糖尿病血脂異常及其治療

[主題詞]12型糖尿病患者均有較高的冠心病發(fā)病率。胰島素抵抗動(dòng)脈粥樣硬化研究發(fā)現(xiàn)糖尿目前糖尿病患者的血脂異常與動(dòng)脈粥樣硬化的關(guān)系已漸成定論。Lasko等對(duì)3132型糖尿病患者進(jìn)行7年隨訪研究，發(fā)現(xiàn)低水平的高密度脂蛋白膽固醇（HDL-CHDL2-C、高水平的極低密度脂蛋白膽固醇（VLDL-C、VLDL-TG，甘油三脂（TG）]收縮壓、空腹血糖濃度的升高均與冠狀動(dòng)脈疾病密切相關(guān)。Lamarche等研究發(fā)現(xiàn)：空腹胰B（apoB）LDLsLDL2型糖尿病患者發(fā)生缺血性心臟病的重要危險(xiǎn)因素[5]Joslin155歲以前35%死于冠心病[6]。1TG升高。胰島素能夠抑制脂肪酶的活性，1型糖尿病患TG1LDL-C升高，HDL-C下降，伴2型糖尿病通常是遺傳因素與環(huán)境因素相互作用的結(jié)果,往往在疾病的亞臨床期就已存在血脂異常，T、L濃度升高，DCL的增加。2脂蛋白表型與家族混合型高脂血癥極其相似，其血脂異常不能單純通過血糖控制而得到糾正。rSannoio422VLDL、TG、膽LDL更具有致動(dòng)脈粥樣硬化作用[7]。對(duì)三個(gè)有不同糖耐量人群的LDL顆粒大小與胰島素及前胰島素之間的關(guān)系進(jìn)行研究[8]LDL顆粒大小與前胰島素呈負(fù)相關(guān)。前胰島素是胰島素的前體，僅少量由胰腺β細(xì)胞與胰島素一同分泌。2型糖尿病患者前胰島素分泌量明顯增加[9]。前胰島素有相對(duì)胰島素有較差的降糖能力[10]。但是前胰島素如何影響LDL顆粒大小仍處于探索中。目前認(rèn)LDLTG有關(guān)[11]。2TG水平較高,這樣VLDLLDLTGTG而膽固醇酯缺乏的LDL顆粒,LDLLDL-TGsLDL載脂蛋白及一些酶的氨基酸殘基糖化，Apo-BLDLLDL流行病學(xué)研究發(fā)現(xiàn)[16]LDL-C水平密切相關(guān)，而且飽固醇、TG、HDL-C及各種載脂蛋白的水平，從而有益于減少糖尿病患者發(fā)生冠心病的危險(xiǎn)2型糖尿病患者的胰島素抵抗、血脂異常中占有重要地位，則對(duì)其進(jìn)行10mg/dl12%，HDL-C10mg/dl亦使患冠心病的危險(xiǎn)性增加22%，這說明對(duì)糖尿病患者進(jìn)行積極的調(diào)脂治療是大有益處的。目前，盡管尚無糖尿病患者。4S202例糖尿病患者，對(duì)該研究進(jìn)行回顧性分析發(fā)現(xiàn)辛伐他汀能55%，較普通人群更為有效。CARE研究包括了14%有相同作用。StevenA等[21]對(duì)糖尿病血脂異常藥物治療的成本效益進(jìn)行研究發(fā)現(xiàn)：糖尿病成人糖尿病患者理想的LDL-C、HDL-C、TG水平分別為〈2.6mmol/l、〉1.2mmol/lLDL-C〉3.4mmol/lLDL-C2.6mmol/lMNT和藥物治療。糖尿病患者存在多種血脂異常，處理各種血脂肥保持理想體重、改變不良生活方式如戒煙等對(duì)升高HDL-C的濃度有重要意義，盡管煙HDL-c的藥物，但由于其與他汀類藥物合用會(huì)增加肌溶解的危險(xiǎn)性，而且TG的濃度，良好的血糖控制將明顯降低TG，貝特類藥物可通過過氧化體增生激活受體（PPAR）α來減藥物對(duì)高水平的TG有較好療效。冠心病，TC120-250mg/dl、TC/HDL-C〉4、TG90-450mg/dl，冠心病的死亡率WHODAIS研究[22]260例具有輕度血脂F(xiàn)aganTC,SowersJ:Type2diabetesmellitus:greatercardiovascularrisksandgreaterbenefitsoftherapy(Editorial).ArcInternMed159:1033-1034,1999.WagenknechtLE,D'AagostinoRBJr，HaffnerSM，SavagePJ，RewersM.Impairedtolerance,type2diabetesandcarotidwallthickness:theInsulinResistanceAtherosclerosisStudy.DiabetesCare1998:21:1812-1818.LaksoM.LehtoS.PenttilaI.PyoralaK.Lipidsandlipoproteinspredictingcoronaryheartdiseasemortalityandmorbidityinpatientswithnon-insulin-dependentdiabetes.CirculationRCTurner,HMillns,etc:Riskfactorsfforcoronaryarterydiseaseinnon-insulindependentdiabetesmellitus;UnitedKingdomprospectivediabetesstudy(UKPDS:23).BMJvolume31614March1998LamarcheB,TchernofA,MauriegeP,CantinB,DagenaisGR,LupienPJ,DespresJP.FastinginsulinandapolipoproteinBlevelsandlow-densitylipoproteinparticlesizeasriskfactorsforischemicheartdisease.JAMA1998:279;1955-1961KroleskiAS,KosinskkiEJ,WarramJH,etal.MagnitudeanddeterminantsofcoronaryarterydiseaseinJuvenile-onset,insulin-dependentdiabetesmellitus.AmJCardiol1987:59:750-5LamarcheB,TchernofA,MoorjaniS,CantinB,DagenaisGR,LupienPJ,Despres'JP:Small,denselow-densitylipoproteinparticlesasapredictoroftheriskofischemicheartdiseaseinmen:prospectiveresultsfromtheQuebecCardiovascularStudy.Circulation95:69-75,1997AndreasFesta:LDLParticleSizeinRelationtoInsulin,Proinsulin,andInsulinSensitivity.DiabetesCare22:1688-1693,1999TempleRC,CarringtonCA,LuzioSD,OwensDR,SchneiderAE,SobeyWJ,HalesCN:Insulindeficiencyinnon-insulin-dependentdiabetes.Lanceti:293-295,1989GallowayJA,HooperSA,SpradlinCT,HoweyDC,FrankBH,BowsherRRAndersonJH:biosynthetichumanproinsullin:reviewofchemistry,invitroandinvivorceptorbinding,animalandhumanpharmacologystudies,andclinicaltrialexperience.DiabetesCareLagrostL,GambertP,LallemantC;CobinedeffectsoflipidtransfersandlipolysisongradientgelpattensofhumanplasmaLDL.ArteeriosclerThromb1994:14:1327-1336.GIUGLIANOD,CerielloA,PaolissoG:Oxidativestressanddiabeticvascularcpmplications.DiabetesCare1996:19:257-267.CerielloA:Acutehyperglycaemiaandoxidativestressgeneration.DiaMed1997(supplPaolissoG,GuiglianoD:Oxidativestressandinsulinaction:Istherearelationship?Diabetologia1996:39:357-363.CerielloA,PirisiM:Isoxidativestressthethemissinglinkbetweeninsulinresistanceandatherosclerosis?Diabetologia1995:38:1484-1485.ElizabethJ,Mayer-Davis,SarahLevin,JulieA:HeterogeneityinAssociationsBetweenMacronutrientIntakeandLipoproteinProfileinIndividualsWithType2Diabetes.DiabetesCareAmericanDiabetesAssociation:Nutritionrecommendationandprinciplesforpeoplewithdiabetesmellitus(PosistionStatement).DiabetesCare1998:21:S32-S35.AmericanDiabetesAssociation:Diabetesandexercise(PositionStatement)DiabetesCareGrundySM,BaladyGJ,CriquiMH,FletcherG,GreenlandP,etal.Whentostartcholesterol-loweringtherapyinpatientswithcoronaryheartdisease;astatementforhealthcareprofessionalsfromtheAmericanHeartAssociationtaskforceonriskreduction.CirculationBarbaraV,Howard,DavidC,Robbins,MauriceL,Sievers,ElisaT.Lee,etal.LDLcholesterolasstrongpredictorofcoronaryheartdiseaseindiabeticIndividualswithInsulinResistanceandLowLDL:TheStrongHeartStudy.ArteriosclerThrambVacBiol.2000;20:830-835.StevenA.Grover,LouisCoupal,HannaZowall,MarcDoris,Cost-effectivenessofTreatinghyperlipidemiainthePresenceofDiabetes.Circulation.2000;102:722-727.StainerG.DiabetesAtherosclerosisInterventionStudy[DAIS]:astudyconductedincooperationwith