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,

LuluChenf,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,

QingSut,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,GuangNinga,b,⁎,2

aKeyLaboratoryforEndocrineandMetabolicDiseasesofMinistryofHealth,Rui-JinHospital,ShanghaiJiao-TongUniversitySchoolofMedicine,E-InstituteofShanghaiUniversities,ChinabShanghaiClinicalCenterforEndocrineandMetabolicDiseases,NationalClinicalResearchCenter,DepartmentofEndocrineandMetabolicDiseases,RuiJinHospital,

ShanghaiJiaoTongUniversitySchoolofMedicine,ChinacPeople'sLiberationArmyGeneralHospital,ChinadShandongProvincialHospital,ChinaeJiangsuProvinceHospitalonintegrationofChineseandWesternMedicine,ChinafWuhanXieheHospital,HuazhongUniversityofScienceandTechnologySchoolofMedicine,ChinagUniversityofGuizhouSchoolofMedicine,ChinahUniversityofHaerbinSchoolofMedicine,ChinaiUniversityofLuzhouSchoolofMedicine,ChinajXinjiangKelamayiPeoplesHospital,ChinakUniversityofZhengzhouSchoolofMedicine,ChinalUniversityofNanjingSchoolofMedicine,ChinamUniversityofZhongshanSchoolofMedicine,ChinanUniversityofJilinSchoolofMedicine,ChinaoUniversityofGuangxiSchoolofMedicine,ChinapUniversityofLanzhouSchoolofMedicine,ChinaqUniversityofFujianSchoolofMedicine,ChinarJiangxiPeople'sHospital,ChinasUniversityofDalianSchoolofMedicine,ChinatXinhuaHospital,ShanghaiJiaoTongUniversitySchoolofMedicine,ChinauZhejiangCenterforDiseaseControlandPrevention,ChinavUniversityofAnhuiSchoolofMedicine,ChinawUniversityofChongqingSchoolofMedicine,ChinaxWuhanTongjiHospital,ChinayWenzhouUniversitySchoolofMedicine,ChinazQiluHospital,UniversityofShandongSchoolofMedicine,ChinaaaJohnsHopkinsUniversitySchoolofMedicine,Baltimore,United

StatesInternationalJournalofCardiology172(2014)388–394

⁎Correspondingauthorat:ShanghaiClinicalCenterforEndocrineandMetabolicDiseases,NationalClinicalResearchCenter,DepartmentofEndocrineandMetabolicDiseases,RuiJinHospital,ShanghaiJiaoTongUniversitySchoolofMedicine,197Rui-Jin2ndRoad,Shanghai200025,China.Tel.:+862164370045x665340;fax:+862164373514.

E-mailaddress:gning@sibs.ac.cn(G.Ning).1Contributedequallytothisarticle.2Allauthorstakeresponsibilityforallaspectsofthereliabilityandfreedomfrombiasofthedatapresentedandtheirdiscussed

interpretation.

0167-5273/$–seefrontmatter©2014ElsevierIrelandLtd.Allrightsreserved.

http://dx.doi.org/10.1016/j.ijcard.2014.01.073ContentslistsavailableatScienceDirect

InternationalJournalofCardiology

journalhomepage:www.elsevier.com/locate/ijcardabstractarticleinfo

Articlehistory:

Received23December2013

Accepted18January2014

Availableonline25January2014

Keywords:

Insulinresistance

Obesity

Cardiovasculardiseases

EpidemiologyObjective: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,andrepresentedthegeneralmiddle-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/m2).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.

Plasmaglucoseconcentrationswereevaluatedatlocalhospitalsbymeansoftheglucose389J.Luetal./InternationalJournalofCardiology172(2014)388–394