糖尿病合并高血脂課件

血脂異常合併

糖尿病或代謝癥候群臺(tái)中榮民總醫(yī)院內(nèi)分泌暨新陳代謝科主治醫(yī)師李奕德血脂異常合併

糖尿病或代謝癥候群臺(tái)中榮民總醫(yī)院1糖尿病and高血脂高血脂是心臟血管疾病的主因糖尿病的角色?糖尿病and高血脂高血脂是心臟血管疾病的主因2USA2000:15M2025:21.9MJAPAN2000:6.9M2025:8.5MEUROPE2000:30.8M2025:38.5MAMERICAS(Ex-US)2000:20M2025:42MAFRICA2000:9.2M2025:21.5MASIA2000:71.8M2025:165.7MOCEANIA2000:0.8M2025:1.5MKingHetalDiabetesCare1998;21:1414-1431.Type2DiabetesPrevalenceIsProjectedtoReach300Millionby2025About155millionadultsworldwidediagnosedwithdiabetesin200083millionwomenand72millionmenType2DiabetesPrevalencewillreach300millionin2025USAJAPANEUROPEAMERICASAFRICA3PercentagePrevalenceofHyperglycemia

byAgeGroupinTaiwanAgeGroup<2030-3980+Definition:glucose>126ordrug.國(guó)民健康局.2003.20-2940-4950-5960-6970-79PercentagePrevalenceofHyperg4Incidencerate(%)IncreasedRiskofCVEvents

Over7yearsinType2DiabeticsMyocardialInfarctionStrokeCVDeathNondiabetic–MI(n=1,304)Diabetic+MI(169)Nondiabetic+MI(n=69)Diabetic–MI(n=890)P<0.001*P<0.001*P<0.001*-MI

+MI-MI

+MI-MI

+MI-MI

+MI-MI

+MI-MI

+MIHaffnerSMetalNEnglJMed1998;339:229-234.Incidencerate(%)IncreasedRi5PrevalenceofhyperglycemiawithCo-morbiddiseasesHTNHyperlipidemiaCHDCVAP<0.001PercentageDefinition:glucose>126ordrug.國(guó)民健康局.2003.Prevalenceofhyperglycemiawi6糖尿病的治療準(zhǔn)則A1cBloodpressureCholesterol(lipid)DietcontrolExerciseFactorsreductionTherapeuticLifetherapy糖尿病的治療準(zhǔn)則A1cTherapeuticLifeth7StamlerJetalDiabetesCare1993;16:434-444.心血管的死亡率/10,000人-年糖尿病

無(wú)糖尿病總膽固醇(mmol/L)020406080100120140<4.74.7–5.15.2–5.75.8–6.26.3–6.76.8–7.2>7.3160心血管死亡風(fēng)險(xiǎn)(MRFITstudy):

低膽固醇糖尿病患者比高膽固醇但無(wú)糖尿病的人高StamlerJetalDiabetesCare8糖尿病合併血脂異常之特性三酸甘油酯(Triglyceride)過(guò)高高密度脂蛋白膽固醇(HDL)較低低密度脂蛋白(LDL)顆粒較小、密度較密糖尿病合併血脂異常之特性三酸甘油酯(Triglyceride9糖尿病的apoB濃度更高DiabetesLDLparticles“Normal”LDL-Clevel,however:“Normal”LDL-ClevelNodiabetes

LDLparticlesNumberofLDLparticlesConcentrationofapoBLowerRiskHigherSmall,denseLDLwithmoreapoBAustinMA,EdwardsKLCurrOpinLipidol1996;7:167-171;AustinMAetalJAMA1988;260:1917-1921;SnidermanADetalDiabetesCare2002;25:579-582.apoBLDL-C糖尿病的apoB濃度更高DiabetesLDLpartic10根據(jù)UKPDS研究中﹕在第二型糖尿病中各種危險(xiǎn)因子的重要性

VariableLow-DensityLipoproteinCholesterolHigh-DensityLipoproteinCholesterolHemoglobinA1cSystolicBloodPressureSmokingPValue<0.00010.00010.00220.00650.056CoronaryArteryDisease(n=280)PositioninModelFirstSecondThirdFourthFifth*Adjustedforageandsex.TurnerRCetal.BMJ1998;316:823-828.根據(jù)UKPDS研究中﹕在第二型糖尿病中各種危險(xiǎn)因子的重要性11

CHD罹病風(fēng)險(xiǎn)增加%

LDL-C1mmol/L 57HDL-C0.1mmol/L –15收縮壓10mmHg 15HbA1c濃度1% 11抽菸也是增加CHD罹病風(fēng)險(xiǎn)的重要因子TurnerRCetalBMJ1998;316:823-828.這些數(shù)據(jù)證明，糖尿病患者有必要降低其LDL-C濃度，以降低CHD的罹病風(fēng)險(xiǎn)。在UKPDS研究中LDL-C是預(yù)測(cè)糖尿病患者CHD罹病風(fēng)險(xiǎn)時(shí)最有力的指標(biāo) CHD罹病風(fēng)險(xiǎn)增加%TurnerRCetal12ThePyramidofRecentTrials

RelativeSizeoftheVariousSegmentsofthePopulation4SCAREWOSCOPSAFCAPS/TexCAPSLIPIDVeryhighcholesterolwithCHDorMIModeratelyhighcholesterolinhighriskCHDorMINormalcholesterolwithCHDorMIHighcholesterolwithoutCHDorMINohistoryofCHDorMIThePyramidofRecentTrials

R13過(guò)去對(duì)心臟血管疾病的大型介入性（治療性）降血脂臨床試驗(yàn)的結(jié)果對(duì)糖尿病患一樣有效嗎？糖尿病合併高血脂癥的藥物治療效果過(guò)去對(duì)心臟血管疾病的大型介入性（治療性）降血脂臨床試驗(yàn)的結(jié)果14StudyDrugNo.BaselineLDL-C,mg/dl(mmol/L)LDL-CLoweringPrimaryPreventionAFCAPS/TexCAPSLovastatin155150(3.9)25%HPSSimvastatin3985127(3.3)30%SecondaryPreventionCAREPravastatin586136(3.6)28%4SSimvastatin202186(4.8)36%LIPIDPravastatin782150(3.9)25%Statins在大型心血管保護(hù)研究中﹕針對(duì)整個(gè)族群的分析(降LDL效果)DownsJRetal.JAMA1998;279:1615-1622HPSInvestigators.PresentedatAHA,2001GoldbergRBetal.Circulation1998;98:2513-2519PyoralaKetal.DiabetesCare1997;20:614-620HaffnerSMetal.ArchInternMed1999;159:2661-2667LIPIDStudyGroup.NEnglJMed1998;339:1349-1357.StudyDrugNo.BaselineLDL-C,mg15StudyDrugNo.CHDRisk

Reduction

(overall)CHDRiskReduction(diabetics)PrimaryPreventionAFCAPS/TexCAPSLovastatin15537%43%HPSSimvastatin398524%26%SecondaryPreventionCAREPravastatin58623%25%4SSimvastatin20232%55%LIPIDPravastatin78225%19%Statins在大型心血管保護(hù)研究中﹕針對(duì)糖尿病次族群的分析(降LDL效果)DownsJRetal.JAMA1998;279:1615-1622HPSInvestigators.PresentedatAHA,2001GoldbergRBetal.Circulation1998;98:2513-2519PyoralaKetal.DiabetesCare1997;20:614-620HaffnerSMetal.ArchInternMed1999;159:2661-2667LIPIDStudyGroup.NEnglJMed1998;339:1349-1357.StudyDrugNo.CHDRisk

Reductio16結(jié)果對(duì)心臟血管疾病而言，由過(guò)去的大型介入性（治療性）臨床試驗(yàn)事後分析(posthocanalysis)得知，糖尿病患只要接受積極降低血脂治療（尤其是statins藥物），便可得到與非糖尿病患一樣（甚至更多）的好處。結(jié)果對(duì)心臟血管疾病而言，由過(guò)去的大型介入性（治療性）臨床試驗(yàn)17糖尿病合并高血脂課件18CARDSStudyPatientpopulation:Enrolledat132sitesintheUKandIrelandType2diabeteswithnopreviousMIorCHD≥1otherCHDriskfactorplusLDL-C≤4.14mmol/L

(160mg/dL)andTG≤6.78mmol/L(600mg/dL)Aged40-75yearsColhounHM,etal.DiabetMed.2002;19:201-211.2,838patientsAtorvastatin10mg/dayPlaceboAtleast4years6-weekplacebolead-in

Pre-randomizationPlaceboCARDSStudyPatientpopulation:19RecruitmentandFollowUp1,398(99.1%)Completefollowup1,421(99.5%)Completefollowup1,410Allocatedplacebo4,053Screened3,249(80%)Enteredbaseline1,428Allocatedatorvastatin10mgdaily2,838(70%)Randomized

Meanfollow-upof3.7yearsinbothgroupsColhounHM,etal.DiabetMed.2002;19:201-211.RecruitmentandFollowUp1,39820TCandLDL-CLevelsPlaceboAtorvastatinTCandLDL-CLevelsPlaceboAtor21EffectofAtorvastatinonthePrimaryEndPoint:MajorCVEventsIncludingStrokeRelativeRiskReduction37%YearsPlacebo127eventsAtorvastatin83eventsCumulativehazard(%)051015012344.75P=0.001ColhounHM,BetteridgeDJ,DurringtonPN,etal.Lancet.2004;364:685-696.EffectofAtorvastatinonthe22CARDSSummarystatinprovidedbenefitsintype2diabeteswithnohistoryofCVDandwithnormaltomildly-elevatedcholesterollevels37%reductioninmajorCVDevents(P=0.001)48%reductioninstroke(P=0.016)27%reductioninall-causemortality(P=0.059)ColhounHM,etal.DiabetMed.2002;19:201-211.CARDSSummarystatinprovidedb23AdultTreatmentPanelIII(ATPIII)GuidelinesNationalCholesterolEducationProgramAdultTreatmentPanelIII(ATP24治療的主要目標(biāo)LDLcholesterolLDL的升高是心臟血管疾病的主因降低LDL可減少心臟血管疾病的風(fēng)險(xiǎn)ATPIII治療的主要目標(biāo)著重在LDL.治療的主要目標(biāo)LDLcholesterol25高危險(xiǎn)群CHDHistoryofCHDCHDriskequivalentsOtherclinicalformsofatheroscleroticdiseaseperipheralarterialdiseaseabdominalaorticaneurysmsymptomaticcarotidarterydiseaseDiabetes(糖尿病)Multipleriskfactorswitha10-yearriskforCHD>20%ATPIII高危險(xiǎn)群CHDATPIII26RiskCategoryCHDandCHDriskequivalentsMultiple(2+)riskfactors0-1oneriskfactorLDLGoal(mg/dL)

<100

<130 <160ThreeCategoriesofRiskthatModify

LDL-CholesterolGoalsATPIIIRiskCategoryLDLGoal(mg/dL)T27糖尿病合并高血脂課件28糖尿病合并高血脂課件29NCEPATPIIIdefinition:>3ofthefollowingcriteriaRiskfactorsDefininglevelAbdominalobesity:Waistcircumference>102cm,Men>88cm,WomenTriglycerides

>150mg/dLHDL-cholesterol<40mg/dL,Men

<50mg/dL,WomenBloodpressure

>130/85mmHgFastingglucose

>110mg/dLNCEPATPIIIdefinition:>3o30糖尿病合并高血脂課件31PrevalenceoftheMetabolicSyndrome

Age-SpecificPrevalenceoftheMetabolicSyndromeAmong8814USAdultsAgedatLeast20Years,NationalHealthandNutritionExaminationSurveyIII,1988-1994HarrisMI,etal.,DiabetesCare1998;21:518FordES,etal.,JAMA.2002Jan16;287(3):356-9.PrevalenceoftheMetabolicSy32PrevalenceoftheMetabolicSyndrome

FordES,etal.,JAMA.2002Jan16;287(3):356-9.PrevalenceoftheMetabolicSy33DifferenceinAsianWHOExpertconsultation.Lancet2004;363:157-163DifferenceinAsianWHOExpert34國(guó)內(nèi)成人肥胖定義身體質(zhì)量指數(shù)(BMI)(kg/m2)

腰圍(cm)

體重過(guò)輕BMI＜18.5正常範(fàn)圍18.5≦BMI＜24異常範(fàn)圍過(guò)重：24≦BMI＜27輕度肥胖：27≦BMI＜30中度肥胖：30≦BMI＜35重度肥胖：BMI≧35男性：≧90公分女性：≧80公分肥胖的判定國(guó)內(nèi)成人肥胖定義身體質(zhì)量指數(shù)(BMI)腰圍體重過(guò)輕BMI＜35MetabolicSyndrome,carotidatherosclerosisandLDLsizeMetabolicSyndrome,carotidat36LDLsizeinmetabolicsyndromeHultheJetal.,ArteriosclerThrombVascBiol2000;20:2140.LDLsizeinmetabolicsyndrome37糖尿病合并高血脂課件38GemfibrozilforinsulinresistanceRubinsHBetal.,ArchInternMed.2002;162:2597Gemfibrozilforinsulinresist39代謝癥候群(metabolicsyndrome)第二個(gè)治療目標(biāo)LDL控制之後的目標(biāo)標(biāo)準(zhǔn)腹部肥胖Men(腹圍)>102cm(90cm)Women(腹圍)>88cm(80cm)HightriglycemiaTG>150mg/dlLowHDLcholesterolMen<40mg/dlWomen<50mg/dl血壓高>130/>85mmHg空腹血糖高Plasmaglucose>110mg/dlATPIII代謝癥候群(metabolicsyndrome)第二個(gè)治40Triglycerides高可能原因肥胖(obesity)不運(yùn)動(dòng)(physicalinactivity)抽煙(cigarettesmoking)酗酒(excessalcoholintake)高碳水化合物飲食high-carbohydratediets(>60%ofenergyintake)疾病糖尿病Diabetes慢性腎衰竭Chronicrenalfailure腎病癥侯群nephroticsyndrome藥物corticosteroids,estrogens,retinoids,higherdosesofB-adrenergicblockingagents基因familialcombinedhyperlipidemia,familialhypertriglyceridemiafamilialdysbetalipoproteinemiaATPIIITriglycerides高可能原因ATPIII41Triglycerides嚴(yán)重度TriglycerideslevelNormal <150mg/dLBorderlinehigh 150–199mg/dLHigh 200–499mg/dLVeryhigh 500mg/dLNon-HDLCholesterolVLDL+LDL=Totalcholesterol–HDLTarget:LDL+30mg/dlATPIIITriglycerides嚴(yán)重度Triglycerides42治療triglycerides過(guò)高治療的主要目標(biāo)著重在LDL但當(dāng)TG>500mg/dl治療的目標(biāo)﹕先預(yù)防急性胰臟炎低脂肪飲食Verylowfatdiets(15%ofcaloricintake)使用降Triglyceride藥物(fibrateornicotinicacid)ATPIII治療triglycerides過(guò)高治療的主要目標(biāo)著重在LD43HDLCholesterol過(guò)低-原因-Triglycerides過(guò)高肥胖(obesity)不運(yùn)動(dòng)(physicalinactivity)糖尿病(type2diabetes)抽煙(cigarettesmoking)高碳水化合物飲食high-carbohydratediets(>60%ofenergyintake)

藥物beta-blockers,anabolicsteroids,progestationalagentsATPIIIHDLCholesterol過(guò)低-原因-Trig44HDLCholesterol過(guò)低-治療-治療的主要目標(biāo)著重在LDL增加運(yùn)動(dòng)及控制體重仍依上述原則TG>500ReducetriglyceridesbeforeLDLlowering

TG:200–499Non-HDLcholesterolissecondarytargetoftherapyTG<200considernicotinicacidorfibratesinpersonwithCHDorCHDriskATPIIIHDLCholesterol過(guò)低-治療-治療的主要目45TherapeuticLifertherapy

-DietcontrolandExcerciseTheOslodiet-heartstudy的11-year追蹤報(bào)告：至少三十年前就證實(shí)有效地預(yù)防心血管疾病 (LerenP,1970)

TherapeuticLifertherapy

-Di46FinnishDiabetesPreventionStudySubjects522patients,40-65y,CaucasiansIGTon2occasionsInterventions1.

Intensifieddietandexerciselifestyle5%reductioninbodyweightReductionindietaryfat<30%,saturatedfat<10%Increaseindietaryfiber,fruitsandvegetablesIncreaseactivity2. UsualcareNEnglJMed344:1343-1349,2001生活型態(tài)與糖尿病FinnishDiabetesPreventionSt47

FinnishDPS:DevelopmentofdiabetesintheinterventionandcontrolgroupsRiskreduction:58%Meanfollow-up:3.2yearsNEnglJMed344:1343-1349,2001生活型態(tài)與糖尿病FinnishDPS:Developmentofdi48USDiabetesPreventionProgramSubjects3234patients,>25y,45%minoritiesIGTwithfastingplasmaglucose>5.6mmol/LInterventions1. Intensifieddietandexerciselifestyle7%reductioninbodyweightincreasecalorieexpenditure700kcalperweek2. Metformin1700mgperday3. PlacebotabletDiabetesCare23:1619-1629USDiabetesPreventionProgram49USDPP:EffectondiabetesincidenceMetformin:31%decreaseinincidentdiabetesLifestyle:58%decreaseinincidentdiabetesReleasedearly(08/08/01)afterameanfollow-upof3yearsDiabetesCare23:1619-1629USDPP:Effectondiabetesinc50TherapeuticLifestyleChanges

NutrientCompositionofTLCDietNutrient

RecommendedIntakeSaturatedfat Lessthan7%oftotalcaloriesPolyunsaturatedfat Upto10%oftotalcaloriesMonounsaturatedfat Upto20%oftotalcaloriesTotalfat 25–35%oftotalcaloriesCarbohydrate 50–60%oftotalcaloriesFiber 20–30gramsperdayProtein Approximately15%oftotalcaloriesCholesterol Lessthan200mg/dayTotalcalories Balanceenergyintakeandexpenditure tomaintaindesirablebodyweight/

preventweightgainATPIIITherapeuticLifestyleChanges

51回顧三十年前，發(fā)表運(yùn)動(dòng)者比長(zhǎng)期辦公者對(duì)insulin反應(yīng)較好Bjorntorpetal.Metabolism1970;19:631-638.數(shù)天的不運(yùn)動(dòng)即造成insulin反應(yīng)差。Rudermanetal.Diabetes1979;28:89-92.單一次的運(yùn)動(dòng)即可改善insulin作用，而且甚至可達(dá)兩天之久。Mikinesetal.AmJPhysiol1988;254:E248-E259

若運(yùn)動(dòng)後給醣類飲食後，insulinsensitivity只維持了15小時(shí)Bogardusetal.JClinInvest1983;72:1605-1610.

但運(yùn)動(dòng)當(dāng)時(shí)的catacholamine升高也可能阻礙insulin作用。Kj?retal.JApplPhysiol1986;61:1693-1700.

回顧三十年前，發(fā)表運(yùn)動(dòng)者比長(zhǎng)期辦公者對(duì)insulin反應(yīng)較好52Insulin增加血糖的吸收及利用與insulinreceptor作用經(jīng)由一些protein下傳訊息Ex:insulinreceptorsubstrate(IRS)其中可經(jīng)由GLUT4(glucosetransporter)移至細(xì)胞膜上，以利glucose的傳送Insulin增加血糖的吸收及利用與insulinrece53運(yùn)動(dòng)增加insulinsensitivity的機(jī)轉(zhuǎn)運(yùn)動(dòng)增加insulinsensitivity的機(jī)轉(zhuǎn)54運(yùn)動(dòng)後，肌肉會(huì)比以前更強(qiáng)壯為了應(yīng)付下一次的運(yùn)動(dòng)增加protein合成增加glycogen貯存局部的效果明顯只運(yùn)動(dòng)一腳，發(fā)現(xiàn)有運(yùn)動(dòng)的一肢比另一肢insulinsensitivity較好。另一肢可能也會(huì)改善，只是沒有運(yùn)動(dòng)的那肢好。運(yùn)動(dòng)增加insulinsensitivityRichteretal.JApplPhysiol1984;246:E476運(yùn)動(dòng)後，肌肉會(huì)比以前更強(qiáng)壯為了應(yīng)付下一次的運(yùn)動(dòng)運(yùn)動(dòng)增加ins55運(yùn)動(dòng)增加insulinsensitivityWojtaszewskietal.ActaPhysiolScand2003;178:321運(yùn)動(dòng)增加insulinsensitivityWojtasz56Glycogen量與insulinsensitivityGlucose的吸收與消秏的glycogen成正比。Glycogen的合成與肌肉內(nèi)glycogen量成反相關(guān)。因GLUT4到表面的量與glycogen量成反向關(guān)係可能經(jīng)由AMPK(AMP-activatedproteinkinase)作用運(yùn)動(dòng)增加insulinsensitivityGlycogen量與insulinsensitivityG57運(yùn)動(dòng)增加insulinsensitivityWojtaszewskietal.ActaPhysiolScand2003;178:321運(yùn)動(dòng)增加insulinsensitivityWojtasz58運(yùn)動(dòng)與insulin作用機(jī)轉(zhuǎn)不同運(yùn)動(dòng)後改善insulinsensitivity是由於GLUT4出現(xiàn)於肌肉細(xì)胞膜上增多。藉由取得glucose增加使合成glycogen增多。由運(yùn)動(dòng)增加glucose的傳送與glycogen的合成與insulin經(jīng)由的機(jī)轉(zhuǎn)可能不同﹕運(yùn)動(dòng)產(chǎn)生GLUT4表現(xiàn)並不一定需要insulinreceptor,IR1/2,PI3K等物質(zhì)。與AMPK有關(guān)運(yùn)動(dòng)增加insulinsensitivity運(yùn)動(dòng)與insulin作用機(jī)轉(zhuǎn)不同運(yùn)動(dòng)後改善insulins59糖尿病合并高血脂課件60Conclusion

Theclinicalapproachtotreatmentofpatientswithdyslipidaemias-associatedMetabolicSyndromeAbroad-basedstrategyreversaloflipidabnormalities(elevatedLDL-C)reductionoftriglyceride-richlipoproteinsimprovementofinsulin-resistance.Lifestylemodifications(balanceddietandincreasedphysicalexercise)shouldfirstbeproposeddrugtherapytargetinghypertriglyceridaemiaandlowHDL-CcouldbeproposedinassociationwithdietandexerciseConclusion

Theclinicalapproa61

Thankyou foryourattention Thankyou62血脂異常合併

糖尿病或代謝癥候群臺(tái)中榮民總醫(yī)院內(nèi)分泌暨新陳代謝科主治醫(yī)師李奕德血脂異常合併

糖尿病或代謝癥候群臺(tái)中榮民總醫(yī)院63糖尿病and高血脂高血脂是心臟血管疾病的主因糖尿病的角色?糖尿病and高血脂高血脂是心臟血管疾病的主因64USA2000:15M2025:21.9MJAPAN2000:6.9M2025:8.5MEUROPE2000:30.8M2025:38.5MAMERICAS(Ex-US)2000:20M2025:42MAFRICA2000:9.2M2025:21.5MASIA2000:71.8M2025:165.7MOCEANIA2000:0.8M2025:1.5MKingHetalDiabetesCare1998;21:1414-1431.Type2DiabetesPrevalenceIsProjectedtoReach300Millionby2025About155millionadultsworldwidediagnosedwithdiabetesin200083millionwomenand72millionmenType2DiabetesPrevalencewillreach300millionin2025USAJAPANEUROPEAMERICASAFRICA65PercentagePrevalenceofHyperglycemia

byAgeGroupinTaiwanAgeGroup<2030-3980+Definition:glucose>126ordrug.國(guó)民健康局.2003.20-2940-4950-5960-6970-79PercentagePrevalenceofHyperg66Incidencerate(%)IncreasedRiskofCVEvents

Over7yearsinType2DiabeticsMyocardialInfarctionStrokeCVDeathNondiabetic–MI(n=1,304)Diabetic+MI(169)Nondiabetic+MI(n=69)Diabetic–MI(n=890)P<0.001*P<0.001*P<0.001*-MI

+MI-MI

+MI-MI

+MI-MI

+MI-MI

+MI-MI

+MIHaffnerSMetalNEnglJMed1998;339:229-234.Incidencerate(%)IncreasedRi67PrevalenceofhyperglycemiawithCo-morbiddiseasesHTNHyperlipidemiaCHDCVAP<0.001PercentageDefinition:glucose>126ordrug.國(guó)民健康局.2003.Prevalenceofhyperglycemiawi68糖尿病的治療準(zhǔn)則A1cBloodpressureCholesterol(lipid)DietcontrolExerciseFactorsreductionTherapeuticLifetherapy糖尿病的治療準(zhǔn)則A1cTherapeuticLifeth69StamlerJetalDiabetesCare1993;16:434-444.心血管的死亡率/10,000人-年糖尿病

無(wú)糖尿病總膽固醇(mmol/L)020406080100120140<4.74.7–5.15.2–5.75.8–6.26.3–6.76.8–7.2>7.3160心血管死亡風(fēng)險(xiǎn)(MRFITstudy):

低膽固醇糖尿病患者比高膽固醇但無(wú)糖尿病的人高StamlerJetalDiabetesCare70糖尿病合併血脂異常之特性三酸甘油酯(Triglyceride)過(guò)高高密度脂蛋白膽固醇(HDL)較低低密度脂蛋白(LDL)顆粒較小、密度較密糖尿病合併血脂異常之特性三酸甘油酯(Triglyceride71糖尿病的apoB濃度更高DiabetesLDLparticles“Normal”LDL-Clevel,however:“Normal”LDL-ClevelNodiabetes

LDLparticlesNumberofLDLparticlesConcentrationofapoBLowerRiskHigherSmall,denseLDLwithmoreapoBAustinMA,EdwardsKLCurrOpinLipidol1996;7:167-171;AustinMAetalJAMA1988;260:1917-1921;SnidermanADetalDiabetesCare2002;25:579-582.apoBLDL-C糖尿病的apoB濃度更高DiabetesLDLpartic72根據(jù)UKPDS研究中﹕在第二型糖尿病中各種危險(xiǎn)因子的重要性

VariableLow-DensityLipoproteinCholesterolHigh-DensityLipoproteinCholesterolHemoglobinA1cSystolicBloodPressureSmokingPValue<0.00010.00010.00220.00650.056CoronaryArteryDisease(n=280)PositioninModelFirstSecondThirdFourthFifth*Adjustedforageandsex.TurnerRCetal.BMJ1998;316:823-828.根據(jù)UKPDS研究中﹕在第二型糖尿病中各種危險(xiǎn)因子的重要性73

CHD罹病風(fēng)險(xiǎn)增加%

LDL-C1mmol/L 57HDL-C0.1mmol/L –15收縮壓10mmHg 15HbA1c濃度1% 11抽菸也是增加CHD罹病風(fēng)險(xiǎn)的重要因子TurnerRCetalBMJ1998;316:823-828.這些數(shù)據(jù)證明，糖尿病患者有必要降低其LDL-C濃度，以降低CHD的罹病風(fēng)險(xiǎn)。在UKPDS研究中LDL-C是預(yù)測(cè)糖尿病患者CHD罹病風(fēng)險(xiǎn)時(shí)最有力的指標(biāo) CHD罹病風(fēng)險(xiǎn)增加%TurnerRCetal74ThePyramidofRecentTrials

RelativeSizeoftheVariousSegmentsofthePopulation4SCAREWOSCOPSAFCAPS/TexCAPSLIPIDVeryhighcholesterolwithCHDorMIModeratelyhighcholesterolinhighriskCHDorMINormalcholesterolwithCHDorMIHighcholesterolwithoutCHDorMINohistoryofCHDorMIThePyramidofRecentTrials

R75過(guò)去對(duì)心臟血管疾病的大型介入性（治療性）降血脂臨床試驗(yàn)的結(jié)果對(duì)糖尿病患一樣有效嗎？糖尿病合併高血脂癥的藥物治療效果過(guò)去對(duì)心臟血管疾病的大型介入性（治療性）降血脂臨床試驗(yàn)的結(jié)果76StudyDrugNo.BaselineLDL-C,mg/dl(mmol/L)LDL-CLoweringPrimaryPreventionAFCAPS/TexCAPSLovastatin155150(3.9)25%HPSSimvastatin3985127(3.3)30%SecondaryPreventionCAREPravastatin586136(3.6)28%4SSimvastatin202186(4.8)36%LIPIDPravastatin782150(3.9)25%Statins在大型心血管保護(hù)研究中﹕針對(duì)整個(gè)族群的分析(降LDL效果)DownsJRetal.JAMA1998;279:1615-1622HPSInvestigators.PresentedatAHA,2001GoldbergRBetal.Circulation1998;98:2513-2519PyoralaKetal.DiabetesCare1997;20:614-620HaffnerSMetal.ArchInternMed1999;159:2661-2667LIPIDStudyGroup.NEnglJMed1998;339:1349-1357.StudyDrugNo.BaselineLDL-C,mg77StudyDrugNo.CHDRisk

Reduction

(overall)CHDRiskReduction(diabetics)PrimaryPreventionAFCAPS/TexCAPSLovastatin15537%43%HPSSimvastatin398524%26%SecondaryPreventionCAREPravastatin58623%25%4SSimvastatin20232%55%LIPIDPravastatin78225%19%Statins在大型心血管保護(hù)研究中﹕針對(duì)糖尿病次族群的分析(降LDL效果)DownsJRetal.JAMA1998;279:1615-1622HPSInvestigators.PresentedatAHA,2001GoldbergRBetal.Circulation1998;98:2513-2519PyoralaKetal.DiabetesCare1997;20:614-620HaffnerSMetal.ArchInternMed1999;159:2661-2667LIPIDStudyGroup.NEnglJMed1998;339:1349-1357.StudyDrugNo.CHDRisk

Reductio78結(jié)果對(duì)心臟血管疾病而言，由過(guò)去的大型介入性（治療性）臨床試驗(yàn)事後分析(posthocanalysis)得知，糖尿病患只要接受積極降低血脂治療（尤其是statins藥物），便可得到與非糖尿病患一樣（甚至更多）的好處。結(jié)果對(duì)心臟血管疾病而言，由過(guò)去的大型介入性（治療性）臨床試驗(yàn)79糖尿病合并高血脂課件80CARDSStudyPatientpopulation:Enrolledat132sitesintheUKandIrelandType2diabeteswithnopreviousMIorCHD≥1otherCHDriskfactorplusLDL-C≤4.14mmol/L

(160mg/dL)andTG≤6.78mmol/L(600mg/dL)Aged40-75yearsColhounHM,etal.DiabetMed.2002;19:201-211.2,838patientsAtorvastatin10mg/dayPlaceboAtleast4years6-weekplacebolead-in

Pre-randomizationPlaceboCARDSStudyPatientpopulation:81RecruitmentandFollowUp1,398(99.1%)Completefollowup1,421(99.5%)Completefollowup1,410Allocatedplacebo4,053Screened3,249(80%)Enteredbaseline1,428Allocatedatorvastatin10mgdaily2,838(70%)Randomized

Meanfollow-upof3.7yearsinbothgroupsColhounHM,etal.DiabetMed.2002;19:201-211.RecruitmentandFollowUp1,39882TCandLDL-CLevelsPlaceboAtorvastatinTCandLDL-CLevelsPlaceboAtor83EffectofAtorvastatinonthePrimaryEndPoint:MajorCVEventsIncludingStrokeRelativeRiskReduction37%YearsPlacebo127eventsAtorvastatin83eventsCumulativehazard(%)051015012344.75P=0.001ColhounHM,BetteridgeDJ,DurringtonPN,etal.Lancet.2004;364:685-696.EffectofAtorvastatinonthe84CARDSSummarystatinprovidedbenefitsintype2diabeteswithnohistoryofCVDandwithnormaltomildly-elevatedcholesterollevels37%reductioninmajorCVDevents(P=0.001)48%reductioninstroke(P=0.016)27%reductioninall-causemortality(P=0.059)ColhounHM,etal.DiabetMed.2002;19:201-211.CARDSSummarystatinprovidedb85AdultTreatmentPanelIII(ATPIII)GuidelinesNationalCholesterolEducationProgramAdultTreatmentPanelIII(ATP86治療的主要目標(biāo)LDLcholesterolLDL的升高是心臟血管疾病的主因降低LDL可減少心臟血管疾病的風(fēng)險(xiǎn)ATPIII治療的主要目標(biāo)著重在LDL.治療的主要目標(biāo)LDLcholesterol87高危險(xiǎn)群CHDHistoryofCHDCHDriskequivalentsOtherclinicalformsofatheroscleroticdiseaseperipheralarterialdiseaseabdominalaorticaneurysmsymptomaticcarotidarterydiseaseDiabetes(糖尿病)Multipleriskfactorswitha10-yearriskforCHD>20%ATPIII高危險(xiǎn)群CHDATPIII88RiskCategoryCHDandCHDriskequivalentsMultiple(2+)riskfactors0-1oneriskfactorLDLGoal(mg/dL)

<100

<130 <160ThreeCategoriesofRiskthatModify

LDL-CholesterolGoalsATPIIIRiskCategoryLDLGoal(mg/dL)T89糖尿病合并高血脂課件90糖尿病合并高血脂課件91NCEPATPIIIdefinition:>3ofthefollowingcriteriaRiskfactorsDefininglevelAbdominalobesity:Waistcircumference>102cm,Men>88cm,WomenTriglycerides

>150mg/dLHDL-cholesterol<40mg/dL,Men

<50mg/dL,WomenBloodpressure

>130/85mmHgFastingglucose

>110mg/dLNCEPATPIIIdefinition:>3o92糖尿病合并高血脂課件93PrevalenceoftheMetabolicSyndrome

Age-SpecificPrevalenceoftheMetabolicSyndromeAmong8814USAdultsAgedatLeast20Years,NationalHealthandNutritionExaminationSurveyIII,1988-1994HarrisMI,etal.,DiabetesCare1998;21:518FordES,etal.,JAMA.2002Jan16;287(3):356-9.PrevalenceoftheMetabolicSy94PrevalenceoftheMetabolicSyndrome

FordES,etal.,JAMA.2002Jan16;287(3):356-9.PrevalenceoftheMetabolicSy95DifferenceinAsianWHOExpertconsultation.Lancet2004;363:157-163DifferenceinAsianWHOExpert96國(guó)內(nèi)成人肥胖定義身體質(zhì)量指數(shù)(BMI)(kg/m2)

腰圍(cm)

體重過(guò)輕BMI＜18.5正常範(fàn)圍18.5≦BMI＜24異常範(fàn)圍過(guò)重：24≦BMI＜27輕度肥胖：27≦BMI＜30中度肥胖：30≦BMI＜35重度肥胖：BMI≧35男性：≧90公分女性：≧80公分肥胖的判定國(guó)內(nèi)成人肥胖定義身體質(zhì)量指數(shù)(BMI)腰圍體重過(guò)輕BMI＜97MetabolicSyndrome,carotidatherosclerosisandLDLsizeMetabolicSyndrome,carotidat98LDLsizeinmetabolicsyndromeHultheJetal.,ArteriosclerThrombVascBiol2000;20:2140.LDLsizeinmetabolicsyndrome99糖尿病合并高血脂課件100GemfibrozilforinsulinresistanceRubinsHBetal.,ArchInternMed.2002;162:2597Gemfibrozilforinsulinresist101代謝癥候群(metabolicsyndrome)第二個(gè)治療目標(biāo)LDL控制之後的目標(biāo)標(biāo)準(zhǔn)腹部肥胖Men(腹圍)>102cm(90cm)Women(腹圍)>88cm(80cm)HightriglycemiaTG>150mg/dlLowHDLcholesterolMen<40mg/dlWomen<50mg/dl血壓高>130/>85mmHg空腹血糖高Plasmaglucose>110mg/dlATPIII代謝癥候群(metabolicsyndrome)第二個(gè)治102Triglycerides高可能原因肥胖(obesity)不運(yùn)動(dòng)(physicalinactivity)抽煙(cigarettesmoking)酗酒(excessalcoholintake)高碳水化合物飲食high-carbohydratediets(>60%ofenergyintake)疾病糖尿病Diabetes慢性腎衰竭Chronicrenalfailure腎病癥侯群nephroticsyndrome藥物corticosteroids,estrogens,retinoids,higherdosesofB-adrenergicblockingagents基因familialcombinedhyperlipidemia,familialhypertriglyceridemiafamilialdysbetalipoproteinemiaATPIIITriglycerides高可能原因ATPIII103Triglycerides嚴(yán)重度TriglycerideslevelNormal <150mg/dLBorderlinehigh 150–199mg/dLHigh 200–499mg/dLVeryhigh 500mg/dLNon-HDLCholesterolVLDL+LDL=Totalcholesterol–HDLTarget:LDL+30mg/dlATPIIITriglycerides嚴(yán)重度Triglycerides104治療triglycerides過(guò)高治療的主要目標(biāo)著重在LDL但當(dāng)TG>500mg/dl治療的目標(biāo)﹕先預(yù)防急性胰臟炎低脂肪飲食Verylowfatdiets(15%ofcaloricintake)使用降Triglyceride藥物(fibrateornicotinicacid)ATPIII治療triglycerides過(guò)高治療的主要目標(biāo)著重在LD105HDLCholesterol過(guò)低-原因-Triglycerides過(guò)高肥胖(obesity)不運(yùn)動(dòng)(physicalinactivity)糖尿病(type2diabetes)抽煙(cigarettesmoking)高碳水化合物飲食high-carbohydratediets(>60%ofenergyintake)

藥物beta-blockers,anabolicsteroids,progestationalagentsATPIIIHDLCholesterol過(guò)低-原因-Trig106HDLCholesterol過(guò)低-治療-治療的主要目標(biāo)著重在LDL增加運(yùn)動(dòng)及控制體重仍依上述原則TG>500ReducetriglyceridesbeforeLDLlowering

TG:200–499Non-HDLcholesterolissecondarytargetoftherapyTG<200considernicotinicacidorfibratesinpersonwithCHDorCHDriskATPIIIHDLCholesterol過(guò)低-治療-治療的主要目107TherapeuticLifertherapy

-DietcontrolandExcerciseTheOslodiet-heartstudy的11-year追蹤報(bào)告：至少三十年前就證實(shí)有效地預(yù)防心血管疾病 (LerenP,1970)

TherapeuticLifertherapy

-Di108FinnishDiabetesPreventionStudySubjects522patients,40-65y,CaucasiansIGTon2occasionsInterventions1.

Intensifieddietandexerciselifestyle5%reductioninbodyweightReductionindietaryfat<30%,saturatedfat<10%Increaseindietaryfiber,fruitsandvegetablesIncreaseactivity2. UsualcareNEnglJMed344:1343-1349,2001生活型態(tài)與糖尿病FinnishDiabetesPreventionSt109

FinnishDPS:DevelopmentofdiabetesintheinterventionandcontrolgroupsRiskreduction:58%Meanfollow-up:3.2yearsNEnglJMed344:1343-1349,2001生活型態(tài)與糖尿病FinnishDPS:Developmentofdi110USDiabetesPreventionProgramSubjects3234patients,>25y,45%minoritiesIGTwithfastingplasmaglucose>5.6mmol/LInterventions1. Intensifieddietandexerciselifestyle7%reductioninbodyweightincreasecalorieexpenditure700kcalperweek2. Metformin1700mgperday3. PlacebotabletDiabetesCare23:1619-1629USDiabetesPreventionProgram111USDPP:EffectondiabetesincidenceMetformin:31%decreaseinincidentdiabetes