心内科医生应掌握的糖尿病知识.ppt

心内科医生应该了解的糖尿病知识,北京大学人民医院纪立农,30,20,10,0,7,8,9,10,11,12,1,2,3,4,5,6,7,8,9,A.M.,P.M.,早餐,午餐,晚餐,75,50,25,0,基础胰岛素,基础血糖,胰岛素(U/mL),血糖(mg/dL),时间,健康人胰岛素和血糖曲线,-细胞的胰岛素分泌调节,Transportandphosphorylation,Glucose-6-P,Glucose,Glycolysis,ATP(ATP/ADP),Mitochondrialmetabolism,Granuleformationandtrafficking,Depolarization,Ca2+,Insulin,KATPchannel,GLUT2,Sulfonylureas,Sulfonylureareceptor,Genetranscription,葡萄糖在体内的代谢,胰岛素抵抗,肝糖生成,内源性胰岛素,餐后血糖,空腹血糖,内源性胰岛素,IGT,47年,“诊断糖尿病”,ClinicalDiabetesVolume18,Number2,2000,显性糖尿病,糖尿病的自然病程,微血管,大血管,2型糖尿病的自然病程与血糖变化相关的其它异常,糖尿病前期,糖尿病发生并发症出现,并发症发展,残废,死亡,胰岛素抵抗,失明,肾衰,心血管病,截肢,正常血糖,糖尿病,病理基础：,其它异常：,血脂紊乱高血压凝血功能异常炎症,血糖紊乱与心血管病变高血糖的分类高血糖与心血管病变血糖调节紊乱与心血管病变糖尿病心血管病变应激性高血糖与心血管病变血糖外的因素与心血管病变,内容,ReavenGMetal.Diabetologia.1977;13:201-206.,P.8r,不同糖耐量状态个体在OGTT试验中的血糖曲线,IGT,空腹血糖150mg/dL,正常上限,空腹血糖110-150mg/dL,正常,Time(hr),血糖(mg/dL),0,1/2,1,2,3,400,360,320,280,240,200,160,120,80,1997PPS,血糖紊乱与心血管病变高血糖的分类高血糖与心血管病变血糖调节紊乱与心血管病变糖尿病心血管病变应激性高血糖与心血管病变血糖外的因素与心血管病变,内容,FPGmmol/l,2hrPPGmmol/l,IGR,DM,NomenclatureanddescriptiontermdefinedbyFPGand2hrPPG,NomenclatureanddescriptiontermdefinedbyFPGand2hrPPG,IFG,IFG+IGT,IGT,FPGmmol/l,2hrPPGmmol/l,DM,NomenclatureanddescriptiontermdefinedbyFPGand2hrPPG,IFH,CH,IFG,IFG+IGT,IPH,IGT,FPGmmol/l,2hrPPGmmol/l,7.0,6.1,7.811.1,ShawJE,etal.Diabetologia42:1050,1999ResnickHE,etal.DiabetesCare23:176,2000Barrett-ConnerE,etal.DiabetesCare21:1236,1998,5.6,空腹和餐后血糖增高的临床表现,血糖紊乱与心血管病变高血糖的分类高血糖与心血管病变血糖调节紊乱与心血管病变糖尿病心血管病变应激性高血糖与心血管病变血糖外的因素与心血管病变,内容,Impairedglucosetoleranceisacardiovascularriskfactor(FunagataStudy),TominagaMetal.DiabetesCare1999,Cumulativecardiovascularsurvival,0,1.00,0.99,0.98,0.97,0.96,0.95,0.94,1,2,3,4,5,6,7,Year,Survivalratescardiovasculardisease,NormalIGT(2hPG7.811.0mmol/L)Diabetes(2hPG11.1mmol/L),ParisProspectiveStudy10-yearfollow-up,EschwegeEetal.HormMetabRes1985,Impairedglucosetoleranceprogressivelyincreasesriskofcoronaryheartdiseasemortality,心血管死亡率与餐后高血糖具有线性正相关关系,TuomilehtoJ.UnpublisheddatafromDECODE,CumulativehazardcurvesforWHO2hglucosecriteriaadjustedbyage,sex,andstudycentre,TheDECODEstudygroupTHELANCETVol354August21,1999619,IGT,normal,diabetes,研究设计,安慰剂t.i.d.(n=715),阿卡波糖100mgt.i.d.(n=714),1,0,36,6,12,18,24,30,时间（月）,1,2,3,4,5,6,7,8,9,10,11,12,13,14,就医（次）,安慰剂n=1,429,Placebo,60,末次就医,3个月安慰剂,首次心血管事件的发生,危险下降(%),p,阿卡波糖(n=682),安慰剂(n=686),患者例数,有利于阿卡波糖,有利于安慰剂,冠心病心梗11291心绞痛51255血管重建112039心血管死亡1245充血性心衰脑血管意外/卒中2444外周血管病变11任何预先指定的心血管事件153249,0.02260.13440.18060.62980.50610.92550.0326,心血管事件,累计发生率(%),随机化后时间（年）,阿卡波糖,安慰剂,5,4,3,2,1,0,心血管事件发生率(仅指首次事件),血糖紊乱与心血管病变高血糖的分类高血糖与心血管病变血糖调节紊乱与心血管病变糖尿病心血管病变应激性高血糖与心血管病变血糖外的因素与心血管病变,内容,糖尿病对心血管死亡率的影响,美国第一次营养调查和二次营养调查冠心病死亡率的比较,糖尿病是冠心病的等位症,0,1,2,3,4,5,6,7,8,0,20,40,60,80,100,NodiabetesandnopreviousMI(n=1,304)DiabetesandnopreviousMI(n=890)NodiabetesandpreviousMI(n=69)DiabetesandpreviousMI(n=169),Survival(%),Year,HaffnerSM,etal.NEnglJMed1998;339:229234.,MI:myocardialinfarctionErrorbarsindicate95%CI,Allothercauses,2型糖尿病的死因分析(VeronaDiabetesStudy;DeMarcoetal,DiabetesCare22:756,1999),27.3,7.4,Malignancies,N=7148,10-yrfollow-up(1986-1995),NorhammarAetal.Lancet2002,急性心肌梗塞患者的糖代谢状态,因急性心肌梗塞而入住CCU的181例瑞典患者,出院后3个月糖耐量减退和未被诊断糖尿病的比例保持不变,35%有糖耐量减退（IGT）31%有未被诊断的糖尿病,平均年龄63.5岁此前未诊断糖尿病血糖11.1mmol/L,糖尿病是心血管疾病,A.H.A.ScientificStatement(Circulation1999;100:1134-1146),大血管病变的独立危险因子（UKPDS),UKPDS研究中心梗与不同治疗间的关系,CvGvIp=0.66,血糖紊乱与心血管病变高血糖的分类高血糖与心血管病变血糖调节紊乱与心血管病变糖尿病心血管病变应激性高血糖与心血管病变血糖外的因素与心血管病变,内容,Survivalrateinwomenbyplasmaglucosequartiles12and34(P=0.03).,5.40.5,7.51.5,DiabetesCare24:1634-1639,2001,AdmissionPlasmaGlucoseisAnindependentriskfactorinnondiabeticwomenaftercoronaryarterybypassgrafting,DIGAMIStudy(DiabetesMellitusInsulinGlucoseInfusioninAcuteMyocardialInfarction),Subject620patientswithdiabetesmellitusandacutemyocardialinfarctionIntensivetreatment:Standardtreatmentplusinsulin-glucoseinfusionforatleast24hoursfollowedbymultidoseinsulintreatment(306patients)Control:Standardtreatment(314patients),StudyDesign,InsulinTreatment,Insulintreatment:IntensiveControlpAtdischarge266(87%)135(43%)0.00013month245(80%)141(45%)0.0001Oneyear220(72%)141(49%)0.0001Othertreatment:nodifference,IntensiveControlPGlucoseat(mmol/l)Baseline15.7(4.2)15.4(4.1)0.424hafterrandomisation11.7(4.1)9.6(3.3)0.0001Glucoseathospitaldischarge9.0(3.0)8.2(3.1)0.01HaemoglobinA1c(%)Baseline8.0(2.0)8.2(1.9)0.23month1.1(1.6)0.4(1.5)215mg/dL(12mmol/L)Keyhypothesis:Hyperglycaemia(110mg/dL,6.1mmol/L)predisposestospecificICUcomplications,prolongedintensivecaredependency,anddeath,VandenBergheGetal.NEnglJMed2001:345:1359-1367,Prospective,randomised,controlledtrial,AllmechanicallyventilatedpatientsadmittedtoICUConsentfromclosestfamilymemberStratifiedforon-admissiondiagnosisandrandomisedto:,IntensiveinsulintreatmentGlucose110mg/dL,maintainat80110(atICUdischarge:conventionalapproach200mg/dL),ConventionalinsulintreatmentGlucose215mg/dL,maintainat180200,Studydesign,ProtocolStandardfeedingregimenstartedonadmissionInsulinbycontinuousi.v.infusion(syringepump)Wholebloodglucosemonitoredevery1to4hoursInsulindoseadjustedbyICUnursesandastudyphysiciannotinvolvedinclinicaldecisionmakingPrimaryoutcomemeasureDeathfromanycauseinICU(causeofdeathconfirmedbyautopsy-blindedpathologist)SecondaryoutcomemeasuresIn-hospitalmortality,VandenBergheGetal.NEnglJMed2001:345:1359-1367,Studydesign,Secondaryoutcomemeasures:morbidityBloodstreaminfections*Inflammation*Acuterenalfailureandneedfordialysis/haemofiltration*Anaemiaandneedforred-celltransfusions*Hyperbilirubinaemia*CriticalillnesspolyneuropathybyweeklyEMGscreening*Prolonged(14days)mechanicalventilationandICUstayCosts(cumulativeTISS),*Byblindedinvestigators.,VandenBergheGetal.NEnglJMed2001:345:1359-1367,Dataanalysis,Intention-to-treatanalysisThreemonthlyinterimanalysesofprimaryoutcome(deathsduringintensivecare)Studyterminatedforethicalreasons:significantlyreducedICUmortalityat1year(N=1548),VandenBergheGetal.NEnglJMed2001:345:1359-1367,Studypopulationatbaseline,0.9,Male,71%,71%,0.08,Age(y),6214,6314,First24hAPACHEIIscore,9(713),9(713),0.4,First24hTISSscore,43(3647),43(3746),0.7,Malignancy,15%,16%,0.7,0.1,BMI(kg/m2),25.84.7,26.24.4,0.9,Pre-admissiondiabetes,13%,13%,On-admissionglycaemia200mg/dL,12%,11%,0.2,Conventional(n=783),Intensive(n=765),Pvalue,Insulintreatment,Noncardiacsurgerytypeofillness,37%,38%,0.8,VandenBergheGetal.NEnglJMed2001:345:1359-1367,Bloodglucosecontrol,Conventional,Intensive,Pvalue,(n=783),(n=765),Patientsreceivinginsulin,39%,99%,0.0001,Meandailyinsulindose,whengiven(IU/d),33,71,0.0001,Durationofinsulinrequirement(%ICUstay),67,100,0.0001,Insulintreatment,VandenBergheGetal.NEnglJMed2001:345:1359-1367,Bloodglucosecontrol,Conventional,Intensive,DaysinICU,Bloodglucose(mg/dL),P14days,*,Dialysis/haemofiltration,*,Bloodstreaminfections,*,Antibiotics10days,*,Criticalillnesspolyneuropathy,46,28,35,17,41,29,44,4,37,22,27,23,*P0.01P0.0001Errorbars:95%confidenceintervals,VandenBergheGetal.NEnglJMed2001:345:1359-1367,Insulindoseorglycaemiccontrol?,MultivariatelogisticregressionanalysisofeffectonICUmortality:(correctedforallunivariatedeterminantsofoutcome)OR95%CIP-valueDailyinsulindose:1.0061.0021.0000.005(peraddedunit)Meanbloodglucoselevel:1.0151.0091.021150mg/dL,5days(N=451),VandenBergheGetal.CritCareMed2002:Inpress,5489,90125,126161,162197,198232,Bloodglucoselevel(mg/dL),2,18,4,6,8,10,12,14,16,Riskofcriticalillnesspolyneuropathy(%),Rho=1.0P30kg/m2微量白蛋白尿20微克/分或白蛋白/肌肝30mg/g,NCEP-ATPIII确定代谢综合征的指标,具备下列3个或更多指标l空腹血糖110mg/dll血压130/85mmHgl甘油三酯150mg/dllHDL-C男性102cm，女性88cm,CardiovascularDiseaseMortality,代谢综合症:总死亡率和心血管病死亡率KuopioHeartStudy,Lokka,H-M,etalJAMA2002;288:2709-2716,All-CauseMortality,CumulativeHazard(%),RRindicatesrelativerisk;CI,confidenceinterval.Medianfollow-up(range)forsurvivorswas11.6(9.1-19.7)years,No.atRiskMetabolicSyndrome,Yes866852834292No288279234100,Yes866852834292No288279234100,Follow-up,g,Follow-up,g,RR(85%CI)2.13(1.64-3.61),RR(85%CI)3.55(1.96-6.43),MetabolicSyndrome,Yes,No,MetabolicSyndrome,Yes,No,死亡四重奏“DeadlyQuartet”的影响搭桥手术后随访,Sprecher,etalJACC2000;36:1159-1165,No.ofRiskFactors,Male,Female,Years,1.0,Survival,0.9,0.8,0.7,0.6,0.5,0,1,2,3,4,5,6,7,8,9,10,0,1,2,3,4,No.ofRiskFactors,Years,1.0,Survival,0.9,0.8,0.7,0.6,0.5,0,1,2,3,4,5,6,7,8,9,10,0,1,2,3,4,DeadlyQuartetRiskFactors=obesity,diabetes,hypertension,hypertriglyceridemia,糖尿病并发症的病因和危险因素和,微血管病变眼睛肾脏神经,大血管病变缺血性心脏病中风周围血管病变,足,吸烟,ARB,2002,Steno-2研究：2型糖尿病患者多因素干预与心血管疾病研究,Steno-2研究,目的,对有微量白蛋白尿的2型糖尿病患者进行8年多的研究，比较包括行为和药物干预在内的强化多因素达标治疗与常规治疗对心血管疾病的影响,Steno-2研究,169位有微量白蛋白尿的2型糖尿病患者,9名患者因C肽6.5%,使用口服药当口服药使用至极量而HbA1c7.0%，开始使用胰岛素,强化治疗组降糖药物治疗,BMI25,开始使用二甲双胍（极量1gbid),开始使用格列奇特(极量160mgbid),格列奇特二甲双胍,二甲双胍格列奇特,强化组患者经饮食运动后HbA1c6.5,加用睡前NPH停二甲双胍,加用睡前NPH停格列奇特,使用每日多次胰岛素治疗,