糖尿病肾脏病病人的血糖控制精品课件.ppt

糖尿病肾脏病病人的血糖控制,1,.,大纲,目前已经存在的在糖尿病肾脏病病人中的血糖控制效果的证据肾功能基本正常的1和2型糖尿病病人透析前的病人HD和PD的病人目前已经建议的糖尿病肾脏病病人血糖控制的方法降糖药物的治疗胰岛素治疗可能的研究领域,2,IntensivetreatmentofhyperglycemiapreventsDKDandmayslowtheprogressionofestablishedkidneydisease,LoweringHbA1clevelstoapproximately7.0%reducesthedevelopmentofmicroalbuminuria.(Strong)LoweringHbA1clevelstoapproximately7.0%reducesthedevelopmentofmacroalbuminuria.(Moderate)LoweringHbA1clevelstoapproximately7.0%reducestherateofdecreaseinGFR.(Weak),KDOQIClinicalPracticeGuidelinesandClinicalPracticeRecommendationsforDiabetesandChronicKidneyDisease:AmJKidneyDis49:S1-S180,2007(suppl2),3,4,EffectofGlycemicControlonKidneyFunctionandAlbuminuriainType1Diabetes,5,TheDiabetesControlandComplicationsTrial:DCCT,Studydesign:amulticenter，randomizedclinicaltrialParticipants：1441patientswithtype1diabetesGroup:primary-preventioncohort：726withnoretinopathysecondary-interventioncohort：715withmildretinopathyIntervention：intensivetherapy：administeredeitherwithanexternalinsulinpumporbythreeormoredailyinsulininjectionsandguidedbyfrequentbloodglucosemonitoringconventionaltherapy：oneortwodailyinsulininjectionsFollowedforameanof6.5yearsMainOutcomeMeasures:appearanceandprogressionofretinopathyandothercomplications,6,DCCT-MeasurementsofGlycosylatedHemoglobinandBloodGlucoseinPatientswithIDDMReceivingIntensiveorConventionalTherapy,TheDiabetesControlandComplicationsTrialResearchGroup:Theeffectofintensivetreatmentofdiabetesonthedevelopmentandprogressionoflong-termcomplicationsininsulin-dependentdiabetesmellitus.NEnglJMed329:977-986,1993,7,DCCT,56%,43%,34%,TheDiabetesControlandComplicationsTrialResearchGroup:Theeffectofintensivetreatmentofdiabetesonthedevelopmentandprogressionoflong-termcomplicationsininsulin-dependentdiabetesmellitus.NEnglJMed329:977-986,1993,primary-preventioncohort,secondary-interventioncohort,8,TheEpidemiologyofDiabetesInterventionsandComplications:EDICstudy,Studydesign:Observationalstudybegunin1993(followingDCCTcloseout)in28medicalcentersintheUnitedStatesandCanada.DuringtheEDICstudy:glycemiclevelsnolongerdifferedsubstantiallyParticipants:1349(of1375)EDICvolunteerswhohadkidneyevaluationatyears7or8MainOutcomeMeasures：Developmentofmicroalbuminuria,clinical-gradealbuminuria,hypertension,orincreaseinserumcreatininelevel.,9,EDIC,Sustainedeffectofintensivetreatmentoftype1diabetesmellitusondevelopmentandprogressionofdiabeticnephropathy:TheEpidemiologyofDiabetesInterventionsandComplications(EDIC)Study.JAMA290:2159-2167,2003,10,EDIC,11,EDIC,Develophypertension:intensivetreatmentgroup29.9%conventional-treatment:40.3%;P001.Aserumcreatininelevelof2mg/dLorgreaterintensive-treatmentvstheconventional-treatmentgroup(5vs19,P=.004)Requireddialysisand/ortransplantationfewerpatientsexperiencedeitheroftheseoutcomesintheintensivegroup(4vs7,P=0.36).,12,EffectofGlycemicControlonKidneyFunctionandAlbuminuriainType2Diabetes,13,TheKumamotoStudy,Studydesign:arandomizedclinicaltrialParticipants110Japanesepatientswithtype2diabetesGroup:theprimarypreventioncohort:55withnoretinopathythesecondaryinterventioncohort:55withsimpleretinopathyIntervention:multipleinsulininjectiontherapy(MIT)groups(administeredthreeormoredailyinsulininjections)conventionalinsulininjectiontherapy(CIT)groups(administeredoneortwodailyintermediate-actinginsulininjections)Followup:8yearsMainOutcomeMeasures:Worseningofmicrovascularcomplications,14,43.5%,11.5%,ShichiriM,KishikawaH,OhkuboY,WakeN:Long-termresultsoftheKumamotoStudyonoptimaldiabetescontrolintype2diabeticpatients.DiabetesCare23:B21-B29,2000(suppl2),TheKumamotoStudy,40%,16%,Secondaryinterventioncohort,Primarypreventioncohort,15,TheKumamotoStudy,glycemicthresholdtopreventtheonsetandprogressionofdiabeticmicrovascularcomplicationswasasfollows:HbA1c6.5%,fastingbloodglucoseconcentration110mg/dl,2-hpostprandialbloodglucoseconcentration180mg/dl,16,UKPDS,Studydesign:randomizedclinicaltrialParticipants:3867newlydiagnosedpatientswithtype2diabetesIntervention:intensivemanagementusingasulfonylureaorinsulinconventionalmanagementwithdietaloneEndpoints:Threeaggregateendpointsanydiabetes-relatedendpoint(suddendeath,deathfromhyperglycaemiaorhypoglycaemia,fatalornon-fatalmyocardialinfarction,angina,heartfailure,stroke,renalfailure,amputation,vitreoushaemorrhage,retinopathyrequiringphotocoagulation,blindnessinoneeye,orcataractextraction);diabetes-relateddeath(deathfrommyocardialinfarction,stroke,peripheralvasculardisease,renaldisease,hyperglycaemiaorhypoglycaemia,andsuddendeath);all-causemortality,UKProspectiveDiabetesStudy(UKPDS)Group:Intensiveblood-glucosecontrolwithsulphonylureasorinsulincomparedwithconventionaltreatmentandriskofcomplicationsinpatientswithtype2diabetes(UKPDS33).Lancet352:837-853,1998,17,UKPDS,After9yearsofintensivetherapyRRreductionforthedevelopmentofmicroalbuminuriawas24%(P=0.0006)RRreductionforthedevelopmentofmacroalbuminuriawithinsulinorsulfonylureaswas33%at9years(4.4%versus6.5%,intensiveversusconventional),butthisfindingwasnotstatisticallysignificant67%riskreductionforadoublingofplasmacreatininelevelsat9years(0.71%oftheintensivegroupand1.76%oftheconventionalgroup;P=0.027).,18,UKPDS,theriskintheintensivegroupwas12%lower(p=0.029)foranydiabetes-relatedendpoint10%lower（p=0.34)foranydiabetes-relateddeath;6%lower(p=0.44)forall-causemortality.PatientsintheintensivegrouphadmorehypoglycaemicWeightgainwassignificantlyhigherintheintensivegroup(mean2.9kg)thanintheconventionalgroup(p8.6,HbA18.6,21,StudiesshownadequateglycaemiccontrolindiabeticpredialysisCRFpatientscanreducemorbidityandmortalityinthefirstyearsfollowingthestartofdialysis,YuCC,etal.PredialysisglycemiccontrolisanindependentpredictorofclinicaloutcomeintypeIIdiabeticsoncontinuousambulatoryperitonealdialysis.PeritDialInt1997;17:262268.WuMS,etalPre-dialysisglycemiccontrolisanindependentpredictorofmortalityintypeIIdiabeticpatientsoncontinuousambulatoryperitonealdialysis.PeritDialInt1999;19(Suppl.2):S179S183.SuzukiY,ArakawaM.,GejyoFandCollaborativeStudyGroup.Thetreatmentoftheuraemicdiabetic.Arewedoingenough?AviewfromJapan:FumitakeGejyoandCollaborateStudyGroup.NephrolDialTransplant1995;10(Suppl.7):4755.,22,GlycaemiccontrolinHDpatients,MoriokaT,EmotoM,TabataT,etal:Glycemiccontrolisapredictorofsurvivalfordiabeticpatientsonhemodialysis.DiabetesCare24:909-913,2001,23,TakeshiOomichi,etal；ImpactofGlycemicControlonSurvivalofDiabeticPatientsonChronicRegularHemodialysis:A7-yearobservationalstudyDiabetesCare29:1496-1500；2006,GlycaemiccontrolinHDpatients,24,GlycaemiccontrolinHDpatients,Kalantar-ZadehK,etal:A1Candsurvivalinmaintenancehemodialysispatients.DiabetesCare30:1049-1055,2007,25,GlycaemiccontrolinPDpatients,In2452diabeticPDnoassociationbetweenA1candsurvivalinunadjustedordiverselevelsofmultivariateadjustedmodel,PeritDialInt27(Supplement_3):21-2007,26,Managementofhyperglycemiaindiabetesandchronickidneydisease,27,.,血糖的控制,血糖的评估降糖目标及检测频率降糖治疗降糖药物胰岛素,28,血糖的评估,自我监测血糖（SMBG）指导病人进行SMBG，并且规律的针对对病人对技术掌握的能力以及病人对这些数据利用能力进行的评估对病人血糖控制情况的评估应该综合考虑病人自我监测血糖和最近HbA1c的结果糖化血红蛋白（HbA1c）HbA1c不仅反映病人过去2-3个月血糖的情况，而且也可以用来检测病人血糖仪的准确性以及自我监测血糖计划的充分性持续血糖监测(Continuousglucosemonitoring),29,降糖目标及检测频率,KDOQIClinicalPracticeGuidelinesandClinicalPracticeRecommendationsforDiabetesandChronicKidneyDisease:AmJKidneyDis49:S1-S180,2007(suppl2),30,NoninsulinHypoglycemicAgentsforManagementofHyperglycemiainCKD,InsulinSecretagoguesSulfonylureasNonsulfonylureaInsulinSecretagogues(glinides)Incretin-BasedInsulinSecretagoguesInsulinSensitizersBiguanidesThiazolidinedionesOtherMedications-GlucosidaseInhibitors,31,Sulfonylureas,bindingtotheSUreceptor1ofcellstimulateinsulinsecretionBloodGlucoseMostAffected：Fastingandpostprandial,32,Sulfonylureas,KDOQIClinicalPracticeGuidelinesandClinicalPracticeRecommendationsforDiabetesandChronicKidneyDisease:AmJKidneyDis49:S1-S180,2007(suppl2),33,NonsulfonylureaInsulinSecretagogues(glinides),BindtoSUreceptorinpancreaticcell(differentthanSUsite)stimulateinsulinreleaseaveryshorthalf-lifeanddurationofaction(3-4hours)-administeredshortlybeforemealsrelativelylowriskofhypoglycemiaBloodGlucoseMostAffected：Postprandial,34,glinides,瑞格列奈：Nodataforpatientswithcreatinineclearance20ml/min,35,Incretin-BasedInsulinSecretagogues,Theincretin(肠降血糖素)composedprimarilyof2peptides;glucose-dependentinsulinotropicpolypeptideglucagon-likepeptide1(GLP-1)Effectbyintestinallyderivedpeptideswhicharereleasedinthepresenceofglucoseornutrientsinthegutaugmentationofglucose-stimulatedinsulinsecretion,36,Incretin-BasedInsulinSecretagogues,IncretinsarerapidlyinactivatedbyenzymeDPP4(二肽基肽酶4)resultinginaveryshorthalf-life(minutes)Theincretinpathwayappearstobeattenuatedinpatientswithtype2diabetes,makingthepathwayatargetforthedevelopmentofnewpharmacological2approvedagentsExenatide(艾塞那肽)Sitagliptin(西他列汀),37,Incretin-BasedInsulinSecretagogues：Exenatide(艾塞那肽),aglucagon-likepeptide1(GLP-1)receptoranalogueresistanttoDPP4degradationmodestglycemicefficacytheonlyhypoglycemicagentassociatedwithweightlossadministeredsubcutaneously，twicedailyabout60minutesbeforemeals.mainsideeffectisdose-dependentnauseaandvomiting,38,Incretin-BasedInsulinSecretagogues：Sitagliptin(西他列汀）,aselectiveDPP4inhibitoramodesthypoglycemicefficacyAdvantagesofaverylowriskofhypoglycemialackofweightgainadministeredorallyoncedailywelltoleratedasmallincreasedriskofurinarytractinfectionsandnasopharyngitis,39,Incretin-BasedInsulinSecretagogues,Exenatide：doseadjustmentisnotrequiredforpatientswithacreatinineclearancegreaterthan30mL/min(0.5mL/s).InpatientswithCKDstage4/5,clearanceofexenatideissignificantlydecreased(10%ofnormal),anditsuseisneitherrecommendednorwelltolerated.,40,InsulinSensitizers,BiguanidesThiazolidinediones,41,InsulinSensitizers：Biguanides,decreasesglucoselevelsprimarilybydecreasinghepaticglucoseoutputpromotinginsulin-mediatedglucoseuptakeinperipheralinsulin-targettissuesoneofthemostefficaciousoralhypoglycemicagentsandisassociatedwithfavorableclinicaloutcomes.mostcommonadverseeffectisgastrointestinaldisturbanceaccumulatesasrenalfunctionworsens,especiallyatGFRslessthan60mL/minpatientswithCKDstage3orhighershouldnotbeadministeredmetformin.,42,InsulinSensitizers：Thiazolidinediones,Enhanceinsulinactionininsulin-targettissuesthroughbindingtoperoxisomeproliferatoractivatedreceptor(nucleartranscriptionfactorsinvolvedinglucoseandlipidhomeostasis)asloweronsetofaction(weekstomonths)WeightgainisthemostcommonadverseeffectcontraindicatedinpatientswithNYHAIIIorIVcardiacstatusandshouldbeusedwithcautioninpatientswithpreexistingedemanodoseadjustmentisrequiredinpatientswithCKD.Arecentmeta-analysiscombiningdatafrom42trialslinkedrosiglitazonetoanincreasedriskofcardiovasculardisease.,43,OtherMedications-GlucosidaseInhibitor,inhibitingtheintestinalbreakdownofoligosaccharides,therebydelayingdigestionofingestedcarbohydrates.lowerglycemicefficacyTheymaybeusedinpatientswithstage3CKD,shouldbeavoidedinthosewithstages4and5becausetheywerenotstudiedinpatientswithserumcreatininevaluesgreaterthan2mg/dL,44,表3慢性肾脏病病人降糖药物的选择和剂量调整,？,？,45,Insulintherapy,MetabolismofInsulinInsulincategoriesInsulintherapyinCKDpatients,46,MetabolismofInsulin,a51-aminoacidpeptidehormoneamolecularweightofapproximately6000DasynthesizedbypancreaticisletbetacellsHalf-life(t1/2)ofinsulinisshort(35min)notboundtoplasmaproteinsUnderfastingconditions,insulinsecretioniscontinuouswithasecretionrateofapproximately0.51unit/h.Insulinsecretionincreases310timeswithfoodingestionthetotaldailyinsulinsecretionatabout1832units,47,RenalMetabolismofInsulin,48,Insulincategories,rapid-actinginsulinanaloguesshort-actinginsulin(regularhuman)intermediate-actinginsulin(human)long-actinginsulinanalogues,49,AvailableTypesofInsulinbyComparativeAction,50,InsulinAnalogues,designedbymeansofrecombinantDNAtechnology,havestructuralmodificationsintheamino-acidsequenceofhumaninsulin,resultinginimproved(morephysiological)timeprofiles.Rapid-actinginsulinanalogues（lisproaspartglulisine）morerapidabsorptionandonsetofactionhighermaximumseruminsulinconcentrationsshorteractiondurationsthanforthesamedosesofregularhumaninsulinTwolong-actinginsulinanalogues（glargine；detemir）moredelayedabsorptionandreceptorbindingcapacity,51,Insulintherapyprinciples,(1)individualizingapproach(2)administratingadequateamountsofinsulin(3)providingphysiologicaltherapythroughadministrationofbothbasal(long-acting)andprandial(bolus)insulin(4)monitoringandadjustingfrequentlybasedonindividualresponsivenesstotherapy(5)monitorkidneyfunctioncloselyandadjustinsulindosesappropriatelyasGFRdecreases,NoahDetalManagementofGlycemiainPatientsWithDiabetesMellitusandCKD;AmericanJournalofKidneyDiseases,Vol50,No5(November),2007:pp865-879,52,InsulintherapyinCKDpatients,LittledataexistregardinginsulintherapyindiabeticpatientswithadvanceddegreesofrenalinsufficiencyIdealinsulintherapiesindiabeticpatientswithadvancedCRFaredifficulttoestablishthelackofpharmacokineticstudiesforthevarioustypesofinsulininpatientswithdifferentdegreesofrenalinsufficiencyabsenceoftherapeuticguidelinesthatdefineinsulinadjustmentsbasedonGFR,PedroIglesias1andJuanJ.Dez:Insulintherapyinrenaldisease:Diabetes,ObesityandMetabolism,2008,53,GlycemiccontrolinDiabetesPatientsonHD,mosthypoglycemicagentsisnotsignificantlyaffectedbyhemodialysis.long-actingsulfonylureasarenotappropriateShort-actingsulfonylureasmaybeusedatlowdosesThiazolidinedionescanalsobeusedwithoutdoseadjustment.insulinwillbethemostappropriatetherapy.Rapid-actinginsulinanaloguesareclearedquicklyandcanbeusedsafely.Long-actingbasalinsulincanbeusedinatlowdosesEatingpatterns,54,GlycemiccontrolinD