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InternationalJournalofObesity(2008)32,S1–S22008NaturePublishingGroupAllrightsreserved0307-0565/08$30.
00www.
nature.
com/ijoPLENARYLECTUREST1:PLWillthehumangenomegiveustheanswertoobesityAdebate–thecasefor.
PFroguelMD,PhD,GenomicMedicine,HammersmithHospital,ImperialCollegeLondon,UKandCNRS8090-InstituteofBiology,PasteurInstitute,Lille,FranceObesityhasbeenconsideredaparadigmformanyofthecommonchronicnoncommunicablehumandiseasesoftheglobalization,whichgenerallyresultwhenmultipleinheritedsusceptibilityvariantsinteractwiththe'Westernised'environmenttomodulatediseasepredisposition.
Recentlargescaletwinstudiesconfirmedtheimportantroleofinheritedfactorsinthedevelopmentofobesity.
Furthermore,anonnegligiblefractionofearlyonsetsevereobesitycasescarryDNAdefectsinasinglegeneresultingindramaticallyimpairedappetiteregulation.
These(ratherunexpected)discoverieshavegreatlyimprovedourunderstandingoftheroleontheenergybalanceoftheleptin-melanocortinpathwayinhumans.
RecentanalysesoftheimpactofMC4-Rnonsynonymousmissensemutationsinlargepopulationshaveshownthatbothlackandgainoffunctionexist,leadingtoeithersevereobesityorasignificantprotectionagainstoverweight.
However,eveninthismodeltheenvironmentmaymodulatetheobesityphenotype.
Polygenicobesitygeneticsisstillpoorlyunderstoodbutpastandon-goinggenomewidestudiesbringnewharvestofgenesandlocithathavebeenproventoincreasetheriskforobesity.
Inthisregard,therecentdiscoveriesoffrequentDNAvariants(SNPs)inthehypothalamusexpressedFatmassandObesityassociatedFTOandProconvertase1(PCSK1)genesandintheMC4-Rregulatoryregionevidencethatproteinsinvolvedinfoodintakebehaviourregulationareindeedcontributingtothedevelopmentofobesityinhumans.
ApartfromfrequentSNPs,itislikelythatmanyraremutations,copynumbervariationandepigeneticfactorsinthesegenesandinothersmayparticipatetoobesitypathophysiology.
TheemergingpictureofobesitymolecularmechanismincludesdifferentgeneticmechanismsincludingallelicselectionintheNeolithicage,theaccumulationofpathogenicraremutations,aswellasthestrongeffectofrecentobesegenicpressureon"thriftygenes"ancestralalleles.
Elucidatinggeneticeffectsshouldnotonlybringnovelandunsuspectedhypothesesbutwillalsosupportepidemiologicalstudiesinordertodifferentiateetiologicalandconfoundingfactors.
WillthehumangenomegiveustheanswertoobesityAdebate–andthecaseagainst.
HeitmannBLInstituteofPreventiveMedicine,CentreforHealthandsociety,CopenhagenDenmarkObesityisunderstronggeneticinfluence.
AdoptionstudiesshowthatadultbodymassindexamongadopteesishighlycorrelatedwithBMIofbiologicalparentsbutnotofadoptiveparents.
Inaddition,twinstudiesalsoshowthatgeneticpredispositiontoobesityaccountsformostofthefamilialcorrelationinobesityandabdominalfatdistribution.
Suchstudiessuggestthatthehumangenomeplaysanessentialroleforobesity.
However,environmentalinfluencesalsoplayaroleandinteractwiththegeneticpredispositiontoproduceobesity,andtheindividualdifferencesinobesitydevelopmentsuggestthatnotallvariationinobesitycanbeattributedtothegenes.
Also,theverylargedifferencesseenamongsocialclassesintheoccurrenceofobesity,withprevalences5timeshigheramonggroupswithlowcomparedtohighsocioeconomicstatus,suggestthatthegeneticpredispositionismodifiable.
Itisarguedthatobesityisageneticdiseaseexpressedonlywhentheenvironmentsupportsitsoccurrenceandcognitivesuperstructuresarenotoperating,andthatthehumangenomewillnotgiveustheanswertoobesity.
T2:PLFor:HowUsefulareClinicalGuidelinesforWeightManagementLeanMEJUniversityofGlasgowandUniversityofOtagoDatingfrom1996(SIGN),obesityguidelinesintegratetreatment(weightloss,avoidinggain,optimalrisk-factormanagement)withprevention,withinhealthcareservices,population-directedhealth-promotionandmodifyingobesogenicfood-,physical-,educational-andfiscal-environments.
Towarrantaguideline,animportanthealthproblemisperceivedassuboptimallyorinconsistentlymanaged,withneedtoprotectpatientsfromhazardousorineffectivetreatments,orfromfailure-to-treatwhenevidenceispositive.
Commonly,treatmentsarenotdirectlycomparablewithinpatients(egdiet,drugs,surgery)andhead-to-headtrialslacking,soguidelinestaketheformofalgorithms.
Preventionguidelinesoftenlackexperimentalorevengoodobservationaldatabutaimtohelppolicy-makersfromanunderstandingofunderlyingscientificprincipleswhenmuchmisinformationiscirculatingandresourcesscarce.
Methodologiestoproduceconvincingevidence-basesoftenlagbehindneedforguidance,sotheirfirst'usefulness'isineducatingtheirexpertwritersandcommissioningagencies.
Obesityguidelineshavenotyetgeneratedreducedprevalence,orsecondarydiseases.
Thisaspirationwasinappropriate,astime-coursesfrompublicationtochangingpracticearelong,andthediseaseevenlonger.
Usefulnesscanbegaugedearlierfromacademiccitations–egc.
150forSIGN1996,frommentionswithinotherclinicalguidelines(egCHD,diabetes,venousthrombosis,asthma,arthritis).
Secondarycareconsultantsnowagreetomanageobesitywithinc.
30%ofdiversespecialties.
About70%ofGPsandnursesreadtheSIGNobesityguideline,anditsrecommendationtorecordheight/weightnowformsnormalpractice.
Governmentpublic-healthstrategieshavebeeninformedbySIGNclinicalguidelines,callsforactionbeingstrengthenedbyconsistencyofsimilarguidelinesinternationally.
Against:HowusefulareclinicalguidelinesforobesitymanagementMercerSWUniversityofGlasgow,Glasgow,Scotland,UKObesityisgloballyregardedasamajorpublichealthissue.
Chronicdiseasemanagementinmanycountries,includingtheUK,isincreasinglybeingdeliveredinprimarycareusingprotocolsbasedonclinicalguidelines.
WhynotaddobesitytothegrowinglistofconditionsnowbeingtreatedbysuchanapproachAlthoughsuperficiallyattractive,thereareanumberofreasonstobelievethatrelyingsolelyonclinicalguidelinesforobesitymanagementisdoomedtofailure.
Firstly,despitedecadesofresearch,theevidence-baseforeffectiveandpracticalinterventionsforobesityisperhapssurprisinglysomewhatlimited,andthequalityandbreadthofstudiesusedtodevelopguidelinesequallylimited.
Morefundamentally,the'gold-standard'ofclinicalguidelineevidence-base,therandomisedcontrolledtrial,producesevidencebasedonoftenhighlyselectedsub-groupsofpatientswhichisthusofunknownrelevancetothebulkofthepopulationwiththetargetcondition.
Secondly,systematicreviewssuggestthattheissuingofclinicalguidelinesoftenfailstochangepractice.
Thirdly,themanagementofcomplexconditionssuchasobesityrequirescomplexinterventions,underpinnedbytheorythatembracessuchcomplexity,whichfurthermitigatesagainsttheusefulnessofsimpleguidelines.
Obesitymanagementisalsoinfluencedbyahugerangeofimportanthuman,system,andenvironmentalfactors.
Noclinicalguidelinecanleadpatientanddoctorthroughthelabyrinthofdecisionsthatneedtobemadeinprioritisingandtargetingwhichproblemtoaddressfirstandhow–onlyindividualisedcare,clinicalwisdomandshareddecisionsbasedontherapeuticrelationshipscantacklesuchcomplexity.
AbstractsS2InternationalJournalofObesityT3:PLWhyaclusterisreallyacluster:insulinresistanceandcardiovasculardiseaseReaven,GStanfordUniversitySchoolofMedicineThreesetsofdiagnosticcriteriahavebeenproposedtoidentifyindividualswithwhathasbeentermedthemetabolicsyndrome(MetS):WHO,ATPIII,andtheIDF.
Thegoalistoidentifyindividualsatincreasedcardiovasculardisease(CVD)risk,andthesamecomponentsareusedtomakethediagnosis.
However,thethreeorganizationsdifferintheirapproachtodiagnosingtheMetS.
TheWHOrequiresthatevidenceofinsulinresistancebepresentinordertomakeadiagnosis,whereastheAmericanHeartAssociationandtheNationalHeart,Lung,andBloodInstitute,focusedontheATPIIIcriteria,statethattheMetS"istrulyasyndrome,i.
e.
,agroupingofASCVDriskfactors,butonethatprobablyhasmorethanonecause.
"Incontrast,theIDFstatesthat"centralobesity,asassessedbywaistcircumferencewasagreedasessential"tothediagnosis,basedon"thelikelihoodthatcentralobesityisanearlystepintheetiologicalcascadeleadingtothefullmetabolicsyndrome.
"QuestionshavebeenraisedastotheclinicalutilityofdiagnosingtheMetS,regardlessoftheversionused.
However,ratherthanaddressthisissue,apathophysiologicalapproachwillbetaken,andthefocuswillbeonwhythespecificcomponentsusedinallversionsformaclusterofrelatedCVDriskfactors.
Morespecifically,evidencewillbepresentedthatinsulinresistance,andhowtheorganismrespondstothisdefect,providestheonlycoherentexplanationastowhytheabnormalitiesthatcomprisethecurrentversionsoftheMetSclustertogether.
T4:PLEnvironmentalandcognitivedeterminantsofenergybalance-relatedbehavioursKremers,SPJMaastrichtUniversity,Maastricht,TheNetherlandsStudiesondeterminantsofenergybalance-relatedbehaviourshaveoftenusedisolatedapproaches.
Forexample,theyareeitherbasedonsocial-cognitivemodelsofhealthbehaviourortheyapplyanecologicalapproach.
Anoverviewwillbepresentedofthecurrentempiricalbaseregardingenvironmentalandsocial-cognitivedeterminantsofenergybalance-relatedbehaviours.
Inthispresentation,itisarguedthattheoriginsofenergybalance-relatedbehavioursnecessitateanintegratedapproachinthestudyofbehaviouraldeterminants.
SuchanintegratedapproachisconceptualizedintheEnRGframework(EnvironmentalResearchframeworkforweightGainprevention).
Intheframework,behaviourispostulatedtobetheresultofasimultaneousinfluenceofconsciousandunconsciousprocesses.
'Obesogenic'environmentalinfluencesarehypothesisedtoinfluencebehaviourbothindirectlyanddirectly.
Theindirectcausalmechanismreflectsthemediatingroleofbehaviour-specificcognitionsintheinfluenceoftheenvironmentonbehaviour.
Adirectinfluencereflectstheautomatic,unconscious,influenceoftheenvironmentonbehaviour.
Specificpersonalandbehaviouralfactorsarepostulatedtomoderatethecausalpath(i.
e.
,inducingeithertheautomaticorthecognitivelymediatedenvironment–behaviourrelation).
Exampleswillbepresentedregardingthepotentialadditionalvalueofapplyinganintegratedapproach.
Itmayguideresearchtowardscausalmechanismslinkingspecificenvironmentalfeatureswithenergybalance-relatedbehavioursindistinctpopulations.
Futureperspectivesarediscussedintermsoftheevolutionofaparadigmthatmayhelptodisentangletheroleof'obesogenic'environmentalfactors.
T5:PLHowtoputthebrakesontheobesityepidemicSwinburnBAWHOCollaboratingCentreforObesityPrevention,DeakinUniversity,Melbourne,AustraliaItissurprisingthatatanindividualandpopulationlevel,obesityisnotonlypersistentbutincreasingdespitetheapparentlypowerfulbrakesofsufficientknowledgeaboutcausesandsolutions,strongsocialprejudiceagainstobesity,personallossofqualityoflife,andevenphysiologicalresponsesagainstweightgain.
Highlyobesogenicenvironmentsbackedbystrongcommercialdriversandviciouscycleswhichtrappeopleintheobesestatehelptoexplainthisparadox.
Asocietalapproachwillbeneededtoreducetheobesityepidemicandinparticulartocurtailthecommercialdriversofoverconsumption(especiallyovereatingandcardependence).
Thiswillrequirepoliticalleadershipandapolicybackbonetosupporton-the-groundprogramsandsocialmarketing.
Unfortunately,theinitialpoliticalresponsesinternationallyhavebeentoimplementtheprograms(ofteneducational)withoutthepolicy.
Policyoptions,includingregulationsrestrictingfoodmarketingtochildrenandchangingfoodsupplypoliciesandrelatedfiscaldrivers,willbeveryimportant.
Community-basedprogramscanpotentiallycreatetheirown'epidemics'ofhealthyeatingandphysicalactivityastheytakeownershipoftheproblemandteacheachotheraboutcreatingsolutions.
Itislikelythatmanyofthesolutionsforobesitywillcomefromactiontotackleothersocietalissueswithclimatechange,trafficcongestion,andurbanliveabilitybeingthemostlikelysourcesof'stealth'interventionsforobesity.
Therearefewexamplesinternationallyofreversalsofobesity,butitislikelythathigherincome,youngerwomeninwealthycountrieswillbethefirstsub-populationtoshowreductionsinobesityprevalence.