies.Diab Care 38, 529–537.
18. Anothaisintawee T, Reutrakul S, Van Cauter E et al.(2015) Sleep disturbances compared to traditional risk fac-tors for diabetes development: systematic review andmeta-analysis. Sleep Med Rev 30, 11–24.
19. Archie JP Jr (1981) Mathematic coupling of data: a com-mon source of error. Ann Surg 193, 296–303.
20. Tu Y-K, Maddick IH, Griffiths GS et al. (2004)Mathematical coupling can undermine the statistical as-sessment of clinical research: illustration from the treatmentof guided tissue regeneration. J Dent 32, 133–142.
21. Jackson CL, Redline S, Kawachi I et al. (2013) Associationbetween sleep duration and diabetes in black and whiteadults. Diab Care 36, 3557–3565.
22. Buxton OM & Marcelli E (2010) Short and long sleep arepositively associated with obesity, diabetes, hypertension,and cardiovascular disease among adults in the UnitedStates. Soc Sci Med 71, 1027–1036.
23. Wu J, Xu G, Shen L et al. (2015) Daily sleep duration andrisk of metabolic syndrome among middle-aged and olderChinese adults: cross-sectional evidence from theDongfeng–Tongji cohort study.BMCPublicHealth 15, 178.
24. Bakker JP, Weng J, Wang R et al. (2015) Associations be-tween obstructive sleep apnea, sleep duration, and abnor-mal fasting glucose. The multi-ethnic study ofatherosclerosis. Am J Respir Crit Care Med 192, 745–753.
25. Liu A, Kushida CA & Reaven GM (2013) Habitual shor-tened sleep and insulin resistance: an independent relation-ship in obese individuals. Metabolism 62, 1553–1556.
26. Broussard JL, Ehrmann DA, Van Cauter E et al. (2012)Impaired insulin signaling in human adipocytes after ex-perimental sleep restriction: a randomized, crossoverstudy. Ann Intern Med 157, 549–557.
27. Nedeltcheva AV, Kessler L, Imperial J et al. (2009)Exposure to recurrent sleep restriction in the setting ofhigh caloric intake and physical inactivity results inincreased insulin resistance and reduced glucose tolerance.J Clin Endocrinol Metab 94, 3242–3250.
28. Wang X, Greer J, Porter RR et al. (2016) Short-term mod-erate sleep restriction decreases insulin sensitivity in younghealthy adults. Sleep Health 2, 63–68.
29. Donga E, van Dijk M, van Dijk JG et al. (2010) A singlenight of partial sleep deprivation induces insulin resistancein multiple metabolic pathways in healthy subjects. J ClinEndocrinol Metab 95, 2963–2968.
30. St-Onge MP, O’Keeffe M, Roberts AL et al. (2012) Shortsleep duration, glucose dysregulation and hormonal regula-tion of appetite in men and women. Sleep 35, 1503–1510.
31. Robertson MD, Russell-Jones D, Umpleby AM et al.(2013) Effects of three weeks of mild sleep restriction imple-mented in the home environment on multiple metabolicand endocrine markers in healthy young men.Metabolism 62, 204–211.
32. Broussard JL, Wroblewski K, Kilkus JM et al. (2016) Twonights of recovery sleep reverses the effects of short-termsleep restriction on diabetes risk. Diab Care 39, e40–e41.
33. Leproult R, Deliens G, Gilson M et al. (2015)Beneficial impact of sleep extension on fasting insulin sen-sitivity in adults with habitual sleep restriction. Sleep 38,707–715.
34. Jones B & Kenward MG (2014) Design and Analysisof Crossover Trials. vol. 138. Boca Raton: Taylor &Francis.
35. BaroneMT,WeyD, Schorr F et al. (2015) Sleep and glycemiccontrol in type 1 diabetes. Arch Endocrinol Metab 59, 71–78.
36. Trento M, Broglio F, Riganti F et al. (2008) Sleep abnor-malities in type 2 diabetes may be associated with glycemiccontrol. Acta Diabetol 45, 225–229.
37. Borel AL, Pepin JL, Nasse L et al. (2013) Short sleep dur-ation measured by wrist actimetry is associated with dete-riorated glycemic control in type 1 diabetes. Diab Care36, 2902–2908.
38. Ohkuma T, Fujii H, Iwase M et al. (2013) Impact of sleepduration on obesity and the glycemic level in patients withtype 2 diabetes: the Fukuoka Diabetes Registry. Diab Care36, 611–617.
39. Kim BK, Kim BS, An SY et al. (2013) Sleep duration andglycemic control in patients with diabetes mellitus: KoreaNational Health and Nutrition Examination Survey2007–2010. J Korean Med Sci 28, 1334–1339.
40. Zheng Y, Wang A, Pan C et al. (2015) Impact of nightsleep duration on glycemic and triglyceride levels inChinese with different glycemic status. J Diab 7, 24–30.
41. Tsai YW, Kann NH, Tung TH et al. (2012) Impact of sub-jective sleep quality on glycemic control in type 2 diabetesmellitus. Fam Pract 29, 30–35.
42. Knutson KL, Ryden AM, Mander BA et al. (2006) Role ofsleep duration and quality in the risk and severity of type 2diabetes mellitus. Arch Intern Med 166, 1768–1774.
43. Law GR, Secher A, Temple R et al. (2015) Analysis of con-tinuous glucose monitoring in pregnant women with dia-betes: distinct temporal patterns of glucose associatedwith infant macrosomia. Diab Care 38, 1319–1325.
A. Alnaji et al.520
https://www.cambridge.org/core/terms. https://doi.org/10.1017/S002966511600063XDownloaded from https://www.cambridge.org/core. IP address: 54.39.106.173, on 14 Feb 2021 at 01:46:15, subject to the Cambridge Core terms of use, available at