糖尿病合并高血脂

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?USA2000:15M2025:21.9MJAPAN2000:6.9M2025:8.5MEUROPE2000:30.8M2025:38.5MAMERICAS(Ex-US)2000:20M2025:42MAFRICA2000:9.2M2025:21.5MASIA2000:71.8M2025:165.7MOCEANIA2000:0.8M2025:1.5MKingHetalDiabetesCare1998;21:1414-1431.Type2DiabetesPrevalenceIsProjectedtoReach300Millionby2025About155millionadultsworldwidediagnosedwithdiabetesin200083millionwomenand72millionmenType2DiabetesPrevalencewillreach300millionin2025PercentagePrevalenceofHyperglycemia

byAgeGroupinTaiwanAgeGroup<2030-3980+Definition:glucose>126ordrug.國民健康局.2003.20-2940-4950-5960-6970-79Incidencerate(%)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.PrevalenceofhyperglycemiawithCo-morbiddiseasesHTNHyperlipidemiaCHDCVAP<0.001PercentageDefinition:glucose>126ordrug.國民健康局.2003.糖尿病的治療準(zhǔn)則A1cBloodpressureCholesterol(lipid)DietcontrolExerciseFactorsreductionTherapeuticLifetherapyStamlerJetalDiabetesCare1993;16:434-444.心血管的死亡率/10,000人-年糖尿病

無糖尿病總膽固醇(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糖尿病的人高糖尿病合併血脂異常之特性三酸甘油酯(Triglyceride)過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.

CHD罹病風(fēng)險(xiǎn)增加%

LDL-C

1mmol/L 57HDL-C

0.1mmol/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)測糖尿病患者CHD罹病風(fēng)險(xiǎn)時(shí)最有力的指標(biāo)ThePyramidofRecentTrials

RelativeSizeoftheVariousSegmentsofthePopulation4SCAREWOSCOPSAFCAPS/TexCAPSLIPIDVeryhighcholesterolwithCHDorMIModeratelyhighcholesterolinhighriskCHDorMINormalcholesterolwithCHDorMIHighcholesterolwithoutCHDorMINohistoryofCHDorMI過去對(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StudyDrugNo.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.CHDRisk

Reduction

(overall)CHDRiskReduction(diabetics)PrimaryPreventionAFCAPS/TexCAPSLovastatin15537%43%HPSSimvastatin398524%26%SecondaryPreventionCARE

Pravastatin58623%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.結(jié)果對(duì)心臟血管疾病而言，由過去的大型介入性（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。CARDSStudyPatientpopulation: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-randomizationPlaceboRecruitmentandFollowUp1,398(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.TCandLDL-CLevelsPlaceboAtorvastatinEffectofAtorvastatinonthePrimaryEndPoint:MajorCVEventsIncludingStrokeRelativeRiskReduction37%YearsPlacebo127eventsAtorvastatin83eventsCumulativehazard(%)051015012344.75P=0.001ColhounHM,BetteridgeDJ,DurringtonPN,etal.Lancet.2004;364:685-696.CARDSSummarystatinprovidedbenefitsintype2diabeteswithnohistoryofCVDandwithnormaltomildly-elevatedcholesterollevels37%reductioninmajorCVDevents(P=0.001)48%reductioninstroke(P=0.016)27%reductioninall-causemortality(P=0.059)ColhounHM,etal.DiabetMed.2002;19:201-211.AdultTreatmentPanelIII(ATPIII)GuidelinesNationalCholesterolEducationProgram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.高危險(xiǎn)群CHDHistoryofCHDCHDriskequivalentsOtherclinicalformsofatheroscleroticdiseaseperipheralarterialdiseaseabdominalaorticaneurysmsymptomaticcarotidarterydiseaseDiabetes(糖尿病)Multipleriskfactorswitha10-yearriskforCHD>20%ATPIIIRiskCategoryCHDandCHDriskequivalentsMultiple(2+)riskfactors0-1oneriskfactorLDLGoal(mg/dL)

<100

<130 <160ThreeCategoriesofRiskthatModify

LDL-CholesterolGoalsATPIIINCEPATPIIIdefinition:>3ofthefollowingcriteriaRiskfactorsDefininglevelAbdominalobesity:Waistcircumference>102cm,Men>88cm,WomenTriglycerides

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

<50mg/dL,WomenBloodpressure

>130/85mmHgFastingglucose

>110mg/dLPrevalenceoftheMetabolicSyndrome

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

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

腰圍(cm)

體重過輕BMI＜18.5正常範(fàn)圍18.5≦BMI＜24異常範(fàn)圍過重：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MetabolicSyndrome,carotidatherosclerosisandLDLsizeLDLsizeinmetabolicsyndromeHultheJetal.,Arterioscler

Thromb

Vasc

Biol2000;20:2140.GemfibrozilforinsulinresistanceRubinsHBetal.,ArchInternMed.2002;162:2597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/dlATPIIITriglycerides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,familialhypertriglyceridemiafamilialdysbetalipoproteinemia

ATPIIITriglycerides嚴(yán)重度TriglycerideslevelNormal <150mg/dLBorderlinehigh 150–199mg/dLHigh 200–499mg/dLVeryhigh 500mg/dLNon-HDLCholesterolVLDL+LDL=Totalcholesterol–HDLTarget:LDL+30mg/dlATPIII治療triglycerides過高治療的主要目標(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)ATPIIIHDLCholesterol過低-原因-Triglycerides過高肥胖(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<200considernicotinicacidorfibratesinpersonwithCHDorCHDriskATPIIITherapeuticLifertherapy

-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)

FinnishDiabetesPreventionStudySubjects522patients,40-65y,CaucasiansIGTon2occasionsInterventions1.

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

FinnishDPS:DevelopmentofdiabetesintheinterventionandcontrolgroupsRiskreduction:58%Meanfollow-up:3.2yearsNEnglJMed344:1343-1349,2001生活型態(tài)與糖尿病USDiabetesPreventionProgramSubjects3234patients,>25y,45%minoritiesIGTwithfastingplasmaglucose>5.6mmol/LInterventions1. Intensifieddietandexerciselifestyle7%reductioninbodyweightincreasecalorieexpenditure700kcalperweek2. Metformin1700mgperday3. PlacebotabletDiabetesCare23:1619-1629USDPP:EffectondiabetesincidenceMetformin:31%decreaseinincidentdiabetesLifestyle:58%decreaseinincidentdiabetesReleasedearly(08/08/01)afterameanfollow-upof3yearsDiabetesCare23:1619-1629TherapeuticLifestyleChanges

NutrientCompositionofTLCDietNutrient

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

preventweightgainATPIII回顧三十年前，發(fā)表運(yùn)動(dòng)者比長期辦公者對(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.JAppl

Physiol1986;61:1693-1700.

Insulin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的傳送運(yùn)動(dòng)增加insulinsensitivity的機(jī)轉(zhuǎn)運(yùn)動(dòng)後，肌肉會(huì)比以前