5/14/2016

Obesityinadults:Healthhazards

OfficialreprintfromUpToDate
www.uptodate.com2016UpToDate

Obesityinadults:Healthhazards
Author
GeorgeABray,MD

SectionEditor
FXavierPiSunyer,MD,MPH

DeputyEditor
KathrynAMartin,MD

Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Apr2016.|Thistopiclastupdated:Jan02,2016.
INTRODUCTIONThemorbidityandmortalityassociatedwithbeingoverweightorobesehavebeenknown
tothemedicalprofessionformorethan2000years[1].Overweightreferstoaweightabovethenormalrange.
Thisisdeterminedbycalculatingthebodymassindex(BMI,definedastheweightinkilogramsdividedby
heightinmeterssquared).OverweightisdefinedasaBMIof25to29.9kg/m2,obesityasaBMIof>30kg/m2.
SevereobesityisdefinedasaBMI>40kg/m2(or35kg/m2inthepresenceofcomorbidities).
Thehealthhazardsassociatedwithobesityarereviewedhere.Theprevalenceofandtherapyforobesity,and
theevaluationoftheoverweightpatientarediscussedelsewhere.(See"Obesityinadults:Overviewof
management"and"Obesityinadults:Prevalence,screening,andevaluation".)
MORTALITY
EffectofBMIonmortalityIngeneral,greaterbodymassindex(BMI)isassociatedwithincreasedrateof
deathfromallcausesandfromcardiovasculardisease(CVD)(figure1).Thisisparticularlytrueforthosewith
severeobesity[2].ObesityistypicallydefinedonthebasisoftheBMI,whichismeasuredusingapatient's
weight(inkg)dividedbyheight(inm2).
Anumberoflargeepidemiologicstudieshaveevaluatedtherelationshipbetweenobesityandmortality[213].
Asanexample,ametaanalysisof97studies(2.88millionindividuals)showedthat,comparedwithnormal
weight,beingobesewasassociatedwithhigherallcausemortality(hazardratio[HR]1.18,95%CI1.121.25
forallgradesofobesitycombined)[14].Estimatesfortheannualnumberofexcessdeathsattributableto
obesityintheUnitedStatesarevariableandrangefrom111,909to365,000[15,16].
Beingoverweightalsoappearstobeassociatedwithdecreasedsurvivalinsome[5,10,17],butnotall
[12,14,18],studies.Asexamples:
AprospectivestudyfromtheUnitedStatesevaluatedtherelationshipbetweenBMIandriskofdeath
overamaximumfollowupperiodof10yearsamongover500,000menandwomenaged50to71years
[5].Amongthesubsetofindividuals50yearsofage(whenprevalenceofchronicdiseaseislow)whohad
neversmoked,anincreasedriskofdeathwasassociatedwithbeingeitheroverweight(20to50percent
increaseinthosebetween26.5to29.9kg/m2)orobese(twotooverthreefoldincreaseinthose30
kg/m2).TheriskofallcausemortalitywithincreasingBMIof25kg/m2orhigherappearstobe
independentofgenderandethnicity[5,19].
IntheProspectiveStudiesCollaborationanalysisof57prospectivestudies(894,000EuropeanandNorth
Americanadultsfollowedforameanofeightyears),mortalitywaslowestamongmenandwomenwitha
BMIbetween22.5to25kg/m2,andtherewasa30percentincreaseinoverallmortalityforeach5kg/m2
increaseinBMI(figure1)[10].
Inapooledanalysisof19prospectivestudies(1.4millionCaucasianadultswithmedianfollowupof10
years)fromtheNationalCancerInstituteCohortConsortium(NCICC),thatwasrestrictedtoparticipants
whoneversmokedanddidnothavediagnosedcancerorheartdisease,aBMIof20to24.9kg/m2was
associatedwiththelowestallcausemortality,andtherewasasimilar30percentincreaseinmortality
per5unitincreaseinBMIinthe25to49.9kg/m2range[17].
Inapooledanalysisof19prospectivecohortstudies(1.1millionAsianadultswithmeanfollowupofnine
years)fromtheAsiaCohortConsortium,thelowestriskofdeathwasamongpersonswithaBMIinthe
rangeof22.6to27.5kg/m2[20].
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Inametaanalysisof97studies(2.88millionindividuals),comparedwithnormalweight,beingoverweight
wasassociatedwithalowerallcausemortality(HR0.94,95%CI0.910.96)[14].Theseresultswere
similarafteradjustmentforsmokingstatus,preexistingdisease,andweightandheightreportingmethod
(measuredorselfreported).
Thereareanumberoffactorsthatmayhelpexplainthevariabilityintheoverweightrelatedmortalityestimates.
Variablechoiceofstatisticaltechniquesandstudypopulationsaffectestimatesofmortalityrisk[21].In
addition,BMIisaffectedbydietandexercisehabits,whichmayaffecthealth(andmortality)inwaysthatmay
bemediatedbyBMIorindependentofit.
NormalweightcentralobesityBothoverallobesity,definedbyBMI,andabdominalobesityorcentral
obesity(assessedbymeasuringwaistcircumference,waisttohipratio[WHR],orwaist/heightratio),are
associatedwithanexcessriskofCVD(see'Heartdisease'below).TheWHRisinfrequentlyusedby
cliniciansandisnotcurrentlyrecommendedaspartoftheroutineobesityevaluationbytheAmericanHeart
Association/AmericanCollegeofCardiology/ObesitySocietyguideline,althoughitwasinthepreviousversion.
DatafromtheThirdNationalHealthandNutritionExaminationSurvey(NHANESIII)suggestthatnormal
weightcentralobesity(normalBMIwithincreasedWHR)isassociatedwithhighermortalitythanBMIdefined
mortality,particularlywhencomparedtoindividualswithoutcentralobesity[22].Inacrosssectionalsurveyof
over15,000individuals,menwithanormalBMI(18.5to24.9kg/m2)butcentralobesity(WHR0.90)hadthe
highesttotalmortalityriskwhencomparedtomenwithoutcentralobesitywhowerenormalweight,overweight
(25to29.9kg/m2),orobese(30kg/m2)(HR1.87,2.24,and2.42,respectively).Normalweightwomenwith
centralobesity(WHR0.85)alsohadhighermortalityriskcomparedtonormalweightandobesewomen
withoutcentralobesity(HR1.48and1.32,respectively).Alimitationofthestudyisthatcentralobesitywas
determinedbyWHRonlynoquantitativeimagingstudiesofadiposetissuewereperformed.Thesedata
suggestthatnormalweightindividualswithcentralobesityappeartohaveanincreasedmortalityriskand
shouldbetargetedforlifestylemodificationstrategies.
MetabolicallyhealthyobesepatientsThetermmetabolicallyhealthyobeseandoverweightrefersto
individualswhodonothaveadiposityassociatedcardiometabolicabnormalities(hypertension,
hypertriglyceridemia,lowhighdensitylipoprotein[HDL]cholesterol,impairedfastingglucoseand/orevidence
ofinsulinresistance,abnormalCreactiveprotein)[23].Althoughobesepeopleareatincreasedriskforadverse
longtermoutcomesevenintheabsenceofmetabolicabnormalities,itislesscertainwhetherthisappliesto
metabolicallyhealthyoverweightindividuals.Inapooledanalysisoffourstudieswith10yearfollowup,
metabolicallyhealthyobeseindividualshadasignificantlyincreasedriskofmortalitycomparedwith
metabolicallyhealthynormalweightindividuals[13]However,inmetabolicallyhealthyoverweightindividuals,
theincreasedriskofmortalitydidnotreachstatisticalsignificance,evenwhentheanalysiswasrestrictedto
studieswithatleast10yearsoffollowup(relativerisk[RR]1.21,95%CI0.911.61).Thus,someofthe
variabilityinmortalityestimatesamongoverweightpeoplemaybeduetoinadequateadjustmentinthe
analysesforthesemetabolicfactorsorafollowupwhichistooshorttodemonstrateasignificantlyincreased
mortalityriskinoverweightmetabolicallyhealthyindividuals.
LowBMIAseparatequestionisrelatedtooutcomesinindividualswithlowerBMIvalues.Thefollowing
observationsillustratetherangeoffindingsfromvariablydefinedpatientpopulations:
IntheProspectiveStudiesCollaboration,subjectswithBMIbelow22.5kg/m2hadhighermortality
comparedwithsubjectswithaBMIof22.5to25kg/m2[10].Theexcessmortalitywaspredominantly
duetosmokingrelateddiseases(respiratoryandcancer).
IntheanalysisofstudiesfromtheNCICC,mortalityriskwassignificantlyhigheramongparticipantswith
BMIbelow22.5kg/m2(HR2.02,95%CI1.942.11forwomenwithaBMIof15to18.4comparedwith
22.5to24.9kg/m2)[17].However,theincreasedmortalityrateamongthosewithaBMIbelow22.5kg/m2
waslowerinthosewhowerehealthyandneversmokedcomparedwithallparticipants(HR1.47versus
2.02and1.37versus1.98forwomenandmen,respectively,withBMI15to18.4versus22.5to24.9kg/m
2).Inaddition,theassociationbetweenunderweightandincreasedmortalityamonghealthysubjectswho
neversmokedwasweakerafter15yearsoffollowupthanafterfiveyearsoffollowup(HRs1.21and
1.73,respectively).
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IntheAsianCohortConsortium,bothEastAsianandIndianandBangladeshipopulationswithBMIbelow
20.1kg/m2hadsignificantlyhighermortalitycomparedwithsubjectswithBMIof22.6to25kg/m2(HRs
1.84and1.59,respectively,forBMI15.1to17.5kg/m2)[20].Whentheanalysiswaslimitedto
nonsmokers,theelevatedriskwasattenuatedbutremainedsignificant(HRs1.72and1.54).
AreportfromtheNHANESdefinedunderweightasaBMI<18.5kg/m2,excludingsubjectswithillness
relatedweightloss[16].Beingunderweightwasassociatedwithexcessmortality(33,746excessdeaths)
inbothsmokersandnonsmokers[16].(See"Obesityinadults:Prevalence,screening,andevaluation",
sectionon'ClassificationofBMI'.)
Thesefindings,takentogether,suggestthattheassociationbetweenalowBMIandincreasedmortalityis
probably,inpart,anartifactofpreexistingdiseaseand/orsmoking.
CausespecificmortalityTheassociationbetweenBMIandcausespecificmortalitywasillustratedinthe
ProspectiveStudiesCollaborationanalysis[10].IntheupperBMIrange(25to50kg/m2),each5kg/m2
increaseinBMIwasassociatedwithasignificantincreaseinmortalityfromeachofthefollowingdisorders:
Ischemicheartdisease(HR1.39)andstroke(HR1.39)
Diabetes(HR2.16)andnonneoplasticchronickidneydisease(HR1.59)
Neoplasticdisease(HR1.10),withtheassociationbetweenBMIandmortalitybeingsignificantfor
severaltypesofcancer,includingliver,kidney,breast,endometrial,prostate,andcolon
Respiratorydiseases(HR1.20)
Similarfindingswerenotedforcardiovascularmortality(overallcardiovasculardisease,coronaryheartdisease
[CHD],ischemicstroke,andhemorrhagicstroke)intheAsianCohortConsortium.ComparedwithaBMIof
22.5to24.9kg/m2,EastAsianswithahigherBMIshowedadoseeffectwithasignificantlyincreasedriskof
totalcardiovasculardeath(HRs1.09,1.27,1.59,1.74,and1.97forBMIranges25to27.4,27.5to29.9,30to
32.4,32.5to34.9,and35to50,respectively)[24].EastAsianswithaBMIbelow17.5kg/m2alsohadan
increasedriskofcardiovascularmortality(HRs2.16and1.19forBMIlessthan15and15.0to17.4,
respectively).TheassociationbetweenBMIandcardiovasculardiseasemortalitywasweakerinSouthAsians
(HR1.27,95percentCI0.811.97forSouthAsianswithaBMIof35to50comparedwith22.5to24.9kg/m2).
OverweightduringadolescenceBeingoverweightduringadolescencemayalsoincreasetheriskof
prematuredeathasanadult.ThiswasillustratedinananalysisoftheNurses'HealthStudywheretheriskof
prematuredeathincreasedwithhigherBMIsatage18years.ComparedwithaBMIof18.5to21.9kg/m2at
age18years,theriskofprematuredeathsignificantlyincreasedwithaBMIgreaterthan25kg/m2(HRs1.66
and2.79foraBMIof25to29.9and30kg/m2,respectively)[25].Thisassociationcouldonlypartlybe
explainedbybeingoverweightasanadult.
TrendsincardiovascularriskfactorsTheNHANESstudyreportedthatalthoughtheprevalenceof
obesity(BMI>30kg/m2)increaseddramaticallyintheUnitedStatesbetween1960and2000(15to30
percent),theimpactofobesityonmortalitydecreasedovertime,thoughttoberelatedtomoreaggressiveand
effectivemanagementofcardiovascularriskfactors[16,26].Asexpected,therewasanincreaseindiagnosed
diabetes(1.8to5.0percent)between1960and2000thatwasmostprominentinobesesubjects(2.9to10.1
percent)[26].Incontrast,theprevalenceofothermajorcardiovascularriskfactorsdeclinedsubstantially
between1960and2000:
Serumtotalcholesterol240mg/dL(6.2mmol/L)prevalencedecreasedfrom34to17percent
Hypertension(bloodpressure140/90mmHg)31to15percent
Smoking39to26percent
Thesechangesoccurredinallweightgroups,includingobeseindividuals,andwereassociatedwithincreases
intheuseoflipidloweringdrugsandantihypertensivemedications.Asaresult,theimpactofobesityon
mortalityappearedtodecreaseovertime[16].However,theNHANESstudyalsoreportedthatthese
cardiovascularimprovementshavenotbeenaccompaniedbyreduceddisabilityintheobeseolderpopulation
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[27].Infact,obeseparticipantsweremorelikelythanthenonobesetoreportfunctionalimpairmentsovertime.
IncontrasttotheNHANESdata,inananalysisbaseduponamuchlargercohortfollowedforover20years,
therewasnoevidencethatthemagnitudeoftheassociationbetweenobesityandmortalityhaddecreasedover
time[28].
EffectoffitnessFitnesslevelisalsoanimportantfactorinobeseindividuals,asshowninametaanalysis
of10studies.Comparedtonormalweightfitindividuals,unfitindividualshadtwicetheriskofmortality
regardlessofBMI[29].Overweightandobesefitindividualshadsimilarmortalityrisksasnormalweightfit
individuals.Incontrast,intheLipidsResearchClinicsandtheNurses'HealthStudies,bothphysicalfitness
andadipositywereindependentpredictorsofmortality,andhigherlevelsofphysicalactivitydidnotnegatethe
associationbetweenobesityandmortality[30,31].
LifeexpectancyObesityinadulthoodisalsoassociatedwithastrikingreductioninlifeexpectancyforboth
menandwomen.Among3457subjectsintheFraminghamStudy,thosewhowereobese(BMI30kg/m2)at
age40yearslivedsixtosevenyearsfewerthanthosewhowerenot(BMI24.9kg/m2).Thosewhowere
overweight(BMI25to29.9km/m2)atage40yearslivedaboutthreeyearsfewer,andthosewhowereboth
obeseandsmokedlived13to14yearsfewerthannormalweightnonsmokers[32].
Asecondstudynotedasimilarreductioninlifeexpectancy,particularlyamongyoungeradults.Theimpactof
obesityonyearsoflifelost(YLL)wasgreaterformenthanwomenandforwhitesthanblacks[33].
Furthermore,inamodeldesignedtoestimatethejointeffectsofobesityandsmokingcessationonlongevity
andqualityoflifeusingdatafromNHANESI,II,III,and2004through2006,thenegativeimpactofobesityon
lifeexpectancyisforecastedtooutweighthehealthbenefitsofsmokingcessation[34].
Ithasbeensuggestedthatthesteadyriseinlifeexpectancyduringthepasttwocenturiesmaycometoanend
becauseoftheincreasingprevalenceofobesity[35].
MORBIDITYObesityandincreasedcentralfatareassociatedwithincreasedmorbidityinadditionto
mortality[36,37].InasurveyofadultsintheUnitedStates,overweightandobeseindividualshadahigher
relativeriskofhypertension,hypercholesterolemia,anddiabetesmellituscomparedwithnormalweight
individuals[38].Theriskofhypertensionanddiabetesincreasedwithincreasingbodymassindex(BMI)
(adjustedoddsratios2.6to4.8[forhypertension]and1.6to5.1[fordiabetes]inindividualswithBMIsranging
from25to40kg/m2).
IntheNurses'HealthandtheHealthProfessionalsStudies,theriskofdevelopingachronicdisease
(gallstones,hypertension,heartdisease,coloncancer,andstroke[inmenonly])increasedwithincreasing
BMI,eveninthoseintheupperhalfofthehealthyweightrange(BMI22.0to24.9kg/m2)(figure2)[39,40].
WhilethesedatasuggestthataBMI<22.0kg/m2wouldbeideal,thisisadifficultandperhapsunrealisticgoal
formanyindividuals.Inaddition,themajorityofsubjectsstudiedwereCaucasianand,therefore,thesedata
cannotbeextrapolatedtootherethnicgroups.
DiabetesmellitusType2diabetesmellitusisstronglyassociatedwithobesityinallethnicgroups.More
than80percentofcasesoftype2diabetescanbeattributedtoobesity,whichmayalsoaccountformany
diabetesrelateddeaths.
AcurvilinearrelationshipbetweenBMIandtheriskoftype2diabeteswasfoundinwomenintheNurses'
HealthStudy(figure2)[40,41].ThelowestriskwasassociatedwithaBMIbelow22kg/m2(slightlylowerthan
inmenfromtheHealthProfessionalsStudy)ataBMIgreaterthan35kg/m2,therelativeriskfordiabetes
adjustedforageincreasedto61.Theriskmaybeincreasedfurtherbyasedentarylifestyleordecreasedby
exercise(figure3)[42].(See"Riskfactorsfortype2diabetesmellitus".)
InadditiontoBMI,thedistributionofbodyfatappearstobeanimportantdeterminantofdiabetesrisk,as
illustratedbythefindingsofaprospectivepopulationbasedcohortstudyinwhich732obeseadultswere
followedforamedianofsevenyears[43].Diabetesincidenceincreasedsignificantlyacrosstertilesofbaseline
waistcircumference,waisttohipratio,andexcessvisceralfatmass,whereastherewasnoassociationnoted
betweendiabetesincidenceandtotalbodyorabdominalsubcutaneousfat[43].Similarfindingswere
previouslynotedinadultsparticipatingintheThirdNationalHealthandNutritionExaminationSurvey
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(NHANESIII),whereindividualswithhighwaistcircumferencevalues(men>102cm[40inches],women>88
cm[35inches])weremorelikelytohavediabetes,hypertension,anddyslipidemiacomparedwiththosewho
hadnormalwaistcircumferencevalues[44].
Weightgainafterage18yearsinwomenandafterage20yearsinmenalsoincreasestheriskoftype2
diabetes.TheNurses'HealthStudy,forexample,comparedwomenwithstableweight(thosewhogainedor
lost<5kg)aftertheageof18yearswithwomenwhogainedweight[40,41].Thosewhohadgained5.0to7.9
kghadarelativeriskofdiabetesof1.9thisriskincreasedto2.7forwomenwhogained8.0to10.9kg(figure
4)[40].SimilarfindingswerenotedinmenintheHealthProfessionalsStudy(figure4)[40,45].Thus,the
excessriskfordiabeteswithevenmodestweightgainissubstantial.
Weightlossisassociatedwithadecreasedriskoftype2diabetes[46].(See"Preventionoftype2diabetes
mellitus",sectionon'Weightloss/lifestyleintervention'and"Nutritionalconsiderationsintype2diabetes
mellitus".)
Theriskoftype2diabetesmayalsobeassociatedwithspecificdietarypatterns.(See"Riskfactorsfortype2
diabetesmellitus",sectionon'Dietarypatterns'.)
InsulinresistanceInsulinresistancewithhyperinsulinemiaischaracteristicofobesityandispresentbefore
theonsetofhyperglycemia.Aftertheonsetofobesity,thefirstdemonstrablechangesareimpairmentin
glucoseremovalandincreasedinsulinresistance,whichresultinhyperinsulinemia.Thehyperinsulinemiain
turnincreaseshepaticverylowdensitytriglyceridesynthesis,plasminogenactivatorinhibitor1synthesis,
sympatheticnervoussystemactivity,andsodiumreabsorption.Thesechangescontributetohyperlipidemia
andhypertensioninobesesubjects.(See"Themetabolicsyndrome(insulinresistancesyndromeorsyndrome
X)".)
Theinsulinresistancecharacteristicoftype2diabetesprobablyresultsfromacombinationofobesityand
geneticfactors.Inastudyofnondiabeticoffspringoftwoparentswithtype2diabetes,forexample,insulin
sensitivitywassimilartothatofnormalsubjectswithnofirstdegreerelativeswithtype2diabetesatnearideal
bodyweightatincreasingdegreesofobesity,however,theprogressivedecreaseininsulinsensitivitywas
muchmorepronouncedinthosewithafamilyhistoryoftype2diabetes(figure5)[47].Itisnotentirelyclear
howobesityinducesinsulinresistance,butanumberofmechanismsmaybeinvolved.(See"Pathogenesisof
type2diabetesmellitus".)
HypertensionBloodpressureisoftenincreasedinobesesubjects[38].
IntheSwedishObesityStudy,hypertensionwaspresentatbaselineinapproximatelyonehalfofsubjects
[48].
InareportfromtheNurses'HealthStudy,theBMIatage18yearsandatmidlifewaspositively
associatedwiththeoccurrenceofhypertension(figure2)[40].Weightgainwasalsoassociatedwithan
increasedrisktherelativeriskofhypertensioninthosewomenwhogained5.0to9.9kgand25.0kg
was1.7and5.2,respectively(figure4)[40].SimilarfindingswerenotedinmenintheHealth
ProfessionalsStudy(figure4)[40,45].
AreviewfromtheFraminghamHeartStudy,inwhichparticipantswereprospectivelyfollowedforupto44
years,estimatedthatexcessbodyweight(includingoverweightandobesity)couldaccountforupto26
percentofcasesofhypertensioninmenand28percentinwomen[49].
Theriskofhypertensionisgreatestinthosesubjectswithupperbodyandabdominalobesity.Themechanism
bywhichupperbodyobesityraisesbloodpressureispoorlyunderstood.Onetheoryproposesacentralrolefor
insulinresistance,leadingtoimpairedglucosetoleranceandhyperinsulinemia.Hyperinsulinemiamaythen
raisethebloodpressurebyincreasingsympatheticactivity,renalsodiumreabsorption,orvasculartone.(See
"Obesityandweightreductioninhypertension",sectionon'Hyperinsulinemiaandinsulinresistance'.)
Weightlossinobesesubjectsisassociatedwithadeclineinbloodpressure[50].Foreach1kgofweightloss,
thesystolicanddiastolicbloodpressuresfallsbyapproximately1mmHg(figure6)[51].Ontheotherhand,
persistentobesitynotonlyraisesthebloodpressuredirectly,butalsomakesthehypertensionmoredifficultto
controlbyinterferingwiththeefficacyofantihypertensivedrugs.Theeffectofweightlossinobesepatients
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withhypertensionisdiscussedingreaterdetailelsewhere.(See"Obesityandweightreductionin
hypertension",sectionon'Effectsofweightreduction'.)
DyslipidemiaObesityisassociatedwithseveraldeleteriouschangesinlipidmetabolismalthough,asnoted
above,theprevalenceofobesityassociateddyslipidemiamaybedecreasing.Unfavorableobesityrelated
effectsincludehighserumconcentrationsofcholesterol,lowdensitylipoprotein(LDL)cholesterol,verylow
densitylipoprotein(VLDL)cholesterol,andtriglycerides,andareductioninserumhighdensitylipoprotein
(HDL)cholesterolofabout5percent[52].ThelasteffectmaybemostimportantsincealowserumHDL
cholesterolconcentrationcarriesagreaterrelativeriskofcoronaryheartdisease(CHD)than
hypertriglyceridemia.
Centralfatdistributionalsoplaysanimportantroleintheserumlipidabnormalities.(See"Obesityinadults:
Prevalence,screening,andevaluation".)
GoutTheriskofdevelopinggoutyarthritisincreaseswithbodyweightandwiththeamountofweightgain
duringadulthood.TheinfluenceofBMIonhyperuricemiaandgoutisdiscussedinmoredetailelsewhere.(See
"Asymptomatichyperuricemia".)
HeartdiseaseObesityisassociatedwithanumberofriskfactorsforcardiovasculardisease,including
hypertension,insulinresistanceanddiabetesmellitus,dyslipidemia,highplasmafibrinogenconcentrationsand
otherprothromboticfactors[53],andinwomenwithcentralobesity,anincreaseinthromboxanedependent
plateletactivation[54].
Obesityisalsoassociatedwithincreasedrisksofcoronarydisease,heartfailure,andasdescribedabove,
cardiovascularandallcausemortality.Weightloss(ifachievedthroughlifestyleinterventions,medication,or
surgery)isassociatedwithanimprovementincardiovascularriskfactors[55].However,liposuctionoflarge
amountsofabdominalfatdoesnotappeartoimprovecardiovascularriskprofiles.(See"Obesity,weight
reduction,andcardiovasculardisease"and"Bariatricoperationsformanagementofobesity:Indicationsand
preoperativepreparation"and"Obesityinadults:Overviewofmanagement",sectionon'Liposuction'.)
CoronarydiseaseObesityhasbeenassociatedwithanincreasedriskofCHDandcardiovascular
mortalityinmanyobservationalstudies,includingtheFraminghamHeartStudyandtheNurses'HealthStudy
(figure2)[40,49,52].Inananalysisofpooleddatafrom97prospectivecohortstudies(1.8millionindividuals),
comparedwithnormalweight(BMI20to<25kg/m2),bothoverweight(BMI25to<30kg/m2)andobesity
(BMI30kg/m2)wereassociatedwithasignificantlyincreasedriskofCHD(hazardratio[HR]foreach5kg/m
2higherBMI1.27,95%CI1.231.31)[56].Bloodpressure,serumcholesterol,andbloodglucoseaccountedfor
approximately50percentoftheexcessriskofhighBMIforCHD.Bloodpressurewasthemostimportant
mediator,whichaccountedforapproximatelyonethirdoftheexcessrisk.
SimilarfindingswerenotedinananalysisbytheEmergingRiskFactorsCollaborationthatusedindividual
patientdatafrom58EuropeanandUnitedStatescohortstudies[57].InadultswithaBMI20kg/m2,BMI,
waistcircumference,andwaisttohipratioweresimilarlyassociatedwithcardiovascularrisk(HRforevery
standarddeviationincreaseinBMI,waistcircumference,andwaisttohipratio1.23,1.26,and1.25,
respectively).TheassociationbetweenBMI,waistcircumference,waisttohipratio,andCHDwasattenuated
(HR1.11to1.14)afteradjustmentforbloodpressure,historyofdiabetes,andtotalandHDLcholesterol.
Thedistributionofbodyfatappearstobeanimportantdeterminantaspatientswithabdominal(central)obesity
areatgreatestrisk[5861].Asanexample,intheINTERHEARTstudyofpatientsfrom52countries,
abdominalobesityaccountedfor20percentofthepopulationattributableriskofafirstmyocardialinfarction
(MI)[60,61].
Theadversecardiovasculareffectsofobesitymaybeseenatarelativelyyoungage.Asanexample,inan
autopsystudyof3000subjectsunderage35years(whohaddiedofexternalcauses),increasingBMIwas
associatedwithfattystreaksandraisedatheroscleroticlesionsintherightandleftanteriordescending
coronaryarteriesinyoungmen(butnotyoungwomen)[58].Inasecond,retrospectivestudyof189,065
patientswithacutecoronarysyndrome,increasingBMIwasassociatedwithprematureageatfirstnonST
segmentelevationmyocardialinfarction(meanage75and59yearsfortheleanest[BMI185kg/m2]and
mostobese[BMI40kg/m2]cohorts,respectively)[62].
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HeartfailureThereisanimportantassociationbetweenobesityandheartfailure.Inananalysisfrom
theFraminghamHeartStudyinwhichalmost6000individualswithoutahistoryofheartfailure(meanage55
years)werefollowedforameanof14years[63],heartfailuredevelopedin496(8.4percent).Theriskofheart
failurewasincreasedapproximatelytwofoldinobese(BMI30kg/m2)comparedwithnonobesesubjects.
Afteradjustingforestablishedriskfactors(eg,hypertension,coronarydisease,diabetes,leftventricular
hypertrophy),theriskofheartfailureincreased5percentinmenand7percentinwomenforeachincrementof
1kg/m2inBMI.Approximately11percentofcasesofheartfailureinmenand14percentinwomencouldbe
attributedtoobesityalone.Theriskwasalsoincreasedinoverweight(BMI25to29.9kg/m2)womenbutnot
men.(See"Epidemiologyandcausesofheartfailure".)
Thereareanumberofmechanismsbywhichobesitycouldpredisposetoheartfailure:
Obesityisassociatedwithseveralchangesincardiovascularfunction,someofwhichincreasecardiac
work(table1)[52,55,64].
Cardiacweightincreaseswithincreasingbodyweight:achangethatisreversible,beingproportionateto
thedegreeofweightloss[64].
Theincreasedriskofheartfailurewithobesitymaybemediatedbyinsulinresistance.Thiswas
illustratedinaprospectivecohortstudyof1187elderlymenfreeofheartfailureatbaseline.Ina
multivariateanalysisadjustedforestablishedriskfactorsforheartfailure(diabetes,priorMI,
hypertension,leftventricularhypertrophy[LVH],smoking,anddyslipidemia),independentpredictorsof
subsequentheartfailureincludedhigherBMI,waistcircumference,fastingserumproinsulinlevels,two
hourbloodglucoseconcentrations,andinsulinresistance(lowerglucosedisposalratemeasuredbya
euglycemicclampstudy).Whenglucosedisposalratewasthenaddedasacovariate,BMIandwaist
circumferencewerenolongerindependentpredictors,suggestingthatinsulinresistancemaymediatethe
increasedriskofheartfailureseenwithobesity[65].
Overweightandobesitymayalsobeassociatedwithsubclinicalrightventriculardysfunction,independentof
obstructivesleepapnea,diabetes,mellitus,andhypertension[66].
MyocardialsteatosisOnepotentialmechanismforheartdiseaseinobesityisthoughttobeexcessive
lipidaccumulationinthemyocardium.Inrodentmodels,myocardialsteatosisappearstocauseleftventricular
hypertrophyandnonischemicdilatedcardiomyopathy.Studiesinhealthysubjectsorpatientswithheartfailure
(usingmagneticresonancespectroscopy)suggestthatmyocardialtriglyceridecontentincreaseswith
increasingBMI[67].Theincreasingadiposityoftheheartmaycontributedirectlytothestructural(left
ventricularhypertrophy)andfunctional(hyperdynamiccirculation)cardiacadaptationsseenwithobesity.
ECGinmorbidobesityMorbidobesitycancausechangesincardiacmorphologythatcanalterthe
surfaceelectrocardiogram(ECG).OnestudycomparedtheECGsof100obesesubjectsand100normal
subjectsnoneofthesubjectshadanyevidenceofcardiacdisease[68].Comparedwiththenormalsubjects,
theobesesubjectshadthefollowingalterationsontheECG:
TheP,QRS,andTwaveaxesweremoreleftward
MultipleECGcriteriaforleftventricularhypertrophyandleftatrialabnormalityandTwaveflatteninginthe
inferiorandlateralleadsweremorecommon
ProlongedQTinterval(whichimproveswithweightloss)hasalsobeenreportedinobeseindividuals[69,70].
Atrialfibrillation/flutterObeseindividuals(BMI>30kg/m2)aresignificantlymorelikelytodevelopatrial
fibrillation(AF)thanthosewithanormalBMI(<25kg/m2)[7174].Thiswasillustratedinananalysisfromthe
Framinghamstudyof5282patientswithoutAFatbaseline[71].BMIwasdeterminedforallparticipants.Ata
meanfollowupof14years,526patients(10percent)developedAF.Obeseparticipants(BMI30)were
significantlymorelikelytodevelopAFthanthosewithanormalBMI(<25,adjustedHR1.52formenand1.46
forwomen).(See"Epidemiologyofandriskfactorsforatrialfibrillation".)
Inanotherpopulationbasedprospectivecohortstudyof47,589menandwomenwithoutpreexisting
cardiovasculardisease,obeseindividuals(BMI30)wereatincreasedriskfordevelopingeitheratrialfibrillation
orflutterwhencomparedwithnormalweightindividuals(BMI<25,HR2.35inmenand1.99inwomen)[72].
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TheassociationwithBMIappearstobestrongerforsustainedatrialfibrillationwhencomparedwithtransientor
intermittentatrialfibrillation[73].
StrokeObesityisassociatedwithanincreasedriskofstroke.AnanalysisbytheEmergingRiskFactors
Collaborationof21studies(over85,000participants)foundthattheriskofischemicstrokesignificantly
increasedforeveryonestandarddeviationincreaseinBMI,waistcircumference,andwaisttohipratio(HR
1.20,1.25,and1.25,respectively)[57].Afteradjustmentforage,gender,smokingstatus,bloodpressure,
historyofdiabetes,andtotalandHDLcholesterol,theriskwasmarkedlyattenuated(HR1.06to1.14).
SimilarfindingswerereportedintheGlobalBurdenofMetabolicRiskFactorsforChronicDiseases
Collaboration,ananalysisofpooleddatafrom97prospectivecohortstudies(1.8millionindividuals)[56].Both
overweightandobesitywereassociatedwithanincreasedriskofstroke(HRforeach5kg/m2higherBMI
1.18,95%CI1.141.22).Approximately75percentoftheexcessriskforstrokewasmediatedbyblood
pressure,serumcholesterol,andbloodglucose.Bloodpressurewasthemostimportantmediator,accounting
for65percentoftheexcessrisk.
DatafromtheNurses'HealthStudyandWomensHealthStudyfoundthatbothanincreasedBMI(27kg/m2)
andweightgainafterage18yearswereassociatedwithanincreasedriskofischemicstroke[75].NeitherBMI
norweightgainwasassociatedwithanincreaseintheriskofhemorrhagicstroke,althoughtherelationship
persistedfortotalstrokerisk.Inmen,increasingBMIwasassociatedwithanincreasedriskofbothischemic
andhemorrhagicstrokeinonereport[76]andwithtotalandischemic(butnothemorrhagic)inanother[77].
VenousthrombosisObesityhasbeenassociatedwithanincreasedriskofdeepveinthrombosisand
pulmonaryembolus.Thistopicisreviewedindetailelsewhere.(See"Overviewofthecausesofvenous
thrombosis",sectionon'Obesity'.)
DementiaObesitymaybeassociatedwithanincreasedriskoflaterdementia.(See"Riskfactorsfor
cognitivedeclineanddementia",sectionon'Lifestyleandactivity'.)
HepatobiliarydiseaseObesityaffectsthehepatobiliarysystem,primarilybycausingcholelithiasis.This
hasbeendemonstratedinmanystudies.IntheNurses'HealthStudy,womenwithaBMI<24kg/m2hadan
incidenceofsymptomaticgallstonesofapproximately250per100,000personyearsoffollowup[78].There
wasagradualincreaseinincidenceratewithincreasingBMI,beginningattheupperhalfofthenormalrange
(figure2)[40].SimilarfindingswerenotedinmenintheHealthProfessionalsStudy(figure2)[40].
Theincreasedriskofgallstonesinobesesubjectsisinpartexplainedbyincreasedproductionandbiliary
excretionofcholesterol.Cholesterolproductionislinearlyrelatedtobodyfatwithapproximately20mgof
additionalcholesterolbeingsynthesizeddailyforeachkgofextrabodyfat.Thus,a10kgincreaseinbodyfat
leadstothedailysynthesisoftheamountofcholesterolthatiscontainedintheyolkofoneegg.Theexcess
cholesterolisexcretedinthebile.Highbiliaryconcentrationsofcholesterolrelativetobileacidsand
phospholipidsincreasethelikelihoodofprecipitationofcholesterolwithinthegallbladder.
Weightlossmayalsoincreasethelikelihoodofcholelithiasissincethefluxofcholesterolthroughthebiliary
systemincreases.Dietswithmoderateamountsoffatthattriggergallbladdercontractionmayreducethisrisk.
Similarly,therapywithabileacid(eg,ursodeoxycholicacid)maybeadvisableinselectedsubjects(eg,
subjectswhoarelosingweightrapidly:>1to1.5kg/week).(See"Epidemiologyofandriskfactorsfor
gallstones".)
Thequantityoffatinthelivermayalsobeincreasedinobesesubjects.Steatosisisacommonabnormality
seenonliverbiopsyitisduetothedepositionoftriglyceridesinhepatocytesintheformoflipiddroplets.In
obesesubjects,excesstriglyceridesmaybeproducedduetoincreasedperipherallipolysis.Triglyceridesare
normallypackagedintoVLDLif,however,therateoftriglyceridesynthesisexceedstherateofclearance,the
excessaccumulatesintheliver.Steatosisresolveswithweightloss,exceptafterintestinalbypass.(See
"Pathogenesisofnonalcoholicfattyliverdisease".)
GERD/GIcancerObesityisariskfactorforgastroesophagealrefluxdisease(GERD),erosiveesophagitis,
esophagealadenocarcinoma,andgastriccancer.(See"Epidemiology,pathobiology,andclinicalmanifestations
ofesophagealcancer",sectionon'Obesity'and"Riskfactorsforgastriccancer",sectionon'Obesity'.)
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OsteoarthritisTheincidenceofosteoarthritisisincreasedinobesesubjectsandaccountsforamajor
componentofthecostofobesity.Osteoarthritiscommonlydevelopsinthekneesandanklesthismaybe
directlyrelatedtothetraumaassociatedwithexcessbodyweight.However,italsooccursmorefrequentlyin
nonweightbearingjoints,suggestingthattherearecomponentsoftheobesitysyndromethataltercartilage
andbonemetabolismindependentofweightbearing[79].
Inonestudyofover1000women,obesitywasclassifiedastheuppertertileofBMItheboundariesofthe
middletertilewere23.4and26.4kg/m2.Theageadjustedoddsratiosofunilateralandbilateralosteoarthritisat
theknee,determinedfromxraysoftheknees,comparingthehighandlowtertilesofBMIwere6.2and18,
respectively[80].ComparingthemiddleandlowtertilesofBMI,theoddsratiosforosteoarthritisatvarious
jointswereasfollows:

Knee2.9
Carpometacarpaljoint1.7
Distalinterphalangealjoint1.5
Proximalinterphalangealjoint1.2

Atwinstudyfoundsimilarresults:eachkilogramincreaseinbodyweight(comparedwithatwincontrol)was
associatedwithanincreasedriskofradiographicfeaturesofosteoarthritisatthekneeandcarpometacarpal
joint[81].
Conversely,weightlossisassociatedwithadecreasedriskofosteoarthritis.Inastudyof800women,a
decreaseinBMIof2kg/m2ormoreinthepreceding10yearsdecreasedtheoddsfordevelopingosteoarthritis
byover50percent[82].Thisbenefitwasalsofoundamongthosewomenwithahighriskforosteoarthritisdue
toahighbaselineBMI(25kg/m2).(See"Riskfactorsforandpossiblecausesofosteoarthritis".)
InfectionObesityisassociatedwithanincreasedsusceptibilitytoinfections,includingpostoperative,
nosocomial,andskinandsofttissueinfections[8386].Inaddition,obesepatientsaremorelikelythannormal
weightindividualstohaverespiratorycomplicationsduringinfluenzaseason[87,88].Althoughtheeffectof
obesityontheimmunesystemisnotclearlydefined,itappearstohaveaneffectindependentofcoexisting
riskfactors(eg,diabetes)[87].Asuggestedexplanationisthatobeseindividualsaremorelikelytohavelow
levelsofleptin,whichmayplayaroleintheimmuneresponse,andhighlevelsofproinflammatorycytokines
[83].(See"Physiologyofleptin",sectionon'ImmuneFunction'and"EpidemiologyofpandemicH1N1influenza
('swineinfluenza')",sectionon'Obesity'and"Treatmentofseasonalinfluenzainadults",sectionon'Definition
ofhighrisk'.)
SkinchangesSeveralchangesintheskinareassociatedwithobesity.
Stretchmarks(striae)arecommonandreflectthetensionontheskinfromexpandingsubcutaneous
depositsoffat.
Acanthosisnigricans,withdeepeningpigmentationaroundtheneck,axilla(picture1),knuckles,and
extensorsurfaces,mayoccurinconnectionwithobesity.Whilethisskinconditionhasbeenassociated
withcancerinsomepatients(eg,gastriccancer),itisnotrelatedtoanincreasedriskofcancerinobese
subjects.Theproposedcauseofthislesionissustainedhyperinsulinemia[89].(See"Insulinresistance:
Definitionandclinicalspectrum".)
Hirsutisminwomenmayresultfromincreasedproductionoftestosterone,whichisoftenassociatedwith
visceralobesity.(See"Pathogenesisandcausesofhirsutism".)
RespiratorysystemSleepapneaisthemostimportantrespiratoryproblemassociatedwithobesityand
diabetes[90],withseveralstudiesconfirmingthatobesityisamajorriskfactorforthedevelopmentof
obstructivesleepapnea.(See"Clinicalpresentationanddiagnosisofobstructivesleepapneainadults"and
"Obstructivesleepapneaandcardiovasculardisease".)
Otheralterationsinpulmonaryfunctionmayoccur,includinghigherresiduallungvolumeassociatedwith
increasedabdominalpressureonthediaphragm,decreasedlungcomplianceandincreasedchestwall
impedance,ventilationperfusionabnormalities,reducedstrengthandenduranceofrespiratorymuscles,
depressedventilatorydrive[91],andbronchospasm(asthma).(See"Pathogenesisofobesityhypoventilation
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syndrome".)
Obesityhasbeenthoughttobeariskfactorforasthma[92,93],butinonecohortstudy,obesitywas
associatedwithdyspneabutnotasthma[94](see"Riskfactorsforasthma",sectionon'Obesity').These
effectsonrespiratoryfunctionareconsideredtoberelativelybenignoruncommon,comparedwiththe
problemsinducedbyobesityassociatedhypoventilationorobstructivesleepapnea.
CancerCertainformsofcanceroccurwithincreasedfrequencyinobesemenandwomen[9597].Obesity
alsoincreasesthelikelihoodofdyingfromcancer.Inametaanalysisof141studiesthatincluded282,137
cancercases,a5kg/m2increaseinBMIinmenwasassociatedwithesophageal,thyroid,colon,andrenal
cancers(RR1.52,1.33,1.24,and1.24,respectively)[98].Inwomen,a5kg/m2increasewasassociatedwith
endometrial,gallbladder,esophageal,andrenalcancers(RR1.59,1.59,1.51,and1.34,respectively).
AssociationsweresimilarinstudiesfromNorthAmerica,Europe,Australia,andtheAsiaPacificregion,with
theexceptionofstrongerassociationsbetweenBMIandbreastcancerintheAsiaPacificpopulations.
InasubsequentcohortstudywithprospectivelycollecteddatafromtheUnitedKingdomClinicalPractice
ResearchDatalink,5.24millionadultswithoutapreviouscancerdiagnosiswerefollowedtoinvestigatethe
associationbetweenBMIand22ofthemostcommoncancers[99].Duringtheobservationperiod(7.5years),
166,955individualsdevelopedoneofthecancers.Forsomecancers,therewasalinearassociationandfor
others,anonlinearassociationwithsubstantialvariationduetoindividualcharacteristics(gender,age,
menopausalstatus,smoking).HighBMIwasassociatedwithanincreasedriskofthefollowingcancers:

Endometrial
Gallbladder
Kidney
Liver
Colon
Cervical
Thyroid
Ovarian
Postmenopausalbreast
Leukemia

Overweightandobesitywereestimatedtoaccountforbetween2(thyroid)and41(endometrial)percentof
thesecancers.
Therelationshipbetweenobesityandriskofbreast,endometrial,colon,andprostatecancerarereviewed
separately.(See"Factorsthatmodifybreastcancerriskinwomen"and"Endometrialcarcinoma:Epidemiology
andriskfactors",sectionon'Obesity'and"Riskfactorsforprostatecancer",sectionon'Obesity'and
"Colorectalcancer:Epidemiology,riskfactors,andprotectivefactors",sectionon'Obesity'.)
EndocrinechangesInadditiontothechangesnotedabove(diabetesandhyperlipidemia),severalother
endocrinechangesareassociatedwithobesity.Irregularmensesandanovulatorycyclesarecommoninobese
women,andfertilitymaybedecreased.Therearealsoreportsofanincreasedriskofpregnancyinduced
hypertension,andcesareandeliverymaybemorefrequent.(See"Theimpactofobesityonfemalefertilityand
pregnancy".)
Disordersofsexualarousalandorgasmmaybemorecommoninoverweightandobesewomen[100].(See
"Sexualdysfunctioninwomen:Epidemiology,riskfactors,andevaluation".)
Inmen,obesityisanindependentriskfactorforerectiledysfunction.(See"Overviewofmalesexual
dysfunction".)
KidneydiseaseObesityisassociatedwithmultipleotherconditionsthatareknowntocausecompromised
renalfunction,includinghypertension,diabetes,andthemetabolicsyndrome.However,datafromthe
FraminghamOffspringstudy,theHypertensionDetectionandFollowUpProgram,andtheMultiphasicHealth
TestingServicesProgramsuggestthatobesitymaybeindependentlyassociatedwiththeriskofdeveloping
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chronickidneydisease[101104].Focalsegmentalglomerulosclerosisandobesityrelatedglomerulopathy
(glomerularenlargementandmesangialexpansion),bothofwhichareassociatedwithproteinuria,havebeen
describedinpatientswithsevereobesity.Obesityrelatedglomerulopathymaybereversiblewithweightloss.
(See"Epidemiologyofchronickidneydisease"and"Secondaryfactorsandprogressionofchronickidney
disease"and"Epidemiology,classification,andpathogenesisoffocalsegmentalglomerulosclerosis".)
KidneystonesObesityandweightgainduringadulthoodappeartobeassociatedwithanincreasedrisk
ofkidneystones[105].(See"Riskfactorsforcalciumstonesinadults".)
UrinaryincontinenceInwomen,overweightandobesityareimportantriskfactorsforurinaryincontinence.
(See"Evaluationofwomenwithurinaryincontinence",sectionon'Riskfactors'.)
PsychosocialfunctionObesesubjectsareoftenexposedtopublicdisapprovalbecauseoftheirfatness.
Thisstigmaisseenineducation,employment,andhealthcare,amongotherareas.Inastudyofover10,000
adolescents,womenwhowereoverweight(definedasaBMIabovethe95thpercentileforageandsex)
completedfeweryearsofschool(0.3yearless),werelesslikelytobemarried(20percentlesslikely),had
lowerhouseholdincomes($6710lessperyear),andhadhigherratesofhouseholdpoverty(10percenthigher)
thanthewomenwhohadnotbeenoverweight,independentoftheirbaselinesocioeconomicstatusand
aptitudetestscores[106].Menwhohadbeenoverweightwerelesslikelytobemarried(11percentlesslikely).
Depressionhasalsobeenseeninassociationwithsevereobesity,particularlyinyoungerpatientsandin
women[107].
COSTOFOBESITYIntheSwedishObesityStudy,obesesubjectshad1.4to2.4timesthenumberof
daysofsickleavethandidnormalweightsubjectsandwere1.5to2.8timesaslikelytodrawadisability
pension.Inaddition,yearlydrugcostsweresignificantlyhigherinobesecomparedwithnormalweightpeople
[108].Surgicaltreatmentforobesitylowereddiabetesandcardiovasculardiseaserelateddrugcostsbut
increasedgastrointestinaldrugcosts,resultinginsimilartotaldrugcostsforsurgicallyandconventionally
treatedobesepatients.(See"Bariatricoperationsformanagementofobesity:Indicationsandpreoperative
preparation".)
Otherreportshavefoundanincreaseinhealthcareexpendituresamongoverweightsubjects[37,109112].In
onestudy,subjectsattheextremesofbodymassindex(BMI)hadthehighestexpenditures,whilethoseinthe
middleoftheBMIrange(26to27kg/m2)hadthelowestprobabilityofusinghealthcaredollars.Inasecond
reviewofover17,000peopleinahealthmaintenanceorganization,therewasanassociationbetweenBMIand
annualratesofoutpatientvisitsandinpatientdays,annualcostofoutpatientvisits,costsofoutpatient
pharmacyandlaboratoryservices,andtotalcostofcare(bothinpatientandoutpatient)[110].
Specifically,meanannualtotalcostswere25percentgreateramongsubjectswithaBMI30to34.9kg/m2
relativetoaBMIof20to24.9kg/m2and44percentgreateramongthosewithaBMIof35kg/m2orhigher.
Thehighercostswerepredominantlyexplainedbythepresenceofcoronaryheartdisease(CHD),
hypertension,anddiabetes.SimilardatahavebeenpresentedintheNetherlandsandFrance.
INFORMATIONFORPATIENTSUpToDateofferstwotypesofpatienteducationmaterials,TheBasics
andBeyondtheBasics.TheBasicspatienteducationpiecesarewritteninplainlanguage,atthe5thto6th
gradereadinglevel,andtheyanswerthefourorfivekeyquestionsapatientmighthaveaboutagiven
condition.Thesearticlesarebestforpatientswhowantageneraloverviewandwhoprefershort,easytoread
materials.BeyondtheBasicspatienteducationpiecesarelonger,moresophisticated,andmoredetailed.
Thesearticlesarewrittenatthe10thto12thgradereadinglevelandarebestforpatientswhowantindepth
informationandarecomfortablewithsomemedicaljargon.
Herearethepatienteducationarticlesthatarerelevanttothistopic.Weencourageyoutoprintoremailthese
topicstoyourpatients.(Youcanalsolocatepatienteducationarticlesonavarietyofsubjectsbysearchingon
patientinfoandthekeyword(s)ofinterest.)
Basicstopics(see"Patientinformation:Weightlosstreatments(TheBasics)"and"Patientinformation:
Healthrisksofobesity(TheBasics)")
BeyondtheBasicstopics(see"Patientinformation:Weightlosstreatments(BeyondtheBasics)"and
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"Patientinformation:Weightlosssurgeryandprocedures(BeyondtheBasics)")
SUMMARY
Obesityisassociatedwithsignificantexcessmorbidityandmortality.Estimatesforannualobesity
associatedmortalityareextremelyvariable.(See'Mortality'above.)
Obesityandincreasedcentralfatareassociatedwithincreasedmorbidity,includingdiabetesmellitus,
hypertension,heartdisease,stroke,sleepapnea,andmanyothers.Weightlosswillimprovemostof
thesemorbidities.(See'Morbidity'above.)
Themanagementofobesityisdiscussedindetailelsewhere.(See"Obesityinadults:Overviewof
management".)
UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.
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GRAPHICS
AllcausemortalityversusBMIforeachsexintherange15to50
kg/m 2(excludingthefirstfiveyearsoffollowup)

Relativerisksatage35to89years,adjustedforageatrisk,smoking,andstudy,were
multipliedbyacommonfactor(ie,floated)tomaketheweightedaveragematchthePSC
mortalityrateatages35to79years.Floatedmortalityratesshownaboveeachsquare
andnumbersofdeathsbelow.Areaofsquareisinverselyproportionaltothevarianceof
thelogrisk.BoundariesofBMIgroupsareindicatedbytickmarks.95%CIsforfloated
ratesreflectuncertaintyinthelogriskforeachsinglerate.Dottedverticallineindicates
25kg/m 2 (boundarybetweenupperandlowerBMIrangesinthisreport).Above25
kg/m 2 ,mortalitywasonaverageapproximately30percenthigherforevery5kg/m 2
higherBMI.
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BMI:bodymassindexPSC:ProspectiveStudiesCollaboration.
Reproducedwithpermissionfrom:WhitlockG,LewingtonS,SherlikerP,etal.Bodymassindexand
causespecificmortalityin900,000adults:collaborativeanalysesof57prospectivestudies.Lancet
2009373:1083.IllustrationusedwiththepermissionofElsevierInc.Allrightsreserved.
Graphic73156Version4.0

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Bodymassindexandtheriskofdisease

Increasingbodymassindex(BMIkg/m 2 ),evenwithinthenormal
rangeofBMI(21to24.9),isassociatedwithanincreasedriskoftype
2diabetes,hypertension,coronaryheartdisease,andcholelithiasis.
PanelAshowsdataforwomenintheNurses'HealthStudy,initially30
to55yearsofage,whowerefollowedforupto18years.PanelB
showsdataformenintheHealthProfessionalsFollowupStudy,
initially40to65yearsofage,whowerefollowedforupto10years.
Datafrom:WillettWC,DietzWH,ColditzGA.Guidelinesforhealthyweight.N
EnglJMed1999341:427.
Graphic76866Version4.0

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Importanceofbodyweightandexerciseondevelopmentof
type2diabetes

Adjustedincidenceoftype2diabetesmellitusin5990meninrelationtoBMI(in
kg/m 2 )andthelevelofphysicalactivity(inkcal/week).Theriskoftype2
diabeteswasdirectlyrelatedtoBMI,whileregularexercisewasprotectiveexcept
forinmenwithaBMIbelow24.
BMI:bodymassindex.
Datafrom:HelmrichSP,RaglandDR,LeungRW,PaffenbargerRSJr.Physicalactivityand
reducedoccurrenceofnoninsulindependentdiabetesmellitus.NEnglJMed1991
325:147.
Graphic79316Version4.0

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Adultweightchangeandtheriskofdisease

Evenamodestincreaseinweightasanadultisassociatedwithan
increasedriskoftype2diabetes,hypertension,coronaryheart
disease,andcholelithiasis.PanelAshowsdataforwomeninthe
Nurses'HealthStudy,initially30to55yearsofage,whowere
followedforupto18years.PanelBshowsdataformenintheHealth
ProfessionalsFollowupStudy,initially40to65yearsofage,who
werefollowedforupto10years.
Datafrom:WillettWC,DietzWH,ColditzGA.Guidelinesforhealthyweight.N
EnglJMed1999341:427.
Graphic52842Version2.0

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Obesitydecreasesinsulinsensitivityinsusceptible
subjects

Responsivenesstoinsulin(asassessedfromtheintravenousglucose
tolerancetest)accordingtobodyweightinnondiabeticsubjectswith
nofamilyhistoryoftype2diabetesmellitusinfirstdegreerelatives
andinthosewithtwoparentswithtype2diabetes.Bothgroupshad
similarinsulinresponsivenessatnearnormalidealbodyweight,but
thedegreeofinsulinresistance(decreaseininsulinsensitivity)as
bodyweightincreasedwasmorepronouncedintheoffspringof
parentswithtype2diabetes.
Datafrom:KahnCR.BantingLecture.Insulinaction,diabetogenes,andthe
causeoftypeIIdiabetes.Diabetes199443:1066.
Graphic70645Version2.0

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Weightlossinducedreductionindiastolicblood
pressure

Relationshipbetweenthequantityofweightlostandthefallindiastolic
bloodpressurein308moderatelyobesepatientsgivenaweight
reductionregimenfor18months.Thepatientsbeganwithadiastolic
pressurebetween80and89mmHgthosewholostthemostweighthad
thelargestreductionindiastolicpressure.Thedecreasesinthesystolic
pressureweresimilar.
BP:bloodpressure.
Datafrom:StevensVJ,CorriganSA,ObarzanekE,etal.Weightlossintervention
inphase1oftheTrialsofHypertensionPrevention.TheTOHPCollaborative
ResearchGroup.ArchInternMed1993153:849.
Graphic60178Version6.0

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Comparisonofcardiacstructuralandhemodynamicalterationsin
patientswithmorbidobesityandhypertension

Obesity
alone

Hypertension
alone

Obesityand
hypertension

Variable
Heartrate

Normal

Normal

Normal

Bloodpressure

Normal

Increased

Increased

Strokevolume

Increased

Normal

Increased

Cardiacoutput

Increased

Normal

Increased

Systemicvascular

Decreased

Increased

Normalorincreased

LVvolume

Increased

Normal

Increased

LVwallstress

Normalor

Normalorincreased

Increased

resistance

increased
LVhypertrophy

Eccentric

Concentric

Hybrid

LVdiastolic

Usuallypresent

Usuallypresent

Usuallypresent

LVsystolic

Occasionally

Usuallyabsent

Occasionallypresent

dysfunction

present

LVfailure

Occasionally

Occasionallypresent

Commonlypresent

Usuallyabsent

Occasionallypresent

dysfunction

present
RVhypertrophy

Occasionally
present

RVenlargement

Occasionally
present

Usuallyabsent

Occasionallypresent

RVfailure

Occasionally

Usuallyabsent

Occasionallypresent

present
LV:leftventricularRV:rightventricular.
Adaptedfrom:AlpertMA,HashimiMW.Obesityandtheheart.AmJMedSci1993306:117.
Graphic74883Version3.0

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Acanthosisnigricans

Classichyperpigmentedaxillarylesioninacanthosisnigricans.
CourtesyofJeffreyFlier,MD.
Graphic53776Version3.0

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ContributorDisclosures
GeorgeABray,MDSpeaker'sBureau:Takeda[Obesity(NaltrexoneHCl/bupropionHCl)].
Consultant/AdvisoryBoards:Herbalife[Obesity(Nutritionandweightmanagementproducts)]Janssen
Pharmaceuticals[Obesity(Weightlossprogram)]NovoNordisk[Obesity(Liraglutide)].FXavierPiSunyer,
MD,MPHConsultant/AdvisoryBoards:EliLilly[Diabetes(Newinsulins)]McNeilNutritionals[Diabetes,
obesity(Sucralose)]NovoNordisk[Diabetes,obesity(Liraglutide)]Zafgen[Obesity(Newdrugs)].KathrynA
Martin,MDNothingtodisclose.
Contributordisclosuresarereviewedforconflictsofinterestbytheeditorialgroup.Whenfound,theseare
addressedbyvettingthroughamultilevelreviewprocess,andthroughrequirementsforreferencestobe
providedtosupportthecontent.Appropriatelyreferencedcontentisrequiredofallauthorsandmustconformto
UpToDatestandardsofevidence.
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