2型糖尿病患者严格血糖控制和心血管事件的预防.ppt

2型糖尿病患者严格血糖控制和心血管事件的预防 中山大学附属第一医院内分泌科肖海鹏 Challenge Tohavepatientsbelieveinyourguidanceforthemanagementoftheirdiabetesmellitus NationalGeographics 2004 August Prevalenceofobesityincreased61 between1991and2000Morethan60 ofUSadultsareoverweightOnly43 ofobesepersonsadvisedtoloseweightduringcheckupsBMIandweightgainmajorriskfactorsfordiabetes Prevalence DiabetesMeanbodyweight kg Year Mokdadetal DiabetesCare 2000 23 1278 Mokdadetal JAMA 1999 282 1519 Mokdadetal JAMA 2001 286 1195 PrevalenceofDiabetesandObesity Globalprevalenceofdiabetes 246millionpeoplewithdiabetesworldwide roughly6 oftheadultpopulationIn2007 thefivecountrieswiththelargestnumbersofpeoplewithdiabetesare India China UnitedStates Russia GermanyBy2025 thelargestincreasesindiabetesprevalencewilloccurinlow andmiddle incomecountriesEachyearanadditional7millionpeopleworldwidedevelopdiabetes DiabetesAtlas 3rdedition InternationalDiabetesFederation 2006 中国的2型糖尿病管理面临严峻的挑战 中国的糖尿病患者可能居世界之最 经济的迅速发展 带来了传统生活方式的根本性变革 导致了中国2型糖尿病患者的剧增 潘长玉301医院 Diabetescomplications Eachyear3 8milliondeathsworldwideareattributabletodiabetesDiabetesisassociatedwithcomplicationssuchas DiabeticneuropathyRenalfailureBlindnessMacrovasculardiseaseMacrovascularcomplicationsareamajorcauseofdeathinpeoplewithdiabetes 心血管疾病在糖尿病者中的比率 新诊断的2型糖尿病患者 25 总糖尿病人群 50 占糖尿病死亡原因 65 75 AmHeartJ1999 138 5330 欧洲心脏调查结果 n 2107 n 2854 TheEuroHeartSurveyondiabetesandtheheart EuropeanHeartJournal 2004 25 1880 1890 43 509例高危人群中9 125例合并心血管疾病OGTT结果 任一心血管事件 n 9 125 NGTI IFGIGTDM 相对比例 PresentationofNovartisSatellitesymposiumduringESC2004 Munich Germany NAVIGATOR GAMI 急性心梗患者中的糖代谢异常 心肌梗死患者 BartnikM etal JInternMed 2004Oct 256 4 288 97 中国心脏调查结果 汇总 n 3513 中华内分泌代谢杂志2006 22 7 Riskofcardiovasculardisease CVD inrelationtoHbA1c TheARICStudy RelativeriskofCVD n 1626 p 0 001 5 2 5 2 5 7 5 7 6 5 6 5 8 2 8 2 HbA1c Ajustedforage gender race smoking BMI visceralobesity physicalactivity BPanddyslipidemia Adaptedfrom Selvin E etcoll Arch Int Med 165 1910 1916 2005 GAMI 新诊断高血糖是心肌梗死后 无心血管事件存活 的预测因素 BartnikM etal EurHeartJ 2004 25 22 1990 7 中位数随访时间 34月 Diabetespatientsrequiringglucose loweringtherapyandnon diabeticswithapriormyocardialinfarctioncarrythesamecardiovascularrisk Apopulationstudyof3 3millionpeopleCirculation117 1945 54 2008 All3 3mioDanesolderthan30yearswerefollowedfrom1997to2002bynationwideregistersMedicationtreateddiabetespatientsandnondiabeticswithandwithoutapriormyocardialinfarctionwerecomparedAtbaseline71 801Daneshadmedicationtreateddiabetesand79 575hadapriormyocardialinfarctionRelativeriskforCVDmortalitywas2 42inmenwithdiabetesmellituswithoutapriormyocardialinfarctionand2 44innondiabeticmenwithapriormyocardialinfarction P 0 60 HazardRatio Diabetes Glucose andCVDisease DMisanestablishedriskfactorforCVDInDM higherglucoselevels A1cpredicthigherCVrisk StrattonIM etal BMJ2000 321 405 412 12 riseper1 riseinA1C P 035 Fatal NonfatalStroke HazardRatio 14 riseper1 riseinA1C P 0001 10 1 0 5 Fatal NonfatalMI 10 43 riseper1 riseinA1C P 0001 10 1 0 5 Amputation DeathfromPVD 6 5 7 8 9 16 riseper1 riseinA1C P 021 HeartFailure 6 5 7 8 9 10 UKProspectiveDiabetesStudy Bloodglucoseandvascularriskindiabetes UKPDS 高血糖和心血管风险 越来越多的2型糖尿病患者出现心血管并发症UKPDS表明高血糖和心血管疾病之间存在流行病学上的关联但是严格的血糖控制能否降低该风险 ACCORD ADVANCE VADT等大型研究就是针对上述问题而设计 ACCORD 2型糖尿病强化降糖的效应研究 多中心研究 77研究中心 美国 加拿大10 251例患者 平均年龄62 2岁 强化治疗组 目标A1c 6 0 v标准治疗组1 3有心血管病史或2个以上心血管危险因素一级终点 非致死性心梗或卒中 心血管死亡 ACCORD 结果 ResultsofACCORD 糖尿病心血管风险控制行动 ACCORD 关于执行过程的分析HbA1c降低过快 4个月下降1 4 频发严重低血糖 16 2 TZD 92 胰岛素 77 用量过多平均体重增加3 5Kg 4人中有1人增加 10Kg 过于严格的血糖控制目标 HbA1c 6 0 VADT 退伍军人2型糖尿病血糖控制和血管并发症的研究 美国多中心研究1791退伍军人 平均年龄60 4yrs 97 为男性强化治疗组 A1c下降1 5 v标准治疗组40 有既往心血管病史一级终点 主要心血管事件的发生时间 复合终点 VADT 结果和分析 平均随访5 6年A1c6 9 A1c在6个月内降低2 心血管终点和死亡率上没有显著性差异体重增加9Kg严重低血糖发生率21 2 ADVANCE协作组研究2型糖尿病强化降压 降糖和血管事件结果 2型糖尿病患者严格血糖控制和血管结局 ADVANCE 析因设计 ADVANCE 血糖结果 ADVANCE 终点结果 微血管和大血管复合终点结果 主要大血管事件 全因死亡 微血管事件 ADA2008AnualMeetinginSanFranciscoNopositivetrialeffectofIntensiveglucoseloweringonmacrovascularcomplicationsintype2diabetes atleastinthetypesofpatientsstudied ACCORDADVANCEVADT 比较 ACCORD ADVANCE VADT研究 HazardRatiosforthePrimaryOutcomeandDeathfromAnyCauseinPrespecifiedSubgroups HazardRatiosforthePrimaryOutcomeandDeathfromAnyCauseinPrespecifiedSubgroups NEnglJMed 2003 348 2294 303 DCCT EDIC 早期代谢控制的益处 颈动脉内膜厚度 DCCT EDICStudy累积的心血管事件数 欧洲糖尿病协会减少2型糖尿病心血管风险英国前瞻性糖尿病研究20年干预研究结束后10年随访结果 1997 2007 Mean 95 CI UKPDS结束10年后随访结果 HbA1c的变化 磺脲类 胰岛素vs 常规治疗 微血管疾病风险比 心梗风险比 全因死亡风险比 早期血糖控制所带来的延续效应 LegacyEffect 研究结束后随访8 5年结果 1RuryR Holmanetal NEnglJMed 2008 359 15 1618 20 RRR RelativeRiskReduction P LogRank 强化治疗 磺脲类 胰岛素 vs 常规治疗 2型糖尿病强化组长期随访结果UKPDS 延迟效应 实际意义 提示 血糖记忆 效应需要尽早及严格血糖控制可能获得长期的心血管获益 47 Steno 2PostTrialaim 1Toexaminewhetheranintensifiedmultifactorialinterventionsimilartocurrentguidelineshasanimpactonmortalityinpatientswithtype2diabetesandmicroalbuminuria 2Toexaminewhetherriskreductionsalreadyachievedforbothmacro andmicrovasculardiseasewithintensifiedmultifactorialinterventionweresustainedinaclinicalsettingoutsidethestructuredframeworkofaclinicaltrial STENO 2PercentageofPatientsWhoReachedtheIntensive TreatmentGoalsataMeanof7 8Years G dePetal NEJM 2003 348 383 393 STENO 2CompositeEndPointofDeathfromCVCauses NonfatalMI CABG PCI NonfatalStroke Amputation orSurgeryforPeripheralAtheroscleroticArteryDisease G dePetal NEJM 2003 348 383 393 Steno 2研究 2型糖尿病多因素干预对死亡率的影响 NumbersatriskConventionalIntensive Steno 2PostTrial Mortality 8080 8078 7775 6972 6365 5162 4357 HR 0 54 0 32 0 89 P 0 015 3039 Yearsoffollow up Percentageofpatientsdying GaedePetal NEJM358 580 591 2008 Implicationsofthesefindingsforclinicalcare TreatmenttoA1Ctargetsbeloworaround7 intheyearssoonafterthediagnosisofdiabetesisassociatedwithlong termreductioninriskofmacrovasculardiasease Untilmoreevidencebecomesavailable thegeneralgoalof 7 appearsreasonable ADA B level Implicationsofthesefindingsforclinicalcare Forselectedindividuals includingthosewithshortdurationofDM longlifeexpectancy andnosignificantcardiovasculardisease HbA1Clessthan7 isreasonableifthiscanbeachievedwithoutsignificanthypoglycemiaorotheradverseeffectsoftreatment Implicationsofthesefindingsforclinicalcare Conversely lessstringentA1Cgoals 7 maybeappropriateforpatientswithahistoryofseverehypoglycemia limitedlifeexpectancy advancedmicrovascularormacrovascularcomplications orextensivecomorbidconditionsorthosewithlong standingdiabetesinwhomthegeneralgoalisdifficulttoattain Implicationsofthesefindingsforclinicalcare ForprimaryandsecondaryCVDriskreductioninpatientswithdiabetes providersshouldcontinuetofollowtheevidence basedrecommendationsforbloodpressuretreatment lipid loweringwithstatins aspirinprophylaxis smokingcessation andhealthylifestylebehaviors 糖尿病 Gettingthebalanceright生活质量和长寿 谢谢