Therelationshipbetweeninsulin-sensitiveobesityandcardiovascular
diseasesinaChinesepopulation
ResultsoftheREACTIONstudy
JieliLua,b,1,2,YufangBia,b,1,2,TiangeWanga,b,1,2,WeiqingWanga,b,2,YimingMuc,2,JiajunZhaod,2,ChaoLiue,2,
LuluChen
f,2,LixinShig,2,QiangLih,2,QinWani,2,ShengliWuj,2,GuijunQink,2,TaoYangl,2,LiYanm,2
,
YanLiun,2,GuixiaWangn,2,ZuojieLuoo,2,XuleiTangp,2,GangChenq,2,YananHuor,2,ZhengnanGaos,2,
QingSu
t,2,ZhenYeu,2,YoumingWangv,2,HuacongDengw,2,XuefengYux,2,FeixiaSheny,2,LiChenz,2
,
LiebingZhaoa,b,2,MengDaia,b,2,MinXua,b,2,YuXua,b,2,YuhongChena,b,2,ShenghanLaiaa,2,GuangNing
a,b,⁎,2
a
KeyLaboratoryforEndocrineandMetabolicDiseasesofMinistryofHealth,Rui-JinHospital,ShanghaiJiao-TongUniversitySchoolofMedicine,E-InstituteofShanghaiUniversities,China
b
ShanghaiClinicalCenterforEndocrineandMetabolicDiseases,NationalClinicalResearchCenter,DepartmentofEndocrineandMetabolicDiseases,RuiJinHospital,
ShanghaiJiaoTongUniversitySchoolofMedicine,China
c
People'sLiberationArmyGeneralHospital,China
d
ShandongProvincialHospital,China
e
JiangsuProvinceHospitalonintegrationofChineseandWesternMedicine,China
f
WuhanXieheHospital,HuazhongUniversityofScienceandTechnologySchoolofMedicine,China
g
UniversityofGuizhouSchoolofMedicine,China
h
UniversityofHaerbinSchoolofMedicine,China
i
UniversityofLuzhouSchoolofMedicine,China
j
XinjiangKelamayiPeoplesHospital,China
k
UniversityofZhengzhouSchoolofMedicine,China
l
UniversityofNanjingSchoolofMedicine,China
m
UniversityofZhongshanSchoolofMedicine,China
n
UniversityofJilinSchoolofMedicine,China
o
UniversityofGuangxiSchoolofMedicine,China
p
UniversityofLanzhouSchoolofMedicine,China
q
UniversityofFujianSchoolofMedicine,China
r
JiangxiPeople'sHospital,China
s
UniversityofDalianSchoolofMedicine,China
t
XinhuaHospital,ShanghaiJiaoTongUniversitySchoolofMedicine,China
u
ZhejiangCenterforDiseaseControlandPrevention,China
v
UniversityofAnhuiSchoolofMedicine,China
w
UniversityofChongqingSchoolofMedicine,China
x
WuhanTongjiHospital,China
y
WenzhouUniversitySchoolofMedicine,China
z
QiluHospital,UniversityofShandongSchoolofMedicine,China
aa
JohnsHopkinsUniversitySchoolofMedicine,Baltimore,UnitedStates
InternationalJournalofCardiology172(2014)388–394
⁎Correspondingauthorat:ShanghaiClinicalCenterforEndocrineandMetabolicDiseases,NationalClinicalResearchCenter,DepartmentofEndocrineandMetabolicDiseases,RuiJin
Hospital,ShanghaiJiaoTongUniversitySchoolofMedicine,197Rui-Jin2ndRoad,Shanghai200025,China.Tel.:+862164370045x665340;fax:+862164373514.
E-mailaddress:gning@sibs.ac.cn(G.Ning).
1
Contributedequallytothisarticle.
2
Allauthorstakeresponsibilityforallaspectsofthereliabilityandfreedomfrombiasofthedatapresentedandtheirdiscussedinterpretation.
0167-5273/$–seefrontmatter©2014ElsevierIrelandLtd.Allrightsreserved.
http://dx.doi.org/10.1016/j.ijcard.2014.01.073
ContentslistsavailableatScienceDirect
InternationalJournalofCardiology
journalhomepage:www.elsevier.com/locate/ijcard
abstractarticleinfo
Articlehistory:
Received23December2013
Accepted18January2014
Availableonline25January2014
Keywords:
Insulinresistance
Obesity
Cardiovasculardiseases
Epidemiology
Objective:Obesityandinsulinresistanceareriskfactorsforcardiovasculardiseases.Whetherinsulin-sensitive
obeseindividualsareathigherriskforcardiovasculardiseasesisstilldebated.Weaimtoinvestigatewhether
insulin-sensitiveobesityassociateswithprevalentcardiovasculardiseasesand10-yearcoronaryheartdisease
(CHD)risk.
Researchdesignandmethods:AtthebaselineoftheRiskEvaluationofcAncersinChinesediabeTicIndividuals:a
lONgitudinal(REACTION)study,211,641participantsaged40yearsorolderwererecruitedfrom25communi-
tiesacrosstheChinamainland,in2011to2012.Participantswerecategorizedbyinsulin-sensitive/resistantand
general/abdominalobesestatus.CardiovasculardiseasesincludedCHD,stroke,andmyocardialinfarction.Fra-
minghamriskscore(FRS)wascalculatedaccordingtoNationalCholesterolEducationProgram-AdultTreatment
PanelIIIandFRSgreaterthan20%orcardiovasculardiseaseswereidentifiedashighriskfor10-yearCHD.
Results:Controllingforpotentialconfounders,comparedwithinsulin-sensitivenormalweightindividuals,
insulin-sensitivegeneralobeseindividualshadincreasedrisksforprevalentcardiovasculardiseases(men:OR,
2.55,95%CI,2.04–3.18;women:1.73,1.45–2.06)and10-yearFraminghamriskforCHD(men:2.26,1.86–
2.76;women:1.73,1.46–2.06).Comparedwithinsulin-sensitivenormalwaistsubgroup,insulin-sensitiveab-
dominalobesitywasassociatedwithhigherrisksforprevalentcardiovasculardiseases(men:1.32,1.20–1.46;
women:1.36,1.27–1.47)and10-yearFraminghamriskforCHD(men,1.34,1.23–1.45;women,1.37,1.27–1.47).
Conclusion:Bothgeneralandabdominalobesitywereassociatedwithelevatedprevalentcardiovasculardiseases
and10-yearCHDrisk,regardlessofthepresenceorabsenceofinsulinresistance.
©2014ElsevierIrelandLtd.Allrightsreserved.
1.Introduction
Obesityisawell-recognizedhealthhazardandhasconsistentlybeen
associatedwithsubstantialexcessrisksformorbidityandmortality,
especiallyfromcardiovasculardiseases[1–3].Asubsetofobeseindivid-
ualsisknownasmetabolicallyhealthyobese(MHO),whichwascharac-
terizedbyanexcessivebodyfatcoupledwithabenignmetabolicprofile,
suchasfavorableinsulinsensitivity,soundlipids,nosignofhypertension
andinflammation,andnormalhormonalprofiles[4–6].Theseindividuals
seemtodeviatefromthedevelopmentofobesity-relatedmetabolicab-
normalities[7–9],however,severalstudiesrevealedinconsistentviews
thatMHOindividualswerestillatriskofmajorcardiovasculardiseases
comparedwithhealthynonobese[10,11].
Insulinresistanceisacorefeatureofmetabolicdisordersandusually
coexistswithobesityinsomehumans[12,13].Butasubgroupofobese
individualsdisplaysbetterinsulinsensitivitycomparedtothatofnormal
weightindividuals,andthisphenotypewasdescribedasinsulin-sensitive
obesity[14].Untilrecently,themetabolicprofileofthisphenotypeinthe
generalpopulationvarieswidelyamongdifferentstudypopulations.
Previousstudiesthathaveexaminedtheobesity-relatedcomplications
ininsulin-sensitiveobeseindividualshaveconflictingresults[7,9,11,15].
Epidemiologicaldataontherelationshipbetweeninsulin-sensitiveobesi-
tyandcardiovasculardiseasesarerareinChinesepopulation.Giventhat
Asianshaveauniquephenotypecharacterizedbyrelativelyhighabdom-
inalobesityandtendtohavehighprevalenceofcardiovascularriskfac-
torsevenatlowbodymassindex(BMI)[16–19],wehypothesizethat
bothgeneralandabdominalobesityareriskfactorsforcardiovascular
diseasesindependentofinsulinresistance,andinsulin-sensitiveobesity
couldalsotakeresponsibilityforhighcardiovascularrisk.Inthisstudy,
weinvestigatetheassociationbetweeninsulin-sensitiveobesityandcar-
diovasculardiseasesinChinesepopulation.
2.Researchdesignandmethods
2.1.Studypopulation
TheRiskEvaluationofcAncersinChinesediabeTicIndividuals:alONgitudinal(REAC-
TION)studyhasbeensetupasamulticenterprospectiveobservationalstudyaimingto
evaluatethechronicdiseasesinChinesepopulation[20,21].Theoveralldesignofthe
REACTIONstudyincludedtwophases:thebaselineandfollow-up.Thepresentstudypre-
sentedthebaselinedata.Atbaseline,in2011to2012,atotalof259,657individualsaged
40yearsorolderwererecruitedfrom25researchcentersacrossChina.Theseresearch
centerswereselectedfrombothruralandurbanareasofdifferentgeographicregions,
withdifferentdegreesofurbanizationandeconomicdevelopmentstatus,andrepresented
thegeneralmiddle-agedandelderlypopulationofChina.Amongthe25communities,
233,736participantsfrom24communitiesconductedinsulindetermination.Participants
meetingthefollowingcriteriawereexcluded:1)thosewithoutcompletedatatodefinein-
sulinresistanceandobesity(n=4967)and2)thosewhowerereceivingantidiabetic
treatment(n=17,128).Atotalof211,641participantswereincludedinthefinalanalysis.
TheREACTIONstudyissponsoredbytheChineseSocietyofEndocrinologyandledby
Rui-JinHospitalaffiliatedtoShanghaiJiao-TongUniversitySchoolofMedicine.Allproce-
duresusedinthisstudywereinaccordancewithinstitutionalguidelines.TheCommittee
onHumanResearchatRuiJinHospital,ShanghaiJiaoTongUniversitySchoolofMedicine,
approvedthestudyprotocol,andallstudyparticipantsprovidedwritteninformed
consents.
2.2.Datacollection
Ateachstudysite,trainedstaffcollecteddataaccordingtoastandardprotocolinex-
aminationcentersatlocalhealthstationsorcommunityclinicsintheparticipants'resi-
dentialarea.Usingastandardquestionnaireandface-to-faceinterviews,thestaff
collectedinformationonsociodemographiccharacteristics,lifestylefactors,medicalhisto-
ryandfamilyhistory.Educationattainmentsweredividedintohighschooleducationor
aboveif9yearsofelementaryorsecondaryeducationwerecompleted,andlessthan
highschooliflessthan9yearsofelementaryorsecondaryeducation.Participantswere
definedasnever,former,orcurrentsmokersaccordingtocigarettesmokinghabits.The
typeandfrequencyofalcoholconsumptionswererecorded,andnever,formerorcurrent
alcoholdrinkingstatuswasdefinedaccordingtoalcoholconsumptionhabits.TheGlobal
PhysicalActivityQuestionnairewasusedtoestimatephysicalactivitiesduringwork,
transportation,andleisuretimebycollectingintensity,duration,andfrequencyofphysical
activity.Themetabolicequivalentminutesperweek(MET-min/week)wasusedtomea-
surephysicalactivities[22].Clinicalexaminationsofweight,height,waistcircumference
andbloodpressuresweremeasuredaccordingtoastandardprotocolandperformedby
experiencednurses.BMIwascalculatedasbodyweightinkilogramsdividedbybody
heightsquaredinmeters(kg/m
2
).Anautomatedelectronicdevice(OMRONModel
HEM-725FUZZY,OmronCompany,Dalian,China)wasusedtomeasuresystolicblood
pressure(SBP)anddiastolicbloodpressure(DBP)inthenon-dominantarmofseatedpar-
ticipantsthreetimesconsecutivelyat1-minintervalsaftera≥5-minrest.Thelasttwo
readingswereaveragedforanalysis.TheFraminghamriskscore(FRS)wascalculatedac-
cordingtotheNationalCholesterolEducationProgram-AdultTreatmentPanelIIIalgorithm,
basedoncoronaryriskfactorsincludingage,sex,totalcholesterol,high-densitylipoprotein
cholesterol(HDL-C),SBP,andsmokinghabit[23].Amongtheseriskfactors,age,totalcholes-
terol,HDL-CandSBPlevelswerecategorizedaccordingtotheirvaluesandsmokingwasclas-
sifiedaseither“currentsmoker”or“non-smoker”.Thecalculatedtotalscoreswereusedto
estimatethe10-yearcoronaryheartdisease(CHD)risk.
2.3.Biochemicalevaluation
Bloodsampleswerecollectedafteranovernightfastforatleast10h.Self-reported
historyofdiabeteswasconfirmedbyclinicalrecords,orbytheuseofinsulinorhypogly-
cemicagents.Participantswithoutaknownhistoryofdiabetesunderwenttheoralglucose
tolerancetest,andplasmaglucosewasobtainedat0and2hduringthetest.Bloodspec-
imenswereprocessedatthefieldcenterswithChinaNationalLaboratoryAccreditation.
Plasmaglucoseconcentrationswereevaluatedatlocalhospitalsbymeansoftheglucose
389J.Luetal./InternationalJournalofCardiology172(2014)388–394
