糖尿病与发炎指标CRP

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(fēnmì)新陳代謝科第一页，共二十六页。编辑课件CRP:FromAcutePhaseProteintoCardiovasculardiseaseCRPisasymmetricalringmoleculethatconsistsof5noncovalentbutassociateprotomers.Eachprotomerhas2calciumionsresponsibleforthespecificbindingofphosphochlorine.Phosphochlorineisacommonconstituentofmanybacterialandfungalpolysaccharidesandmostbiologiccellmembranes,suchasthephosphochlorineresiduesofC(orcapsular)-polysaccharideofStreptococcuspneumoniae.Theproteinwasnamed“C-reactive”becauseofthisreaction.Astablepentamericprotein-compoundwithahalf-lifeof19hours,withoutdiurnalvariation,

CRPisapathogenicmarkerandanonspecificmarkerofinflammation.CRPissynthesizedinresponsetotheacutephaseofabacterialorfungalinfection.第二页，共二十六页。编辑课件MolecularStructureandMorphologyofHumanCRPNegativelystainedelectronmicrographshowingthetypicalpentamericdisc-likestructureface-onandside-on(arrows).Ribbondiagramofthecrystalstructure,showingthelectinfoldandthetwocalciumatoms(spheres)intheligand-bindingsiteofeachprotomer.Space-fillingmodeloftheCRPmolecule,showingasinglephosphocholinemoleculelocatedintheligand-bindingsiteofeachprotomer).PepysMB,etal.ClinInvest2003;111:1805-1812.第三页，共二十六页。编辑课件AssaysofCRPandReferenceRangesDuringtheacutephaseofinfection,serumCRPlevelsweremeasuredbyratenephelometry(“serumCRPassay”).Theseassayshavealowerlimitofdetectionofonly6to10mg/l.

Amoresensitivelatexparticle-enhancedimmunoturbidimetricassay(“highsensitivity[hs]-CRPassay”)hasbeendevelopedthathasalowerlimitofdetection(orsensitivity)ofabout0.15mg/l.Itisusedtoassessforcardiovascularrisk.Theriskfactorsbyhs-CRPlevels(CDC,AHA):CRP1mg/lislowCVDriskCRP1to3mg/lismoderateCVDriskCRP3to10mg/lishighCVDriskCRPlevels10mg/lgenerallyindicatesbacterialinfection第四页，共二十六页。编辑课件DemographicandDescriptiveCharacteristicsoftheUSPopulationWithoutaPreviousDiagnosisofHypertensionFromNHANESIIIMatthiasB.etal.DiabetesCare2004;27:1680-1687.第五页，共二十六页。编辑课件140 180mg/dLWOSCOPS:OverlapAnalysisFrequencyper100OntreatmentLDL

n Events1120 1081071 67PlaceboPravastatinRRonPravastatin=0.65Logrankp=0.002Adjustforon-treatmentLDL,HDL,VLDL,TG&baselinecovariates.RRonPravastatin=0.64,p=0.01477155116194232mg/dLWOSCOPSGroup.Circulation.1998;97:1440-45第六页，共二十六页。编辑课件

第七页，共二十六页。编辑课件TheEffectsofAtorvastatinversusSimvastatinonAtherosclerosisProgressionStudy(ASAP)AtorvastatinreducedCRPlevelstoagreaterextentthansimvastatinvanWissenS,etal.Atherosclerosis.2002;165:361-366.*P<0.001fordifferencebetweengroups;**P=0.02fordifferencebetweengroups***-50-45-40-35-30-25-20-15-10-501Year2YearsAtorvastatinSimvastatinPercentchange

inhs-CRP-44.9-14.0-40.1-19.7第八页，共二十六页。编辑课件InfluenceofBaselineBMIonAbilityofAtorvastatintoModifyCVRiskFactors(REVERSALStudy)P<0.01P<0.01P<0.05%NichollsSJ,etal.AmJCardiol2006;97:1553-7.TotalChLDL-CCRP第九页，共二十六页。编辑课件EffectsofSwitchingPravastatintoCerivastatinonC-ReactiveProtein,Butyrylcholinesterase,andLipidsPatientswereeligibleforinclusioniftheyhadanactiveprescriptionforpravastatinforatleast3months.Subjectswereconvertedfrompravastatin10mg-40mgdailytocerivastatin0.2mg-0.8mgdailyatequipotentdoses.MedianCRPlevelsatthepravastatinphase,6weeksofcerivastatin,and12weeksofcerivastatin,were0.380mg/dL,0.403mg/dL,and0.364mg/dLp=0.772),respectively.Conclusion:

MedianCRPremainedstablewithpravastatinandcerivastatinuse,althoughTCandLDLdecreased.ThefurtherdeclineobservedwithLDL,butnotCRPsuggestsdifferingeffectsofstatinsonLDLandCRP.ShinnAH,etalCurrMedResOpin.

2005;(2):207-213.第十页，共二十六页。编辑课件RiskFactorsforCHDModifiableHypertensionHighLDLcholesterolLowHDLcholesterolCigarettesmokingPhysicalinactivityDiabetesObesity(BMI>30)Thrombogenic/hemostaticstateAtherogenicdietNon-modifiableAgeMalesexFamilyhistoryofprematureCHDNationalCholesterolEducationProgramAdultTreatmentPanelIII.2002.NIHPublicationNo.02-5215.第十一页，共二十六页。编辑课件FactorsAssociatedwithIncreasedorDecreasedCRPHigherCRPHypertensionHyperglycemiaLowHDL/highTGSmokingObesityMetabolicsyndromeEstrogen/progesteroneuseChronicinfectionLowerCRPIncreaseexerciseAlcoholconsumptionWeightlossMedication:StatinFibrate第十二页，共二十六页。编辑课件HypertensionandDyslipidaemiaAreMajorRiskFactorsforCHDKannelW.In:Hypertension:PathophysiologyandTreatment.NewYork:McGraw-Hill,Inc.;1977:888-909;CastelliWP.AmJMed.1984;76:4-12.

CHDincidence/1000ProbabilityofCVD/1000Age40506070FraminghamstudySBP(mmHg)inmenTC(mg/dL)inmen第十三页，共二十六页。编辑课件ConcomitantHypertensionandDyslipidemiaIncreasetheRiskofDevelopingFatalCVDAdaptedfromDeBackerGetal.EurJCardiovascPrevRehabil.2003;10(suppl1):S1-S78.DyslipidemiaHypertensionDyslipidemia/

HypertensionTC271mg/dL

(7mmol/L)SBP180mmHgTC271mg/dL

(7mmol/L)SBP180mmHg第十四页，共二十六页。编辑课件HypertensionandHighCholesterolareTwiceasPrevalentinAdultswithDMComparedtothosewithoutDMArchivesofInternalMedicine2002;162:427-433*P<0.001第十五页，共二十六页。编辑课件HypertensionandDyslipidemiaCommonlyOccursinDiabetesinTaiwanTADE2002Prevalence(%)HighuricacidDyslipidemiaObesityHypertension第十六页，共二十六页。编辑课件C反應蛋白(dànbái)(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(bǐzhí)CRP第十七页，共二十六页。编辑课件C-RP(mg/L)01234N=1,008代謝異常數目代謝異常包括：肥胖(féipàng)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(dànbái)(CRP)與代謝異常數目InsulinResistanceAtherosclerosisStudy54321P<0.001第十八页，共二十六页。编辑课件AlbertMA,etal.Circulation.2003;107:443AlcoholConsumptionandPlasmaC-RP第十九页，共二十六页。编辑课件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

第二十页，共二十六页。编辑课件-36.4*Atorvastatin-5.2PravastatinChangeinCRPlevelsfrombaselineChange(%)*P<0.001vspravastatin-40-30-20-1001.82.918Months2.83.0BaselineAtorvastatinPravastatinCRP(mg/L)第二十一页，共二十六页。编辑课件RelationshipBetweenAdiponectinandGlycemicControl,BloodLipids,andInflammatoryMarkersinMenWithType2DiabetesMatthiasB.etal.DiabetesCare2004;27:1680-1687.BiomarkerAgeadjustedMultivariateadjusted*EstimatePEstimatePHbA1c(%)-0.160.009-0.210.001Totalcholesterol(mmol/l)0.050.2910.080.090Triglycerides(mmol/l)†-0.45<0.001-0.39<0.001HDLcholesterol(mmol/l)0.16<0.0010.13<0.001LDLcholesterol(mmol/l)0.080.0540.100.020apoB100(g/l)-0.06<0.001-0.04<0.001CRP(mg/l)-0.97<0.001-0.510.003Fibrinogen(µmol/l)-0.87<0.001-0.53<0.001sTNFR2(pg/ml)52.820.26289.770.071sICAM-1(ng/ml)-7.810.032-7.560.049sVCAM-1(ng/ml)5.790.75219.120.304第二十二页，共二十六页。编辑课件Thecorrelationmatrixamongchangesoflipidprofileandstudiedcardiovascularriskfactorsattheendof12-weekfenofibratetreatment(n=39)CorrelationΔhs-CRPΔESRΔFibrinogenΔCholΔTGΔhs-CRP1ΔESR0.7470#1ΔFibrinogen0.5449*0.8138#1ΔChol0.23550.3705∮0.27841ΔTG-0.0054-0.0077-0.13120.17541ΔHDL-c0.01000.24800.17910.0560-0.3732∮ΔUricacid-0.0107-0.1335-0.1568-0.2308-0.1788ΔCreatinine-0.2591-0.1355-0.02470.06200.0155第二十三页，共二十六页。编辑课件BegforeTXAfterTxPvalueFibrinogen(mg/dl)421152(403103)34481(33772)P<0.001ESR(mm/h)19.124.8(16.217.0)9.78.7(9.48.4)P<0.01CRP(mg/L)3.33.3(3.02.6)2.11.8(2.01.8)P<0.01Hb(g/dl)14.01.613.91.5NSProinsulin(pmol/L)45164415NSWBC(x103)7.51.97.11.7NSChangesoftheStudiedRiskFactorsattheEndof12-weekFenofibrateTreatment(n=39)第二十四页，共二十六页。编辑课件BindingandInternalizationofC-reactiveProteinbyFcgammaReceptorsonHumanAorticEndothelialCells(HAEC)MediatesBiologicalEffectsSeveralreportsshowedthatCRPbindstoFcgammareceptorsonleukocytes.CRP(100microg/mL)significantlyupregulatedsurfaceexpressionofFcgammareceptors,CD32,aswellasCD64onHAECs(P<0.01).Preincubationwit