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ReplacingSittingTimeWithStandingorStepping:
AssociationsWithCardiometabolicRiskBiomarkers
GenevieveN.HealyElisabethA.H.WinklerNevilleOwenSatyamurthyAnuradhaDavidW.Dunstan
EurHeartJ.201536(39):26432649.

AbstractandIntroduction
Abstract

AimsWhileexcessivesittingtimeisrelatedadverselytocardiometabolichealth,itisunknownwhetherstandingisasuitable
replacementactivityorwhetherambulatorymovementisrequired.Usingisotemporalsubstitutionanalyses,wemodelled
crosssectionalassociationswithcardiometabolicriskbiomarkersofreallocatingtime(2h/day)fromsittingtostandingorto
stepping.
MethodsandresultsAsubsampleofparticipantsfromthe2011/12AustralianDiabetes,Obesity,andLifestyleStudywore
theposturebasedactivPAL3monitor[3680years(mean57.9,SD9.9years)57%womenn=698withdata].Associations
ofactivPAL3derivedmeandailytimesitting/lying(sitting),standingandsteppingwithbodymassindex(BMI),waist
circumference,bloodpressure,HbA 1c,fastingglucoseandlipids(highdensitylipoprotein,HDL,andlowdensitylipoprotein
cholesterol,total/HDLcholesterolratio,andtriglycerides),and2hplasmaglucosewereexamined.Adjustedforrelevant
confounders,sittingtostandingreallocationswereonlysignificantly(P<0.05)associatedwithapproximately2%lowerfasting
plasmaglucose,11%lowertriglycerides,6%lowertotal/HDLcholesterolratio,and0.06mmol/LhigherHDLcholesterolper2
h/day.Sittingtosteppingreallocationswereonlysignificantlyassociatedwithapproximately11%lowerBMI,7.5cmlower
waistcircumference,11%lower2hplasmaglucose,14%lowertriglycerides,and0.10mmol/LhigherHDLcholesterolper2
h/day,whilestandingtosteppingreallocationswereonlysignificantlyassociatedwith10%lowerBMI,7cmlowerwaist
circumference,and11%lower2hplasmaglucose.
ConclusionFindingssuggestedthatsittingreductionstrategiestargetingincreasedstanding,stepping,orboth,maybenefit
cardiometabolichealth.Standingisasimplealternativetositting,andrequiresfurtherexaminationinprospectiveand
interventionstudies.
Introduction

Highlevelsofsedentarytimeor,toomuchsittinghavebeenlinkeddetrimentallywithcardiovasculardisease,diabetes,and
prematuremortality. [1,2]Inmodernsociety,adultsarehighlysedentary,withtheaverageselfreportedsittingtimeranging
from3.2to6.8h/dayacross32Europeancountries[3]andobjectivemeasuresindicating5569%ofadults'wakinghoursare
spentsedentary. [4,5]Accordingly,broadlystatedguidelinesonreducingsittingtimehaveemerged. [6,7]Forthesetobecome
morespecificguidestoaction,itisimportanttounderstandtherelativebenefitsofthecommondailyactivities(standingand
stepping)thatcouldreplacesitting.Thecardiometabolichealthbenefitsofambulatoryactivityarewellestablished. [8]
However,thepotentialbenefits(orharms)ofstanding,anonambulatoryalternativetositting,arelesswellunderstood.
Experimentalstudieshaveshownacutebenefitsofstandingforpostprandialglucoseresponses, [9,10]butthereislittle
evidenceregardingnonacuterelationshipsofdirectlymeasuredstandingwithglucosemetabolismorothercardiometabolic
riskbiomarkers.Moreover,existingevidenceseldomconsiderstimedisplacementthatreducedtimespentinoneactivity
(e.g.sitting)inevitablyincreasestimespentinotheractivities(e.g.standing).Thepotentialcardiometabolicimpactofsitting
reductionsshouldincludeboththeimpactofreducingsittingtimeandofincreasingtimespentinnonsittingactivities(i.e.
standingorstepping).
Isotemporalsubstitutionaddressessuchtimedisplacements,estimatingassociationsobservedwhencrosssectionally
reallocatingtimefromoneactivitytoanother,keepingtotaltimeandtimeinotheractivitiesfixed. [11]Studiesmeasuring
activitywithhipwornaccelerometerssuggestthebenefitsofreducingsedentarytimeoncardiometabolicbiomarkerslikely
varydependingonwhatdisplacessedentarytime.Strongerassociationsareobservedwhentime(e.g.1h)isreallocatedfrom
sedentarytomoderatetovigorousintensityactivitythantolightintensityactivity. [12,13]However,isotemporalsubstitutionhas
notyetbeenusedtoexaminethepotentialhealthrelatedimpactsofreallocatingtimefromsittingtostanding.Thisis
necessarygivenrecentfindingsshowlargeshiftsbetweenthesenonambulatoryactivitiesarefeasibleandacceptable[14]but
haveanunknowncardiometabolicimpact.
Usingdatacollectedfromposturalsensors,weexaminedcrosssectionalassociationsofsitting,standing,andsteppingwith
cardiometabolicriskbiomarkersinabroadsampleofAustralianadults.Associationswereestimatedconsideringtime
displacement(isotemporalsubstitution).
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ResearchDesignandMethods
StudyDesign,Participants,andRecruitment

TheAustralianDiabetes,Obesity,andLifestyleStudy(AusDiab),ageneralpopulationbasedsampleofcommunitydwelling
Australianadultsaged25initiatedin2000,haditsthirdwaveofdatacollectionin2011/12(AusDiab3).Thisincluded
objectiveactivityassessmentinasubsampleofeligibleparticipantsrecruitedfromonsiteattendees(n=4614)from46sites
acrossAustralia. [15]Participantswereinvitedconsecutivelyuntileithernomoredeviceswereavailableorfiveparticipantshad
beenrecruitedforthatday.Atotalof1014participantswereapproachedofthese,782agreedtoweartheactivitymonitor
and741(73%)oftheseprovidedatleast1dayofvaliddata.ThestudycomplieswiththeDeclarationofHelsinki.Ethicswas
approvedbytheAlfredHealthHumanEthicsCommittee.Writteninformedconsentwasobtained.
DataCollection

Onthedayofrecruitment,aspartoftheAusDiabstudyprocedures(protocolspreviouslypublished[15,16]),participants
underwentbiochemical,anthropometric,andbehaviouralassessments.Inbrief,followinganovernightfast,astandardoral
glucosetolerancetestwasperformed,duringwhichtimeallotherdatawerecollected,andtheactivitymonitorswere
attached.
Measures

ActivityOutcomes.Activityoutcomesweremeasuredbythehighlyaccurate[1720]activPAL3activitymonitor(PAL
TechnologiesLimited,Glasgow,UKversion6.4.1seeSupplementarymaterialonline,TableS1
http://eurheartj.oxfordjournals.org/content/suppl/2015/07/28/ehv308.DC1).Themonitorwasinitialized,waterproofed,andthen
securedontotherightanteriorthighwithahypoallergenicpatch.Participantswereaskedtowearthemonitorcontinuously(24
h/day)for7daysfollowingtheonsiteassessmentandtoreportinadiaryallwakeup,sleep('lightsout'),andmonitorremoval
times(ifany).MonitordatawereprocessedinSAS9.3(SASInstituteInc.,Cary,NC,USAseeSupplementarymaterial
online,TableS1http://eurheartj.oxfordjournals.org/content/suppl/2015/07/28/ehv308.DC1).Periodsspentsleepingornot
wearingthemonitorandinvaliddayswereexcluded.Foreachparticipant,MET(metabolicequivalent)minutesofstepping
andtimespentsitting,standing,stepping,andsteppingatmoderatetovigorousintensityphysicalactivity(MVPA3METs)
weretotalledforeachday,averagedacrossvaliddays,thenintensity(METs)ofsteppingtimewascalculated(MET
minutes/minutesofstepping).
CardiometabolicandAnthropometricOutcomes.Bloodwascollectedviavenepunctureandanalysedatacentral
laboratoryinMelbourne,Victoria(HealthscopePathology).Serumtriglycerides,totalcholesterol,andhighdensitylipoprotein
(HDL)cholesterolweremeasuredbyenzymaticmethodsfastingand2hpostloadplasmaglucoseweremeasuredviaa
hexokinasemethod(SiemensAdvia2400).Lowdensitylipoprotein(LDL)cholesterolwasdeterminedusingtheFriedewald
equation. [21]Height(stadiometer)andweight(digitalscales)weremeasuredwithoutshoestothenearest0.5and0.1kg,
respectively.Bloodpressurewasmeasuredintriplicateintheseatedpositionafterrestfor5minusinganautomatedblood
pressuremonitor(DinamapProseriesMonitorModelDP101NIBP).Minimumdifferencesofinterest(per2h/dayof
activity)were:5%bodymassindex(BMI)2cmwaistcircumference5mmHgsystolicbloodpressure3mmHgdiastolic
bloodpressure10%fastingglucose,postloadglucoseandHbA1c5%total,HDL,LDLcholesterol,andtotal/HDL
cholesterolratio(equivalentto0.26mmol/Ltotalcholesterol,0.08mmol/LHDLcholesterol,and0.15mmol/LLDL
cholesterol)and10%triglycerides.
DemographicandBehaviouralAttributes.Sociodemographicandbehaviouralattributes,medicalhistory,andcurrentuse
ofantihypertensive,diabetes,andlipidloweringmedicationwereassessedviaintervieweradministeredquestionnairesand
categorizedasperSupplementarymaterialonline,Table
S2http://eurheartj.oxfordjournals.org/content/suppl/2015/07/28/ehv308.DC1.Dietaryvariableswereassessedviatheself
completedDietaryQuestionnaireforEpidemiologicalStudiesVersion2. [22]
Analysis

StatisticalanalyseswereperformedinSTATAversion12(StataCorpLP,CollegeStation,TX,USA),usinglinearizedvariance
estimation(surveycommands)toaccountfortheclusterdesignoftheAusDiabstudy.SignificancewassetatatwotailedP<
0.05andtoP<0.001forinteractions(duetotheexcessivenumberoftheseassumptiontests).Participantswhoprovidedat
leastonevaliddayofmonitordata(n=741)werenotpregnant(n=739),andwhohadcompletedataoncovariatesand
outcomes(n=698orn=664forpostloadglucose,whichwasnotassessedinthosetakingdiabetesmedications)were
included.
ThecharacteristicsofthirdwaveAusDiabattendeeswhowere/werenotincluded(duetoineligibility,samplingornon
participationSupplementarymaterialonline,Table
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S2http://eurheartj.oxfordjournals.org/content/suppl/2015/07/28/ehv308.DC1)andthebaseline(1999/2000)characteristicsof
thosewhoattended/didnotattendthethirdAusDiabwave(Supplementarymaterialonline,Table
S3http://eurheartj.oxfordjournals.org/content/suppl/2015/07/28/ehv308.DC1)werecomparedusinglogisticregression.
Associationsofactivitieswithcardiometabolicbiomarkerswereexaminedusinglinearregressionmodels.Sitting,standing,
andsteppingwereconsideredindividually,adjustingforwakingweartime(residualsmethod)andpotentialconfounders
(ModelA),andalsofurtheradjustingforMVPA(steppingat3METsModelB).Potentialconfounderswereage,gender,and
anycharacteristicthatshowedevidenceofassociationwiththeoutcome(P<0.2inbackwardeliminationSupplementary
materialonline,TableS4http://eurheartj.oxfordjournals.org/content/suppl/2015/07/28/ehv308.DC1).Whensignificant
associationswereobserved,theinterdependent(timedisplacement)associationswerethentestedusingisotemporal
substitution. [11]Associationswerereportedasregressioncoefficientsorrelativeratesforlogtransformedoutcomes,with95%
confidenceintervals,per2h/dayreallocated.Theseindicatethecrosssectionalassociationswithmeanlevelsofbiomarkers
observedwithreducingthemeantimespentinlessactivebehaviours(i.e.sittingorstanding)byequivalentlyincreasingthe
meantimespentinmoreactivebehaviours(i.e.standingorstepping)by2h/daywithoutalteringtotalwakingweartime.
Modelsreporteddidnotdisplayproblemswithnonnormality,heteroscedascicity,ornonlinearityallvarianceinflationfactors
were<2.5(Supplementarymaterialonline,TableS5
http://eurheartj.oxfordjournals.org/content/suppl/2015/07/28/ehv308.DC1).Partitionmodelsdisplayedmulticollinearity
therefore,thesewerenotreported.Sleeptime(whichhasnonlinearityissues)wasnotincludedinthemodelsonly
reallocationsbetweenwakingactivitieswereconsidered.

Results
SampleCharacteristics

Sociodemographic,behavioural,andhealthcharacteristicsofparticipantsareprovidedinSupplementarymaterialonline,
TableS2http://eurheartj.oxfordjournals.org/content/suppl/2015/07/28/ehv308.DC1.Thesamplecoveredages3680(median
=57)years,with57%women.Mostparticipantsprovidedat4daysofmonitordata(n=678,97%)andmanyprovidedall7
(n=572,82%).Onaverage(meanSD),wornwakinghours(15.71.1h/day)weremostlyspentsitting(8.81.8h/day)
andstanding(4.91.5h/day),with2.00.7hofsteppingand1.20.4hofMVPAperday.Participants'steppingintensity
wasonaverage3.110.16METs.
SelectionBias

Minor,butstatisticallysignificant,differencesbetweentheincludedsubstudyparticipants(n=698)andtheotherAusDiab
wavethreeattendees(n=3916)wereobserved(Supplementarymaterialonline,Table
S2http://eurheartj.oxfordjournals.org/content/suppl/2015/07/28/ehv308.DC1).Therewasatendencytoexcludethosewith
lowerdietaryfatintakesandthosewhowereolder,shorter,oflowersocioeconomicposition,postmenopausal,nottakingthe
oralcontraceptivepill,andwithsomepoorerhealthcharacteristics.Aspreviouslyobserved, [15]thereweresomebiasesinloss
tofollowupwithanumberofsmallbutstatisticallysignificantdifferencesinbaselinecharacteristicsbetweenthosewho
attendedthewavethreefollowupvs.thosewhodidnot(Supplementarymaterialonline,TableS3
http://eurheartj.oxfordjournals.org/content/suppl/2015/07/28/ehv308.DC1).
AssociationsofSitting,Standing,andSteppingWithCardiometabolicBiomarkers

Theassociationswithcardiometabolicbiomarkersofsitting,standing,andsteppingexaminedindividuallyareshownin.
Adjustedforconfounders,eachadditional2h/dayspentsitting(i.e.2h/daylessstandingandstepping)wassignificantly
associatedwithhigherBMI(3%withRR=1.03,95%CI:1.01,1.05),waistcircumference(=2.12,95%CI:0.83,3.41,i.e.
2cm),fastingplasmaglucose(1%),total/HDLcholesterolratio(5%),triglycerides(12%),2hplasmaglucose(4%),and
lowerHDLcholesterol(0.07mmol/L).Theassociationsofsittingwithfastingglucoseandthelipidswereindependentof
MVPA,whileassociationswiththeadipositymarkersand2hplasmaglucosewereattenuatedinmagnitudeandnolonger
statisticallysignificantfollowingMVPAadjustment.Conversely,each2h/dayspentstandingwassignificantlyassociatedwith
lowerfastingplasmaglucose(2%basedon1/RRwithRR=0.98),total/HDLcholesterolratio(6%),triglycerides(14%),
and2hplasmaglucose(3%)andhigherHDLcholesterol(0.07mmol/L).Onlytheassociationofstandingwith2hplasma
glucosewasattenuatedwithadjustmentforMVPA(to2%,P=0.104).Each2hperdayofsteppingwassignificantly
associatedwithlowerBMI(11%),waistcircumference(8cm),total/HDLcholesterolratio(6%),triglycerides(20%),and2
hplasmaglucose(14%)andhigherHDLcholesterol(0.14mmol/L).Noneoftheactivitiesshowedsignificantassociations
withsystolicanddiastolicbloodpressure,HbA 1corLDLcholesterol.Theonlyinconclusivenonsignificantfindingswerefor
associationsofstandingwithwaistcircumference,andforsteppingwithdiastolicbloodpressureandLDLcholesterol(with
confidenceintervalscontainingmeaningfulassociations,basedontheminimumdifferencesofinterest).Associationsof
sitting,standing,andsteppingwithcardiometabolicbiomarkersdidnotvarysignificantlybyageorgenderatP<0.001
(Supplementarymaterialonline,TableS6http://eurheartj.oxfordjournals.org/content/suppl/2015/07/28/ehv308.DC1).
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Table1.Associationsofobjective,posturebasedmeasuresofsitting,standing,andsteppingtimewithcardiometabolic
biomarkersinAustralianadults>35years(n=698)

Model a Sitting(2h/day)

BMI(kg/m2),RRb

Waistcircumference(cm),

SystolicBP(mmHg),

DiastolicBP(mmHg),

Fastingplasmaglucose
(mmol/L),RRb

HbA1c (mmol/mol),RRb

Total/HDLcholesterolratio,RRb

HDLcholesterol(mmol/L),

LDLcholesterol(mmol/L),

Triglycerides(mmol/L),RRb

2hpostloadglucose(mmol/L),
RRb,c

orRR(95%CI)

Standing(2h/day)
P

orRR
(95%CI)

Stepping(2h/day)
P

orRR(95%CI)

1.03(1.01,1.05)

0.002

0.98(0.96,
1.00)

0.065

0.90(0.86,0.94) <0.001

1.01(1.00,1.03)

0.142

0.99(0.97,
1.01)

0.184

2.12(0.83,3.41)

0.002

1.48(3.09,
0.13)

0.071

7.88
(10.98,4.79)

<0.001

0.92(0.39,
2.24)

0.164

0.99(2.47,
0.49)

0.183

0.76(1.87,
0.35)

0.173

0.96(0.32,
2.25)

0.136

0.75(3.01,
4.50)

0.83(2.08,
0.42)

0.185

0.94(0.38,
2.27)

0.158

0.56(0.21,
1.32)

0.151

0.49(1.45,
0.48)

0.314

1.51(3.83,
0.80)

0.42(0.49,
1.32)

0.355

0.42(1.40,
0.56)

0.390

1.01(1.00,1.03)

0.039

0.98(0.96,
1.00)

0.038

0.97(0.94,1.01)

1.02(1.00,1.03)

0.033

0.98(0.97,
1.00)

0.040

1.00(1.00,1.01) 0.350

1.00(0.99,
1.01)

0.383

0.99(0.97,1.02) 0.555

1.00(1.00,1.01)

0.371

1.00(0.99,
1.01)

0.405

1.05(1.03,1.07) <0.001

0.94(0.92,
0.96)

<0.001 0.94(0.90,0.98) 0.008

1.06(1.03,1.08) <0.001

0.94(0.92,
0.96)

<0.001

0.07
(0.10,0.04)

<0.001

0.07(0.04,
0.11)

<0.001 0.14(0.07,0.22)

0.06
(0.09,0.03)

0.001

0.07(0.03,
0.10)

<0.001

0.03(0.03,
0.08)

0.294

0.06(0.13,
0.01)

0.078

0.11(0.03,
0.25)

0.06(0.01,
0.12)

0.087

0.07(0.14,
0.00)

0.059

1.12(1.08,1.15) <0.001

0.88(0.85,
0.92)

<0.001 0.83(0.75,0.91) <0.001

1.11(1.07,1.15) <0.001

0.89(0.86,
0.93)

<0.001

1.04(1.01,1.06)

0.039

<0.001

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0.003 0.97(0.95,
1.00)

0.88(0.83,0.94)

0.689

0.193

0.142

0.001

0.119

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1.02(1.00,1.04) 0.096

0.98(0.95,
1.00)

0.104

aModelAadjustedforage,gender,andconfounders(backwardeliminationSupplementarymaterialonline,TableS4).Model

BadjustedforallvariablesinModelAandMVPA(3METs)stepping.Timespentsitting,standing,andsteppingare
adjustedforweartimeusingtheresidualsmethod.
bLogtransformedoutcomeregressioncoefficients()andconfidenceintervalsarebacktransformed,exp(),asrelativerate
(RR)with95%confidenceinterval(CI).'Nodifference'isindicatedby=0andRR=1.
cModelsexcludethoseondiabetesmedications,n=664.
Boldedvaluesindicatestatisticallysignificant(P<0.05)associations.
Theinterdependent(timedisplacement)associationswithcardiometabolicbiomarkersareshowninFigure1.Twohoursper
dayincreasesinsteppingtimeinconjunctionwithequivalentreductionsinstandingtimewereassociatedwithsignificantly
lowerBMI(10%),waistcircumference(7cm),and2hpostloadglucose(11%).Twohoursperdayincreasesinstepping
timecoincidingwithequivalentdecreasesinsittingtimeweresignificantlyassociatedwiththeseoutcomes(11%lowerBMI,
7.5cmlowerwaistcircumference,and12%lowerpostloadglucose)andwithlowertriglycerides(14%)andhigherHDL
cholesterol(0.10mmol/L).Glucoseandlipidprofileswerealsosignificantlyassociatedwithreallocatingtimefromsittingto
standing(posturechangeswithnoadditionalambulation).Each2hperdaysittingtostandingreallocationwasassociated
withsignificantlylowerfastingglucose(2%),total/HDLcholesterolratio(6%),triglycerides(11%),andhigherHDL
cholesterol(0.06mmol/L).Theonlyinconclusivenonsignificantfindingspertainedtoassociationswithwaistcircumference
ofsittingtostandingreallocationsandwithlipidoutcomesofstandingtosteppingreallocations.Furtheradjustmentfor
steppingintensitymostlydidnotalterfindings(Supplementarymaterialonline,TableS7
http://eurheartj.oxfordjournals.org/content/suppl/2015/07/28/ehv308.DC1)however,someassociationsbecamenon
significant.Mostly,thiswaswithlittleornochangestoeffectsizeexceptthatthestandingtosteppingreallocationhadan
associationwithwaistcircumferencethatchangedfrom7.0cm(P=0.001)to4.5cm(P=0.053)uponadjustment.

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Figure1.

Crosssectionalassociationswithmeancardiometabolicbiomarkersof2h/dayreductionsinmeansittingorstandingtime
coincidingwithequivalentincreasesinstandingorsteppingtime(isotemporalsubstitutionmodelsn=698or664for2hpost
loadglucose).Associationsaredescribedasregressioncoefficients()orrelativeratesforlogtransformedoutcomeswith
95%confidenceintervals,andareplottedonalogscale,withrescaledas(+mean)/mean.Modelsareadjustedforage,
gender,andconfounders(Supplementarymaterialonline,TableS4),totalweartimeandallactivitiesexcepttheonetimeis
allocatedawayfrom.Dottedlineindicatesnoassociation.ItalicisedPvaluesreportthedifferencebetweenthesitstandand
sitstepreallocations.

Discussion
Thesefindingsprovidenovelevidenceonassociationswithcardiometabolicriskbiomarkersofstanding,measuredobjectively
fromdirectposturalsensors,inasampleofAustraliancommunitydwellingadults.Importantly,associationswereidentified
withconsiderationtotimedisplacement(i.e.whensleepisnotchanged,sittingreductionsinevitablyrequireincreasesto
standingtime,steppingtime,orboth).Thesecrosssectionalfindingsprovidesomeindicationthatcardiometabolicbenefits,
particularlytoglucoseandlipidmetabolism,maybeachievedwhenreducingsittingthroughincreasesinstanding,atvolumes
showntobefeasibleandacceptableinworkplacesettinginterventions. [23,24]Significantassociationswithindicatorsof
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adiposity(BMIandwaistcircumference)wereonlyobservedwhenadditionaltimewasspentstepping(attheexpenseof
eitherreducedstandingorreducedsitting).
Akeystrengthwastheuseofhighlyaccurateactivitymonitorsthatdirectlymeasureposturefromthethighposition.Prior
studieshaveallreliedonselfreport,ormonitorswornonthehiporwaistthatarepronetomisclassification. [25]Findings
regardingthepercentageofthewakingdayspentsitting/reclining(56%),andtheassociationsofsittingtimewiththecardio
metabolicbiomarkers,werebroadlyconsistentwiththeextantliteratureonsedentarytimeasmeasuredwithothermethods.
[4,2628]Thisisoneofthefirststudiestoreportontheassociationsofobjectivelymeasuredstandingwithcardiometabolic
biomarkers.Standingcomprisednearlyonethird(31%)ofwakinghoursandmost(70%)ofthewakinghoursthatwerenot
spentsitting.Standingshowedbeneficialassociationswithlipids,andfastingand2hpostloadplasmaglucose.Theglucose
findingsareconsistentwithexperimentalstudiesshowingacutereductionsinpostprandialglucosefollowingshortboutsof
standing, [9,10]andmightbeonepathwaytoexplainthelowerriskofmortalityassociatedwithincreasedselfreported
standing. [29]MostassociationsofstandingwithcardiometabolicoutcomespersistedafteradjustmentforMVPA.However,
these'independent'or'adjusted'effectsmayunderstatetherelevanceforeachactivitytocardiometabolichealthasthey
excludeanyeffectsduetotimedisplacementmechanisms.
Weconsideredsuchtimedisplacementeffectsintheisotemporalsubstitutionanalyses.Suchapproacheshavebeenused
before, [12,13]butwithreallocationstolightintensityactivity,notspecificallybetweenseatedanduprightpostureinthe
absenceofambulation.Theassociationswithfastingglucose,HDLcholesterol,andtriglyceridesweresimilarwhether
reallocatingtimefromsittingtostanding,ortostepping:findingsconsistentwithsomeposturebasedmechanismsproposed.
Specifically,bothstandingandsteppingincreaseskeletalmuscleactivitycomparedwithasittingorrecliningposture. [30]In
animalmodels,localmusclecontractileactivityinfluencesmaintenanceoflipoproteinlipaseactivityoneofthekeyenzymes
inglucoseandlipidmetabolism. [31]Anuprightpostureisalsoassociatedwithincreasedmusclesympatheticnerveactivity[32]
andreductionsinplasmavolume, [33]whichmaycontributetotheassociationsobservedwiththelipidandglucosebiomarkers.
Theassociationwithfastingglucosewasmodestandofborderlinesignificance(P=0.047)theassociationswithlipidswere
morepronounced.
Associationswithadipositybiomarkersandpostloadplasmaglucoseappearedtodifferdependingonthespecificactivity
(standing/stepping)sittingtimewasreallocatedto.Onlythereallocationstosteppingreachedstatisticalsignificance.Theonly
inconclusivefindingwasregardingtheassociationofsittingtostandingreallocationswithwaistcircumference.These
anthropometricfindingsareconsistentwiththeknownimportanceofenergyhomeostasisforadiposity, [34]andthemuch
greaterenergyexpenditureofsteppingcomparedwithsittingorstanding[35]whichwasonaverageinthisstudy3.11METs,
1.40METs,and1.25METs,respectively.Here,2h/daysittingreductionswouldaverageincreasesof0.30METhwhen
increasingstanding,and3.72METhwhenincreasingstepping.Thoughnotmeasureddirectly,muchactivitylikelyoccurred
outsidetheexercisecontextandresultsthereforemayreflectanimportanceofnonexerciseactivitythermogenesis. [36]
Thetimedisplacementfindingswerebroadlyconsistentwiththoseofpreviousstudies. [12,13]Specifically,inadults(20
years)fromtheUSNationalHealthandNutritionExaminationSurvey,reallocatingtimefromsedentarytolightintensity
activityhadsignificantbeneficialassociationswithtriglyceridesandmarkersofinsulinresistance,withareallocationtoMVPA
necessarytoobservesignificantbeneficialassociationswithwaistcircumference. [13]Inadultsaged5779yearsfromthe
WhitehallIIepidemiologicalcohort,significantbenefitsoncardiometabolicbiomarkerswereonlyobservedwhenreallocating
timefromsedentarytoMVPA,withnostatisticallysignificantassociationsobservedforthesedentarytolightintensity
reallocation. [12]
Whileexperimentalstudiesarerequiredtoverifythesecrosssectionalfindings,theyneverthelesshaverelevanceforsitting
reductioninterventions,particularlythosethatpredominantlydisplacesittingwithonealternativeactivity.Withworkplace
treadmilldeskinterventions,sittingislikelytobereplacedpredominantlywithsteppingwithworkplacesitstandworkstation
interventions,sittingreductionsarelikelytobeprimarilyachievedbyincreasedstanding. [14]Accordingly,ifbothtypesof
interventionapproachesachieveasimilarsittingreduction,benefitstolipid(andpossiblyglucose)metabolismarelikelytobe
seeninbothinterventions,buttreadmilldeskinterventions(withtheirassociatedcaveats)maybetheapproachmostlikelyto
achievethegreatestadipositybenefits.Todate,theevidenceregardingthenonacute(i.e.>1day)effectsofsuch
interventionsonbiomarkersismostlyinconclusiveduetoinsufficientsamplesize. [37]Nonetheless,somefindingssupportthe
crosssectionalevidence.BenefitsintermsofhigherHDLcholesterolhavebeenreportedinaninterventionwhoseparticipants
mostlyorexclusivelyreplacedsittingwithstanding. [24]Conversely,benefitsforwaistcircumferenceandtotalandLDL
cholesterol[38]andweight [39]havebeenobservedininterventionswheresittingwasmostlyorexclusivelyreplacedwith
physicalactivitiesofahigherintensity(e.g.walking).
Ourstudyinvolvedamoderatesamplesizethatappearedadequatelypoweredformostanalyses,exceptforthoseinstances
whereassociationswerenonsignificantbutmeaningfuleffectsizescouldnotberuledout.Largerstudiesareneededfor
definitiveevidence.ThesamplecoveredawiderangeofcommunitydwellingadultslocatedacrossAustralia,butlossto
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followup,thesubsampling,andparticipationbiasesmaylimitgeneralizability.Keybiomarkers,includinginsulinand
inflammatorymarkers,thatmayreflectpotentialpathwaysthroughwhichsittinganduprightactivitymayimpactoncardio
metabolichealth, [40]werenotmeasured.Resultsmaybeaffectedbyresidualconfoundingfromvariablesthatwerenot
measuredormeasuredwitherror.Forexample,withlimitedmonitorremovalduringwakinghours,adjustingforwakingwear
timeindirectlycontrolledforsleep,butwithsomeresidualconfoundingpossibleduetononlinearityandmeasurementerror.
Residualconfoundingbysteppingintensityispossibleinthoseinstanceswhereadjustmentledtolossofsignificancebutthis
mayalsohavebeenpowerlossuponadjustmentasthechangestoeffectsizesweremostlylimited.Collinearityproblems
wereincurredwhenattemptingtoexamineaccumulationpatterns(prolongedvs.shorterbouts)ofsittingandstandingthat
mayhavedifferentassociationswithcardiometabolicbiomarkers [41,42]accordingly,thesewerenotreported.Longitudinalor
interventionstudiesarerequiredtoprovideevidenceregardingcausation.
Thesefindingsprovideimportantpreliminaryevidenceonthepotentialbenefitsofstandingforcardiometabolicrisk
biomarkers,especiallyimprovedlipidmetabolism.Thishasimportantpublichealthimplicationsgiventhatstandingisa
commonbehaviour, [29]themostcommonalternativetositting,andpredominantlyreplacessittinginsometypesofeffective
andacceptableenvironmentalsittingreductioninterventions. [24]Findingssuggestthatthepotentialbenefitsofsitting
reductionislikelytodependonthebehaviourswithwhichsittingisreplacedthisshouldbetestedbycomparingcardio
metabolicoutcomesfromsittingreductiontrialsthatachievecomparablesittingreductionsbyincreasedstanding(e.g.sit
standworkstationsandactivitypermissivedesks)vs.byincreasedstepping(e.g.treadmilldesks).

Sidebar
ClinicalPerspective

Standingcanbeafeasiblealternativetosittinginmanycontexts.
Cardiovascularhealthbenefitsparticularlyforglucoseandlipidmetabolismmaybeachievedbyreducingsitting
throughstanding.
Foraddressingoverweightandobesity,sittingmayneedtobereplacedwithambulatorymovement.
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Acknowledgements
WeacknowledgeandthanktheparticipantsandresearchstaffofAusDiab3.
EurHeartJ.201536(39):26432649.2015OxfordUniversityPress
Copyright2007EuropeanSocietyofCardiology.PublishedbyOxfordUniversityPress.Allrightsreserved.
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