资源描述：
《胰岛素及口服降糖药ppt培训课件》由会员上传分享，免费在线阅读，更多相关内容在教育资源-天天文库。
糖尿病发病机理与治疗药物进展南京中医药大学国家规范化中药药理实验室朱荃 AphorismWehavetwoendswithacommonlink; Withonewesit,withonewethink. Successdependsonwhichweuse; Headswewin,tailswelose!--Authorunknown 荷兰50岁以上糖尿病的病死率 前言 我國的發病情況中國80年代<1%,目前升到3.6-5%，其中60歲以上達6%，發病人數也由80年代的6百萬目前增加到3千萬。老年糖尿病患者中90%以上為2型糖尿病.截今為止，該病尚無根治的辦法.近年來許多國家崇尚自然療法，中醫藥日益受到青睞. 胰岛素的发现C.H.Best.Banting'sandBest'sexperimentswerecrudelyconductedanddidnotsubstantiateBanting'sidea,whichwasphysiologicallyincorrect.Buttheirapparentlyfavourableresultsencouragedgreaterefforts,whichculminatedinthewinterof1921-22inthediscoveryofinsulinbyateamofresearchersthatincludedMacleod,Banting,J.B.CollipandBest. 人类第一次用胰腺提取物治疗糖尿病----多伦多大学年轻学者Banting,SirFrederickGrant 等,在狗实验成功的基础上完成的nightof31Oct1920 胰岛素的发现者们 结构 胰岛素的空间构型 胰岛β细胞分泌胰岛素 IsletsofLangerhans,specializedcellslocatedinhumanpancreasthatsecreteinsulin,glucagon,andgastrin.Pancreas 胰岛素的药理作用糖代谢增加葡萄糖的转运氧化和酵解促进糖原的合成与贮存，抑制糖原分解和异生 胰岛素受体与葡萄糖 葡萄糖的氧化与酵解 胰岛素的药理作用脂肪代谢增加脂肪酸的转运，促进脂肪合成抑制其分解，减少游离脂肪酸和酮体的生成 胰岛素的药理作用蛋白质代谢增加氨基酸的转运和蛋白质的合成抑制蛋白质的分解 胰岛素的药理作用 胰岛素的药理作用 胰岛素的药理作用 胰岛素的药理作用 一、二型糖尿病对葡萄糖的利用 Resistin,Obesity,andInsulinResistance—TheEmergingRoleoftheAdipocyteasanEndocrineOrgan Whyhastheincidenceoftype2diabetesincreasedsorapidly?Considerableepidemiologicevidencepointstoexcesscaloricintakeandphysicalinactivityasthemajorreasons.Achronicimbalancebetweenenergyexpenditureandenergyintakecausesobesity,whichisoneofthemostpotentriskfactorsforinsulinresistanceandtype2diabetes. Adipocyte--thepathwaysresponsibleforenergybalanceRecentstudieshavetransformedourthinkingabouttheadipocyte.Itisnolongerregardedasapassivedepotforstoringexcessenergyintheformoftriglyceride,butasacellthatactivelyregulatesthepathwaysresponsibleforenergybalanceandwhoseactivityiscontrolledbyacomplexnetworkofhormonalandneuronalsignals(Figure1).Indeed,theadipocytesecreteschemicalmessengersthatincludeleptin,tumornecrosisfactor,angiotensinogen,andadiponectin.2 leptinissecretedbytriglyceride-ladenadipocytes,travelsthroughthecirculation,crossestheblood–brainbarrier,andreachesthehypothalamus,whereitmodulatesahostofneuroendocrineandautonomicnervoussystemactivities,resultingindecreasedfoodintakeandincreasedenergyexpenditure.Resistin,aswellastumornecrosisfactor,adiponectin,freefattyacids,andpossiblyotherfactorsreleasedbyadipocytes,actinperipheraltissuestoinfluencesensitivitytoinsulinandothercellularandmetabolicprocessesinvolvedintheuseandpartitioningofsubstrates. ResistinNewadipocytehormone——Mouseresistincontains114aminoacidsandcirculatesasahomodimeroftwopeptidesjoinedbyadisulfidebridge.4Resistinmaybeanimportantlinkbetweenincreasedfatmassandinsulinresistance.secretedbyadipocytesandactsatdistantsites.Theobesemicethatserumlevelsofresistinaremarkedlyincreasedandaredecreasedbyrosiglitazoneandotherthiazolidinedionesthatincreasesensitivitytoinsulinpointtoresistinasamediatorofinsulinresistance. ManyquestionsremainSinceenergymetabolismdiffersinmiceandhumans,isthephysiologyofresistininmicerelevanttothatinhumans?Willresistinantagonistsbeeffectiveforthetreatmentoftype2diabetes,andifso,willtheybebetterorworsethanthiazolidinediones?Amorecompleteunderstandingofhowadipocytesregulateenergybalanceawaitsthediscoveryofotherproteinsproducedbythesecellsandtheelucidationofthecomplexsignalingnetworkofwhichmoleculeslikeresistinareapart. 体内过程口服无效易被消化酶破坏注射给药皮下注射吸收快代谢快t½为9-10分钟，作用可维持数小时在肝肾内灭活中长效制剂为混悬剂 Diabetes,InsulinSecretion,andthePancreaticBeta-CellMitochondrionZhangetal.recentlyprovidedcompellingevidencethatamitochondrialanioncarriercalleduncouplingprotein2isacriticalmodulatorofinsulinsecretionandthatanincreaseinthisproteinmaycausebeta-celldysfunction.1 Thestepsthatlinkchangesinglucoselevelstoinsulinsecretionarewellcharacterized(Figure1A).Followingitsentryintothebetacell,glucoseisphosphorylatedbyglucokinase.Thisrate-limitingenzymaticstepconstitutesaglucosesensor,sinceitallowsrapidandpreciseadjustmentstobemadeinresponsetochangesinextracellularglucoselevels.Furtherproductsofglucosemetabolismenterthemitochondrialrespiratorychain,whichusesthemtogenerateadenosinetriphosphate(ATP).TheincreaseinATPinhibitsATP-sensitivepotassiumchannels,whichinturnstimulatesinsulinsecretion.Thehypoglycemiceffectofsulfonylureas,whicharewidelyusedinthetreatmentoftype2diabetes,isduetotheinhibitionofthesechannels.IntheprocessofgeneratingATP,controlofthecouplingbetweenoxygenconsumptionandATPsynthesisisessential,sinceitmodulatesATPlevels. Thepancreaticbetacellisuniquelyequippedtoadaptinsulinsecretiontoambientglucoselevels(PanelA).uptakeofglucosebybetacells.Glucokinase,thefirstenzymeoftheglycolyticpathway,servesasaglucosesensor.ATPandADPareexchangedbetweenthecytosolandthemitochondrionbytheadeninenucleotidecarrier(ANC).AnincreaseintheratioofATPtoADPinhibitsATP-sensitivepotassium(KATP)channelsandprovokesadecreaseinthedepolarizationoftheplasmamembrane,whichopensvoltage-gatedCa2+channels.Theincreaseintheintracellularcalciumconcentrationandenergy-dependentcellulareventssuchastheactivationofATPasescontributestotheexocytosisofinsulin-containinggranules. Anincreaseinuncouplingprotein2levelsmayresultfromtheincreaseinfreefattyacidlevelsassociatedwithobesityandtheinsulin-resistancesyndrome(PanelB).Theincreaseinuncouplingprotein2decreasesmitochondrialcouplingofATPsynthesiswithoxygenconsumption,whichmaydecreasetheproductionofreactiveoxygenspecies(abenefit)orimpairinsulinsecretion(adetriment). 临床应用胰岛素依赖型糖尿病非胰岛素依赖型糖尿病饮食控制或用口服降糖药物无效者糖尿病各种急性或严重并发症酮症高血糖高渗性昏迷合并重度感染、消耗性疾病、高热、妊娠、创伤的个性糖尿病 不良反应过敏反应牛胰岛素作为异体蛋白引起过敏反应以猪胰岛素代替低血糖正规胰岛素应用过量出现饥饿感出汗心跳加快焦虑震颤严重的引起昏迷惊厥，脑损伤死亡长效胰岛素作用缓慢胰岛素耐受性加大剂量免疫抑制剂（胰岛素抗体）---其他动物胰岛素高纯度胰岛素 口服降糖药磺酰脲双胍类А-葡萄糖苷酶抑制剂 磺酰脲类甲苯磺丁脲氯苯丙脲格列吡嗪等 药理作用触发胰岛素的释放提高靶细胞对胰岛素的敏感性 临床应用胰岛功能尚存的非胰岛素依赖型糖尿病氯磺丙脲促进抗利尿素的分泌治尿崩症 不良反应胃肠不适恶心呕吐腹痛腹泻大剂量氯磺丙脲引起中枢症状神经错乱嗜睡眩晕共济失调粒细胞胆汁郁积黄疸肝损害持久性低血糖 药物相互作用较高的血浆蛋白结合率能与其他药物竞争血浆蛋白结合点与其他药物同用时（水杨酸吲哚美辛青霉素等）可提高有利药物的浓度引起低血糖。 双胍类甲福明（metformin二甲双胍）苯乙福明（phenformin苯乙双胍）降低食物中葡萄糖的吸收及糖原异生，促进组织摄取葡萄糖轻症糖尿病尤其是肥胖者，饮食控制无效食欲下降恶心腹部不适腹泻乳酸血症 А-葡萄糖苷酶抑制药新型口服降糖药在小肠上皮刷状缘与碳水化合物竞争水解碳水化合物的酶，减慢葡萄糖产生速度延缓吸收限制单糖食物阿卡波糖碳水化合物a-葡萄糖苷酶葡萄糖 胰岛素增敏剂增加肌肉脂肪组织对胰岛素的敏感性塞唑二烷酮Thiazolidinediones的衍生物罗格列酮Rosiglitazone环格列酮ciglitatone吡格列酮piglitatone恩格列酮englitatone 中药制剂中藥醛糖還原酶抑制劑及蛋白非酶糖化抑制劑防治糖尿病慢性併發症的研究也取得了可喜的成績，益糖通脈膠囊(芪蛭降糖通脈膠囊)就是這方面的代表。益糖通脈膠囊(芪蛭降糖通脈膠囊)的主要成份為含葡萄糖醛酸的黃芪和含凝血酶的水蛭，它能改善血液流變性,降低全血比黏度,提高胰島功能降低血糖,改善早期腎病生化指標和臨床症狀。 苦瓜 BitterMelon(Momordicacharantia)Bittermelon,alsoknownasbalsampear,isatropicalvegetablewidelycultivatedinAsia,AfricaandSouthAmerica,andhasbeenusedextensivelyinfolkmedicineasaremedyfordiabetes.Thebloodsugarloweringactionofthefreshjuiceorextractoftheunripefruithasbeenclearlyestablishedinbothexperimentalandclinicalstudies. Bittermeloniscomposedofseveralcompoundswithconfirmedanti-diabeticpropertiesCharantin,extractedbyalcohol,isahypoglycaemicagentcomposedofmixedsteroidsthatismorepotentthanthedrugtolbutamidewhichisoftenusedinthetreatmentofdiabetes.Momordicaalsocontainsaninsulin-likepolypeptide,polypeptide-P,whichlowersbloodsugarlevelswheninjectedsubcutaneouslyintotype1diabeticpatients. Theoraladministrationof50-60mlofthejuicehasshowngoodresultsinclinicaltrialsExcessivelyhighdosescancauseabdominalpainanddiarrhea.Smallchildrenoranyonewithhypoglycemiashouldnottakebittermelon,sincethisherbcouldtheoreticallytriggerorworsenlowbloodsugar,orhypoglycemia.Furthermore,diabeticstakinghypoglycemicdrugs(suchaschlorpropamide,glyburide,orphenformin)orinsulinshouldusebittermelonwithcaution,asitmaypotentiatetheeffectivenessofthedrugs,leadingtoseverehypoglycemia. Currenttreatmentapproachestotype2diabetesmellitus:successesandshortcomingsAmJManagCare2002Oct;8(16Suppl):S460-71CollinsFM.QueenCityPhysicians,Cincinnati,Ohio,USA. 策略Intype2diabetes,insulinresistanceandarelativebeta-celldefectaretheunderlyingpathologicproblemsleadingtohyperglycemia.Notably,insulinresistanceisalsoassociatedwithobesity,dyslipidemia,andhypertension.Diabetescanbedefinedasadiseaseofacceleratedcardiovasculardeteriorationassociatedwithelevatedbloodglucoselevels. 方案Glycemiccontrolpatientsneedmedicationtolowerglucosetonear-normallevels.Therapeuticoptionsfortreatinghyperglycemiaincludesulfonylureas（黄酰脲类）andotherinsulinsecretagogues,biguanides（双呱类）,alpha-glucosidaseinhibitors（葡萄糖苷酶抑制剂）,thiazolidinediones（塞唑二烷酮）,andinsulin.Anantidiabeticagentthatimprovesinsulinsensitivityisanexcellentchoiceforearlytreatmentoftype2diabetesbecauseitmaydelayorpreventcomplicationsassociatedwiththisdisease.Becauseoftheprogressivenatureoftype2diabetes,aggressiveinterventionearlyinthecourseofthedisease,includingcombinationtherapy,isoftennecessary. Enterovirusinfectionsandtype1diabetes.JDRFCenterforPreventionofType1Diabetes,Tampere,Finland.blhehy@uta.fi Type1(insulin-dependent)diabetesisatypicalorgan-specificautoimmunediseasewhereinsulin-producingbetacellsaredestroyedbyimmunemediatedmechanisms.Theriskofthediseaseismodulatedbygeneticfactors,mainlygenescodingforhumanleukocyteantigens(HLA), possibleviraltriggersofthediseasehavebeensoughtforyearsbuttheiridentificationhasbeenverydifficult.Recently,theideathatthegroupofenterovirusesmaybeparticularlyimportantinthepathogenesis.Recentmolecularstudieshaveconsiderablystrengthenedthishypothesisbyshowingthatenterovirusgenomeispresentinthebloodofdiabeticpatients. enterovirusinfectionsmayinitiatethebeta-celldamagingprocessseveralyearsbeforeclinicaldiabetesisdiagnosed.Ecologicalstudieshavealsoindicatedsimilaritiesintheepidemiologyoftype1diabetesandpoliomyelitis（小儿麻痹症）-awell-knownenterovirusdisease.thiswouldofferattractivepossibilitiestopreventthediseaseorpartofit,forexample,byanenterovirusvaccin MousemodelsofinsulinresistanceAmJPhysiolEndocrinolMetab2002May;282(5):E977-81HribalML,OrienteF,AcciliD.NaomiBerrieDiabetesCenter,DepartmentofMedicine,CollegeofPhysicians&SurgeonsofColumbiaUniversity,NewYork,NewYork10032,USA. Thehallmarksoftype2diabetesareimpairedinsulinactioninperipheraltissuesanddecreasedpancreaticbeta-cellfunction.Classically,thetwodefectshavebeenviewedasseparateentities,withinsulinresistancearisingprimarilyfromimpairedinsulin-dependentglucoseuptakeinskeletalmuscle,andbeta-celldysfunctionarisingfromimpairedcouplingofglucosesensingtoinsulinsecretion. Targetedmutagenesisandtransgenesisinvolvingcomponentsoftheinsulinactionpathwayhavechangedourunderstandingofthesephenomena.Itappearsthattheroleofinsulinsignalinginthepathogenesisoftype2diabeteshasbeenoverestimatedinclassicinsulintargettissues,suchasskeletalmuscle,whereasithasbeenoverlookedinliver,pancreaticbeta-cells,andbrain,whichhadbeenthoughtnottobeprimaryinsulintargets.Wereviewrecentprogressandtrytoreconcileareasofapparentcontroversysurroundinginsulinsignalinginskeletalmuscleandpancreaticbeta-cells. 美国天然产物治疗糖尿病的概况Useofcomplementaryandalternativemedicineamongpersonswithdiabetesmellitus:resultsofanationalsurvey.YehGY,EisenbergDM,DavisRB,PhillipsRS.DivisionforResearchandEducationinComplementaryandIntegrativeMedicalTherapies,OsherInstitute,HarvardMedicalSchool,401ParkDrive,Suite22A,Boston,MA02215,USA.gyeh@caregroup.harvard.edu Complementaryandalternativemedicine(CAM)amongpersonswithdiabetesmellitusresidingintheUnitedStates.Datafroma1997-1998nationalsurvey(n=2055)onCAMusewereexamined.Ninety-fiverespondentsreportedhavingdiabetes,ofwhom57%reportedCAMuseinthepastyear;fewerrespondents(35%)reportedusespecificallyfordiabetes. TherapiesusedfordiabetesincludedSolitaryprayer/spiritualpractices(28%)Herbalremedies(7%)Commercialdiets(6%)Folkremedies(3%). EffectsofAmericanginsengberryextractonbloodglucoselevelsinob/obmiceXieJT,AungHH,WuJA,AttelAS,YuanCS.TangCenterforHerbalMedicineResearch,DepartmentofAnesthesiaandCriticalCare,PritzkerSchoolofMedicine,UniversityofChicago,Illinois60637,USA. Americanginsengberryextractindiabeticob/obmice.Animalsreceiveddailyintraperitoneal(IP)extract150mg/kgfor12days.Ondays5and12,significantlylowerfastingbloodglucoselevelscomparedtoday0(p<0.05).GlucosetoleranceimprovedsignificantlyTheAUCdecreasedby31.8%onday12comparedtoday0(p<0.01).Inaddition,asignificantreductioninbodyweight(p<0.01)andasignificantincreaseinbodytemperature(p<0.01) Evaluationofthehypoglycemicandanti-oxidantactivitiesofMorindaofficinalisinstreptozotocin-induceddiabeticratsSingaporeMedJ2002Feb;43(2):077-85SoonYY,TanBK.DepartmentofPharmacology,FacultyofMedicineNationalUniversityofSingapore,Singapore. AnethanolicextractofthedriedrootsofMorindaofficinalis(巴戟天)anditsthreefractions(ethylacetate,n-butanolandwater).Thehypoglycemiceffectsofthreedifferentcrudeextractanditsfractionsinnormalanddiabeticrats.Administrationoftheextractat150mg/kgtwicedailyfor10daysTheeffectsonthefastingserumglucose,insulin,totalcholesterol,triglycerides,bodyweight,foodintake,fluidintake,hepaticsuperoxidedismutase(SOD),catalase(CAT)activities,reducedglutathione(GSH), andrenalMDAlevelsweremonitored.RESULTS:Thecrudeethanolicextractreducedthefastingserumglucoselevelsofthediabeticratssignificantlyat150mg/kgbutincreasedthoseofthenormalratssignificantlyat600mg/kgonly.Thewaterfractiondemonstratedadosedependenthypoglycemiceffectinthediabeticratswhereasthen-butanolfractionincreasedthefastingserumglucoselevelsofthediabeticratssignificantlyat50mg/kgonly HepaticandrenalMDAleveldecreasedandsignificantlyincreasedthehepaticSODandCATactivitiesaswellasGSHlevels.CONCLUSION:TheresultsindicatethatthedriedrootsofMorindaofficinalispossesshypoglycemic,hyperglycemicandanti-oxidantproperties. Alternationofhepaticantioxidantenzymeactivitiesandlipidprofileinstreptozotocin-induceddiabeticratsbysupplementationofdandelionwaterextract.ClinChimActa2002Mar;317(1-2):109-17ChoSY,ParkJY,ParkEM,ChoiMS,LeeMK,JeonSM,JangMK,KimMJ,ParkYB.DepartmentofFoodandNutrition,YeungnamUniversity,Kyongsan712-749,SouthKorea Dandelionwaterextract(蒲公英水提取物，DWE),anherbalmedication,mayhaveaneffectontheactivityandmRNAexpressionofhepaticantioxidantenzymesandlipidprofile（增加肝脏抗氧酶的表达，改善血脂状况）Theextractwassupplementedin2.4gofaDWE/kgdiet.TheDWEsupplementsignificantlydecreasedtheserumglucoseconcentrationinthediabeticrats. ThehepaticsuperoxidedismutaseandcatalaseactivitiessignificantlyincreasedandtheGSH-Pxactivitydecreasedinthediabeticrats.WhentheDWEwasgiventothediabeticrats,theantioxidantenzymeactivityrevertedtonear-controlvalues.However,therewasnodifferenceinthemRNAexpressionconcentrationsoftheseenzymesbetweenthegroups.Themalondialdehyde(MDA)contentwassignificantlyhigherinthediabeticgroupthaninthenondiabeticgroup. However,theDWEsupplementloweredthehepaticMDAconcentrationinthediabetic-inducedrats.TheDWEsupplementalsoloweredthetotalcholesterolandtriglycerideconcentrationsintheserumandhepatictissue,whileincreasingtheserumHDL-cholesterolinthediabeticrats.CONCLUSIONS:ADWEsupplementcanimprovethelipidmetabolismandisbeneficialinpreventingdiabeticcomplicationsfromlipidperoxidationandfreeradicalsindiabeticrats.改善脂质代谢，预防并发症 Theeffectof3-monthingestionofGinkgobilobaextractonpancreaticbeta-cellfunctioninresponsetoglucoseloadinginindividualswithnon-insulin-dependentdiabetesmellitus.连续服用银杏叶提取物如何KudoloGB.DepartmentofClinicalLaboratorySciences,SchoolofAlliedHealthSciences-MSC6246,UTHSCSA,7703FloydCurlDrive,SanAntonio,TX78229-3900,USA. ItisconcludedthatingestionofGinkgobilobaextractbyanNIDDMsubjectmayincreasethehepaticmetabolicclearancerateofnotonlyinsulinbutalsothehypoglycemicagents.Theresultisreducedinsulin-mediatedglucosemetabolismandelevatedbloodglucose.银杏叶提取物加快肝脏对胰岛素即将糖药物的代谢，因而升高血糖 药师在家庭治疗糖尿病的作用Exploringtheclinicalpharmacist'sroleinimprovinghomecareforpatientswithdiabetesSetterSM,CorbettCF,CookD,JohnsonSB.WashingtonStateUniversity'sCollegeofPharmacy,USA. Astudyexaminingtheroleofaclinicalpharmacistwasperformedinahomecareagencyinwhich105clientswereinterviewedandtheirrespectivechartsreviewedwiththefollowingresults:37%wereincorrectlyclassifiedastotypeofdiabetes,serumcreatinineandHbA1cvalueswerenotcommonlyrecorded,andclientstendedtohavecomplexdrugregimenswithalargenumberofpotentialdrug-relatedproblems.Theclinicalpharmacist'spotentialimpactinthisenvironmentisgreatbasedonthedatagatheredfromthisstudy AntihyperglycemicEffectofOolongTeainType2Diabetes.DiabetesCare2003Jun;26(6):1714-1718HosodaK,WangMF,LiaoML,ChuangCK,IhaM,ClevidenceB,YamamotoS.ResearchCenter,Suntory,Osaka,Japan.DepartmentofFoodandNutrition,ProvidenceUniversity,Taichung,Taiwan.ChorngKuangHospital,Miaoli,Taiwan.SchoolofMedicine,UniversityofTokushima,Tokushima,Japan.BeltsvilleHumanNutritionResearchCenter,U.S.DepartmentofAgriculture,Beltsville,Maryland. OBJECTIVETodeterminetheefficacyofoolongteaforloweringplasmaglucoseintype2diabeticpatientsinMiaoli,Taiwan.RESEARCHDESIGNANDMETHODS-Atotalof20free-livingsubjectswhohadtype2diabetesandtookhyperglycemicdrugsasprescribedwereenrolledinthepresentstudy.Subjectsconsumedoolongtea(1,500ml)orwaterfor30dayseachinarandomizedcrossoverdesign.Teawasnotconsumedfor14dayspriortotreatments. RESULTS:oolongteamarkedlyloweredconcentrationsofplasmaglucosefrom229.0+/-53.9to162.2+/-29.7mg/dl,P<0.001)andfructosaminefrom409.9+/-96.1to323.3+/-56.4micromol/l,P<0.01),whereasthewatercontrolgrouphadnotchanged208.7+/-61.0vs.232.3+/-63.1mg/dlforglucoseandfrom368.4+/-85.0to340.0+/-76.1micromol/lforfructosamine).CONCLUSIONS:-Oolongteamaybeaneffectiveadjuncttooralhypoglycemicagentsinthetreatmentoftype2diabetes CombinationLipid-loweringTherapyinDiabetes.CurrDiabRep2003Jun;3(3):263-8DavidsonMH.ChicagoCenterforClinicalResearch,Rush-Presbyterian-St.Luke'sMedicalCenter,1725WestHarrisonStreet,Suite1159,Chicago,IL60612,USA.mdavidson@protocare.com ObjectiveOwingtotheNationalCholesterolEducationProgramAdultTreatmentPanelIIIrecommendationsthatpatientswithdiabetesrequirealow-densitylipoprotein(LDL)lessthan100mg/dLandanon-high-densitylipoprotein(HDL)lessthan130mg/dL,frequently,combinationlipid-loweringtherapyisrequired.However,diabeticpatientsarecommonlyonmultiplemedicationsandhaverenalimpairment.Therefore,theriskofmyopathywithstatintherapyismarkedlyincreased. Thesafetyoflipid-loweringtherapycanbesignificantlyimprovedbyavoidinghigh-dosestatinsincombinationwithfibrates,especiallygemfibrozil.Toachievenon-HDLgoalscombiningfenofibrate,orifglucoseiswellcontrolled,niacin,withastatin(nottoexceed40mg),maysignificantlyreducetheriskofmyopathy.FordiabeticpatientswhorequireadditionalLDLlowering,ezetimibemayprovideasafecombinationtoastatintoachievetheLDLgoaloflessthan100mg/dL.
