糖尿病与发炎指标CRPppt课件

.,1,糖尿病與發炎指標CRP,吳達仁醫師成大醫學院附設醫院內科部內分泌新陳代謝科,.,2,CRP:FromAcutePhaseProteintoCardiovasculardisease,CRPisasymmetricalringmoleculethatconsistsof5noncovalentbutassociateprotomers.Eachprotomerhas2calciumionsresponsibleforthespecificbindingofphosphochlorine.Phosphochlorineisacommonconstituentofmanybacterialandfungalpolysaccharidesandmostbiologiccellmembranes,suchasthephosphochlorineresiduesofC(orcapsular)-polysaccharideofStreptococcuspneumoniae.Theproteinwasnamed“C-reactive”becauseofthisreaction.Astablepentamericprotein-compoundwithahalf-lifeof19hours,withoutdiurnalvariation,CRPisapathogenicmarkerandanonspecificmarkerofinflammation.CRPissynthesizedinresponsetotheacutephaseofabacterialorfungalinfection.,.,3,MolecularStructureandMorphologyofHumanCRP,Negativelystainedelectronmicrographshowingthetypicalpentamericdisc-likestructureface-onandside-on(arrows).Ribbondiagramofthecrystalstructure,showingthelectinfoldandthetwocalciumatoms(spheres)intheligand-bindingsiteofeachprotomer.Space-fillingmodeloftheCRPmolecule,showingasinglephosphocholinemoleculelocatedintheligand-bindingsiteofeachprotomer).,PepysMB,etal.ClinInvest2003;111:1805-1812.,.,4,AssaysofCRPandReferenceRanges,Duringtheacutephaseofinfection,serumCRPlevelsweremeasuredbyratenephelometry(“serumCRPassay”).Theseassayshavealowerlimitofdetectionofonly6to10mg/l.Amoresensitivelatexparticle-enhancedimmunoturbidimetricassay(“highsensitivityhs-CRPassay”)hasbeendevelopedthathasalowerlimitofdetection(orsensitivity)ofabout0.15mg/l.Itisusedtoassessforcardiovascularrisk.Theriskfactorsbyhs-CRPlevels(CDC,AHA):CRP1mg/lislowCVDriskCRP1to3mg/lismoderateCVDriskCRP3to10mg/lishighCVDriskCRPlevels10mg/lgenerallyindicatesbacterialinfection,.,5,DemographicandDescriptiveCharacteristicsoftheUSPopulationWithoutaPreviousDiagnosisofHypertensionFromNHANESIII,MatthiasB.etal.DiabetesCare2004;27:1680-1687.,.,6,WOSCOPS:OverlapAnalysis,Frequencyper100,OntreatmentLDL,WOSCOPSGroup.Circulation.1998;97:1440-45,.,7,.,8,TheEffectsofAtorvastatinversusSimvastatinonAtherosclerosisProgressionStudy(ASAP),AtorvastatinreducedCRPlevelstoagreaterextentthansimvastatin,vanWissenS,etal.Atherosclerosis.2002;165:361-366.,*P0.001fordifferencebetweengroups;*P=0.02fordifferencebetweengroups,*,*,-50,-45,-40,-35,-30,-25,-20,-15,-10,-5,0,1Year,2Years,Atorvastatin,Simvastatin,Percentchangeinhs-CRP,-44.9,-14.0,-40.1,-19.7,.,9,InfluenceofBaselineBMIonAbilityofAtorvastatintoModifyCVRiskFactors(REVERSALStudy),P0.01,P0.01,P30)Thrombogenic/hemostaticstateAtherogenicdiet,Non-modifiableAgeMalesexFamilyhistoryofprematureCHD,NationalCholesterolEducationProgramAdultTreatmentPanelIII.2002.NIHPublicationNo.02-5215.,.,12,FactorsAssociatedwithIncreasedorDecreasedCRP,HigherCRPHypertensionHyperglycemiaLowHDL/highTGSmokingObesityMetabolicsyndromeEstrogen/progesteroneuseChronicinfection,LowerCRPIncreaseexerciseAlcoholconsumptionWeightlossMedication:StatinFibrate,.,13,HypertensionandDyslipidaemiaAreMajorRiskFactorsforCHD,KannelW.In:Hypertension:PathophysiologyandTreatment.NewYork:McGraw-Hill,Inc.;1977:888-909;CastelliWP.AmJMed.1984;76:4-12.,CHDincidence/1000,ProbabilityofCVD/1000,Age,40,50,60,70,Framinghamstudy,SBP(mmHg)inmen,TC(mg/dL)inmen,.,14,ConcomitantHypertensionandDyslipidemiaIncreasetheRiskofDevelopingFatalCVD,AdaptedfromDeBackerGetal.EurJCardiovascPrevRehabil.2003;10(suppl1):S1-S78.,Dyslipidemia,Hypertension,Dyslipidemia/Hypertension,TC271mg/dL(7mmol/L),SBP180mmHg,TC271mg/dL(7mmol/L)SBP180mmHg,.,15,HypertensionandHighCholesterolareTwiceasPrevalentinAdultswithDMComparedtothosewithoutDM,ArchivesofInternalMedicine2002;162:427-433,*P0.001,.,16,HypertensionandDyslipidemiaCommonlyOccursinDiabetesinTaiwan,TADE2002,Prevalence(%),Highuricacid,Dyslipidemia,Obesity,Hypertension,.,17,C反應蛋白(CRP)可加強TC/HDL比值預估首度心肌梗塞發生之風險,RidkorPM.Circulation1996;97:2007-11.,冠心病風險,TC/HDL比值,CRP,.,18,C-RP(mg/L),01234,N=1,008,代謝異常數目,代謝異常包括：肥胖高血壓高三酸甘油脂症低HDL-C高胰島素血症,Festaetal.Circulation2000;102:42-7.,C反應蛋白(CRP)與代謝異常數目InsulinResistanceAtherosclerosisStudy,54321,P0.001,.,19,AlbertMA,etal.Circulation.2003;107:443,AlcoholConsumptionandPlasmaC-RP,.,20,ManyAssaysDevelopedBeforehs-CRPAreMoreSensitiveThan“hs-CRPAssay”,Asearlyas1981,asolid-phasesingle-antibodycompetitiveradioimmunoassaywithasinglerabbitanti-CRPantibodydirectlyimmobilizedontoamagneticparticlehadasensitivityof0.05mg/l.Withuseofadouble-antibodycompetitiveradioimmunoassay,thesensitivitywasincreasedfurtherto0.003mg/l.Anin-houseELISACRPassaydevelopedin1997hasasensitivityof0.007mg/landwasusedin1999toevaluatethehs-CRPtestforclinicaluse.In2000,animmunoradiometricassay(IRMA)wasdevelopedwithpolyclonalantibodiesofCRPimmobilizedonmicrotiterplatesandmonoclonalantibodiesofCRPlabeledwith125I.IRMAhadasensitivityof0.05mg/l,.,21,-36.4*,Atorvastatin,-5.2,Pravastatin,ChangeinCRPlevelsfrombaseline,Change(%),*P0.001vspravastatin,-40,-30,-20,-10,0,1.8,2.9,18Months,2.8,3.0,Baseline,Atorvastatin,Pravastatin,CRP(mg/L),.,22,RelationshipBetweenAdiponectinandGlycemicControl,BloodLipids,andInflammatoryMarkersinMenWithType2Diabetes,MatthiasB.etal.DiabetesCare2004;27:1680-1687.,.,23,Thecorrelationmatrixamongchangesoflipidprofileandstudiedcardiovascularriskfactorsattheendof12-weekfenofibratetreatment(n=39),.,24,ChangesoftheStudiedRiskFactorsattheEndof12-weekFenofibrateTreatment(n=39),.,25,BindingandInternalizationofC-reactiveProteinbyFcgammaReceptorsonHumanAorticEndothelialCells(HAEC)MediatesBiologicalEffects,SeveralreportsshowedthatCRPbindstoFcgammareceptorsonleukocytes.CRP(100microg/mL)significantlyupregulatedsurfaceexpressionofFcgammareceptors,CD32,aswellasCD64onHAECs(P0.01).Preincubationwithanti-CD32andCD64antibodiessignificantlyinhibitedmaximalbindingof