糖尿病血脂异常及其治疗

[主题词]12型糖尿病患者均有较高的冠心病发病率。胰岛素抵抗动脉粥样硬化研究发现糖尿目前糖尿病患者的血脂异常与动脉粥样硬化的关系已渐成定论。Lasko等对3132型糖尿病患者进行7年随访研究，发现低水平的高密度脂蛋白胆固醇（HDL-CHDL2-C、高水平的极低密度脂蛋白胆固醇（VLDL-C、VLDL-TG，甘油三脂（TG）]收缩压、空腹血糖浓度的升高均与冠状动脉疾病密切相关。Lamarche等研究发现：空腹胰B（apoB）LDLsLDL2型糖尿病患者发生缺血性心脏病的重要危险因素[5]Joslin155岁以前35%死于冠心病[6]。1TG升高。胰岛素能够抑制脂肪酶的活性，1型糖尿病患TG1LDL-C升高，HDL-C下降，伴2型糖尿病通常是遗传因素与环境因素相互作用的结果,往往在疾病的亚临床期就已存在血脂异常，T、L浓度升高，DCL的增加。2脂蛋白表型与家族混合型高脂血症极其相似，其血脂异常不能单纯通过血糖控制而得到纠正。rSannoio422VLDL、TG、胆LDL更具有致动脉粥样硬化作用[7]。对三个有不同糖耐量人群的LDL颗粒大小与胰岛素及前胰岛素之间的关系进行研究[8]LDL颗粒大小与前胰岛素呈负相关。前胰岛素是胰岛素的前体，仅少量由胰腺β细胞与胰岛素一同分泌。2型糖尿病患者前胰岛素分泌量明显增加[9]。前胰岛素有相对胰岛素有较差的降糖能力[10]。但是前胰岛素如何影响LDL颗粒大小仍处于探索中。目前认LDLTG有关[11]。2TG水平较高,这样VLDLLDLTGTG而胆固醇酯缺乏的LDL颗粒,LDLLDL-TGsLDL载脂蛋白及一些酶的氨基酸残基糖化，Apo-BLDLLDL流行病学研究发现[16]LDL-C水平密切相关，而且饱固醇、TG、HDL-C及各种载脂蛋白的水平，从而有益于减少糖尿病患者发生冠心病的危险2型糖尿病患者的胰岛素抵抗、血脂异常中占有重要地位，则对其进行10mg/dl12%，HDL-C10mg/dl亦使患冠心病的危险性增加22%，这说明对糖尿病患者进行积极的调脂治疗是大有益处的。目前，尽管尚无糖尿病患者。4S202例糖尿病患者，对该研究进行回顾性分析发现辛伐他汀能55%，较普通人群更为有效。CARE研究包括了14%有相同作用。StevenA等[21]对糖尿病血脂异常药物治疗的成本效益进行研究发现：糖尿病成人糖尿病患者理想的LDL-C、HDL-C、TG水平分别为〈2.6mmol/l、〉1.2mmol/lLDL-C〉3.4mmol/lLDL-C2.6mmol/lMNT和药物治疗。糖尿病患者存在多种血脂异常，处理各种血脂肥保持理想体重、改变不良生活方式如戒烟等对升高HDL-C的浓度有重要意义，尽管烟HDL-c的药物，但由于其与他汀类药物合用会增加肌溶解的危险性，而且TG的浓度，良好的血糖控制将明显降低TG，贝特类药物可通过过氧化体增生激活受体（PPAR）α来减药物对高水平的TG有较好疗效。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例具有轻度血脂FaganTC,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