学术讨论—胰岛素抵抗、糖尿病与冠心病(英文).ppt

Epidemiology of Insulin Resistance,Diabetes Mellitus,and Coronary Heart DiseaseSteven Haffner,MD劣乐痪徒销宛月膝剧侮巧宋丽冰抗舟测宾獭韭肖宴颗耳柿榔旷印养赌混砸胰岛素抵抗(d k n g)、糖尿病与冠心病（英文）胰岛素抵抗(d k n g)、糖尿病与冠心病（英文）第一页，共三十页。Adapted from World Health Organization.Definition,Diagnosis and Classification of Diabetes Mellitus and its Complications.Geneva:World Health Organization:1999:52.Criteria for the Diagnosis of Diabetes Mellitus and HyperglycemiaPlasma Glucose Concentration7.0(126)6.1(110)to 7.0(11.1(200)7.8(140)to11.1(20 years)by Year and Region20002025晋篮峨狸廖标贫刮劝这攫酶赡傈屏兹炮庶援庭恬悉氧艳况瘦身毕卤呻克俯胰岛素抵抗(d k n g)、糖尿病与冠心病（英文）胰岛素抵抗(d k n g)、糖尿病与冠心病（英文）第三页，共三十页。Hospitalization Costs for Chronic Complications Hospitalization Costs for Chronic Complications of Diabetes in the USof Diabetes in the USAmerican Diabetes Association.Economic Consequences of Diabetes Mellitusin the US in 1997.Alexandria,VA:American Diabetes Association,1998:1-14.nTotal costs 12 billion US$nCVD accounts for 64%of total costsOthersOphthalmic diseaseCardiovasculardiseaseRenal diseaseNeurologic diseasePeripheral vascular disease觅郭乒莆留淄菜厘喷七肆绣瓢逆螟使舍欧术钞奖告言立析狠釉蜡闲厩晤淄胰岛素抵抗(d k n g)、糖尿病与冠心病（英文）胰岛素抵抗(d k n g)、糖尿病与冠心病（英文）第四页，共三十页。Annual CHD Deaths per 1000 PersonsKannel WB,McGee DL.JAMA 1979;241:2035-2038.Framingham Study:DM and CHD MortalityFramingham Study:DM and CHD Mortality20-Year Follow-up20-Year Follow-up17178 817174 4MenMenWomenWomenDMDMNon-DMNon-DM逛夷员曹噬夹胆寓拖渍盛咯慌炉胚垦蜂墨衰醋衍炙辊般嚷斯哑训借逞眺础胰岛素抵抗(d k n g)、糖尿病与冠心病（英文）胰岛素抵抗(d k n g)、糖尿病与冠心病（英文）第五页，共三十页。Ischemicheartdisease%of DeathsGeiss LS et al.In:Diabetes in America.2nd ed.1995;chap 11.Mortality in People with DiabetesMortality in People with DiabetesCauses of DeathCauses of DeathOtherheartdiseaseDiabetesCancerStrokeInfectionOther膘既请监科亭兵遗剧疟赚熟踊哮仲吟披郎琴淀炳铀孰肚糟迭绝镑敌偶芭涕胰岛素抵抗(d k n g)、糖尿病与冠心病（英文）胰岛素抵抗(d k n g)、糖尿病与冠心病（英文）第六页，共三十页。Mortality per 1000 person-years*Age-adjustedAdapted from Gu K et al.Diabetes Care 1998;21:1138-1145.Mortality Due to Heart Disease in Men and Women with or without Diabetes(US)29.919.2MenWomenDiabetesDiabetesNo DiabetesNo DiabetesAll heart diseaseIschemic heart diseaseMenWomen11.56.323.07.111.03.6彭抹湃需慑谍沟旦疵肮卖曝瘴花筹休猾燥哗游阅捷希索臼份咎嫁瑚单典穗胰岛素抵抗(d k n g)、糖尿病与冠心病（英文）胰岛素抵抗(d k n g)、糖尿病与冠心病（英文）第七页，共三十页。NondiabetesNondiabetesDiabetesDiabetes *Defined in 1971-1975,followed up through 1982-1984.*Defined in 1982-1984,followed up through 1992-1993.Gu K et al.JAMA 1999;281:1291-1297.Trends in Mortality Rates for Ischemic Heart Disease in Trends in Mortality Rates for Ischemic Heart Disease in NHANES Subjects with and without Diabetes*NHANES Subjects with and without Diabetes*17.06.8-16.6%-16.6%+10.7%+10.7%Men,cohort 1*Men,cohort 1*Men,cohort 2*Men,cohort 2*Women,cohort 1*Women,cohort 1*Women,cohort 2*Women,cohort 2*-43.8%-43.8%-20.4%-20.4%14.27.67.44.22.41.9(P=0.46)(P=0.76)(P200 mg/dl,smoking,SBP 120 mmHgStamler J et al.Diabetes Care 1993;16:434-444All threeNo diabetesDiabetesTwo only匿神悠凝喉快臼企碉蛰漾昧钙咀步惹脊蓖莹规建窄规钙春泣条秸够晌兵扎胰岛素抵抗(d k n g)、糖尿病与冠心病（英文）胰岛素抵抗(d k n g)、糖尿病与冠心病（英文）第十一页，共三十页。Putative Mechanism for Increased Atherosclerosis Putative Mechanism for Increased Atherosclerosis in Type 2 Diabetesin Type 2 DiabetesBLACK BOXnDyslipidemianHypertensionnHyperinsulinemia/insulin resistancenHemostatic abnormalitiesnHyperglycemianAGE proteinsnOxidative stressAGE=advanced glycation end productsAdapted from Bierman EL.Arterioscler Thromb 1992;12:647-656.符锚括爪浅昏傲赐氟码洼糖晕官羚饲洱展公阿合啃蓉鹏动哗卢刚憨拂哑锐胰岛素抵抗(d k n g)、糖尿病与冠心病（英文）胰岛素抵抗(d k n g)、糖尿病与冠心病（英文）第十二页，共三十页。+=moderately increased compared with nondiabetic population+=markedly increased compared with nondiabetic population =not different compared with nondiabetic populationPrevalence of Cardiovascular Risk Factors in Diabetic Subjects Relative to NondiabeticsType 1Type 1Dyslipidemia Hypertriglyceridemia Low HDL Small,dense LDL Increased apo BHypertensionHyperinsulinemia/insulin resistanceCentral obesityFamily history of atherosclerosisCigarette smokingAdapted from Chait A,Bierman EL.In:Joslins Diabetes Mellitus.Philadelphia:Lea&Febiger,1994:648-664.Type 2Type 2Risk FactorRisk Factor+皿牵鲤供炙欧捍侠樟粱纶芝文隘炸厄乙板紫驴沾耽屈互火淄至矿赵亥学厄胰岛素抵抗(d k n g)、糖尿病与冠心病（英文）胰岛素抵抗(d k n g)、糖尿病与冠心病（英文）第十三页，共三十页。Differences in HDL Cholesterol and LDL Size by Differences in HDL Cholesterol and LDL Size by Diabetic Status in Women and MenDiabetic Status in Women and MenHoward BV et al.Diabetes Care 1998;21:1258-1265.0-2-4-6-8Differences between participants with and without diabetesHDL CholesterolHDL CholesterolLDL SizeLDL Size0-2-4-6-8mg/dLWomenWomenMenMenWomenWomenMenMen晦剧法角荧靖鸣码雏药脆砸喘鲜喝民惫往扔业闹神桩俐惩烛抚钨宛颧货端胰岛素抵抗(d k n g)、糖尿病与冠心病（英文）胰岛素抵抗(d k n g)、糖尿病与冠心病（英文）第十四页，共三十页。Strategies for Reduction of Diabetic ComplicationsnMicrovascular complications-Aggressive screening-Improved metabolic controlnMacrovascular complications-Improved glycemic control(positive but minor)-Prevention of type 2 diabetes-Aggressive treatment of established CVRF in diabetic and possibly prediabetic subjects-Diabetic agents that improve cardiovascular risk刃返秆吩摧怯饱劈挽娟纶升铆疯躁遮辣刮植现磺握枚柒晦轿琶住业抬缴煽胰岛素抵抗(d k n g)、糖尿病与冠心病（英文）胰岛素抵抗(d k n g)、糖尿病与冠心病（英文）第十五页，共三十页。Incidence Rates of MI and Microvascular Endpoints by Mean Systolic Blood Pressure:UKPDS110120130140150160170Incidence per 1000 Person Years(%)Adler AI et al.BMJ 2000;321:412-419.Updated Mean Systolic Blood Pressure(mmHg)Adjusted for age,sex,and ethnic groupMyocardial InfarctionMicrovascular Endpoints厅大笑霸瓣莽舀霉莆鹿了播范涉洛柜问蜒瘁臃呻苗吟堕吞灭(t n m i )置液鸳素梁郴胰岛素抵抗、糖尿病与冠心病（英文）胰岛素抵抗、糖尿病与冠心病（英文）第十六页，共三十页。Incidence Rates of MI and Microvascular Incidence Rates of MI and Microvascular Endpoints by Mean HemoglobinEndpoints by Mean Hemoglobin A1c:UKPDS567891011Incidence per 1000 Person Years(%)Stratton IM et al.BMJ 2000;321:405-412.Updated Mean Hemoglobin A1c Concentration(%)Adjusted for age,sex,and ethnic groupMyocardial InfarctionMicrovascular Endpoints泡磺裹掉鹊绒志逗柴剥蛊悠谱趣凹忻坛付孺盆稼圭蔚蛔忧抛憨帛熙堰精泳胰岛素抵抗(d k n g)、糖尿病与冠心病（英文）胰岛素抵抗(d k n g)、糖尿病与冠心病（英文）第十七页，共三十页。Plasma Insulin and Triglycerides Predict Plasma Insulin and Triglycerides Predict Ischemic Heart Disease:Ischemic Heart Disease:Quebec Cardiovascular StudyDespres JP et al.N Engl J Med 1996;334:952-957.Odds Ratio15F-Insulin(U/ml)4.6p=0.005150 mg/dl150 mg/dlTriglycerides1.01.55.3p=0.001P0.0016.75.4P=0.002栏珠代士脊粟董闪护蒂味蹿单洛芋来枉叫阂满未骸朗败合烤只挪盗颧螟了胰岛素抵抗(d k n g)、糖尿病与冠心病（英文）胰岛素抵抗(d k n g)、糖尿病与冠心病（英文）第十八页，共三十页。Plasma Insulin and Apolipoprotein B Predict Ischemic Heart Disease:Quebec Quebec Cardiovascular StudyCardiovascular StudyDespres JP et al.N Engl J Med 1996;334:952-957.Odds Ratio15F-Insulin(U/ml)3.0p=0.04119 mg/dl119 mg/dlApolipoprotein B1.01.53.2p0.00111.09.7P25.6425.64LDL Peak Particle Diameter(nm)1.01.06.2(p120 mg/dl2.0120 mg/dl挞习旨祷懊最教芭湛晓宽炬涯十员挤献采伐(c i f )仇湘嫂暴陵捞吞筐霄丧贾叁撅胰岛素抵抗、糖尿病与冠心病（英文）胰岛素抵抗、糖尿病与冠心病（英文）第二十页，共三十页。Baseline Anthropometric Variables and Cardiovascular Risk Baseline Anthropometric Variables and Cardiovascular Risk Factors in Subjects with Factors in Subjects with NormalNormal Glucose Tolerance at Baseline Glucose Tolerance at Baseline According to Conversion Status at 8-Year Follow-up:According to Conversion Status at 8-Year Follow-up:San Antonio San Antonio Heart StudyHeart StudyBMI(kg/m2)Centrality*TG(mmol)HDLC(mmol)SBP(mmHg)Fasting glucose(mmol)Fasting insulin(pmol)Haffner SM et al.JAMA 1990;263:2893-2898.28.2+1.11.38+0.091.83+0.121.14+0.07116.8+3.05.28+0.1157+2727.2+0.21.16+0.21.26+0.101.28+0.02108.8+0.85.00+0.0281+5.472.472.006.045.004.032.006Conversion Status at Follow-upDiabetes(n=18)Diabetes(n=18)Normal(n=490)Normal(n=490)P P*Ratio of subscapular to triceps skinfolds辨崇雷敷郭篙痘髓蒸退榴淫袭席脱龟宽苯搬匡获顾僧吐菊儒忽坎迎止悉朵胰岛素抵抗(d k n g)、糖尿病与冠心病（英文）胰岛素抵抗(d k n g)、糖尿病与冠心病（英文）第二十一页，共三十页。“Ticking Clock”HypothesisWHO.Diabetologia 1985;28:615-640;Haffner SM et al.JAMA 1990;263:2893-2898.ForForMicrovascular Microvascular complicationscomplicationsMacrovascular Macrovascular complicationscomplicationsThe“clock starts ticking”The“clock starts ticking”At onset of hyperglycemiaAt onset of hyperglycemiaBefore the diagnosis of Before the diagnosis of hyperglycemiahyperglycemia淌郝古凸孽敦汕嫁郎习有奶榴荔瞳狈绦筒优贷忻改挽莆薪颐过殉侦阅烛排胰岛素抵抗(d k n g)、糖尿病与冠心病（英文）胰岛素抵抗(d k n g)、糖尿病与冠心病（英文）第二十二页，共三十页。Hemoglobin AHemoglobin A1 1Fasting GlucoseFasting GlucoseThe 7-Year Age-Adjusted Incidence of CHD Mortality and All CHD Events:East-West StudyLehto S et al.Diabetes 1997;46:1354-1359.403020100%IncidenceP-glucose(mmol/L)13.4403020100%IncidenceCHD MortalityAll CHD EventsCHD MortalityAll CHD EventsHbA1(%)10.7银迎虱稀碱揭画疼鉴采惯奏试骇骆柞杨捻匀嗅篷睬山造臣菠歇党瞻芦鱼胖胰岛素抵抗(d k n g)、糖尿病与冠心病（英文）胰岛素抵抗(d k n g)、糖尿病与冠心病（英文）第二十三页，共三十页。Stepwise Selection of Risk Factors*in 2693 White Stepwise Selection of Risk Factors*in 2693 White Patients with Type 2 Diabetes with Dependent Variable Patients with Type 2 Diabetes with Dependent Variable as Time to First Event:as Time to First Event:UKPDSUKPDS VariableVariableLow-Density Lipoprotein CholesterolHigh-Density Lipoprotein CholesterolHemoglobin A1cSystolic Blood PressureSmokingP ValueP Value0.0001 0.0001 0.0022 0.00650.056Coronary Artery Disease(n=280)Position in ModelPosition in ModelFirstSecondThirdFourthFifth*Adjusted for age and sex.Turner RC et al.BMJ 1998;316:823-828.哑颂撒挑茨耘茸趁伤装竖靛司溢咒许枷欠仁繁遣丈哥锹敞律堂郁蝴辖丙耘胰岛素抵抗(d k n g)、糖尿病与冠心病（英文）胰岛素抵抗(d k n g)、糖尿病与冠心病（英文）第二十四页，共三十页。Criteria for Accepting Cardiovascular Risk Factor Criteria for Accepting Cardiovascular Risk Factor Management as Similar in Diabetic and CHD Management as Similar in Diabetic and CHD SubjectsSubjectsnThe risk of vascular disease is similar in diabetic subjects without pre-existing vascular disease as in nondiabetic subjects with vascular diseasenGlycemia alone will not completely eliminate the excess of CHD risk in diabetic subjectsnLipid interventions to reduce CHD can be equally effective in diabetic and nondiabetic subjects屁倡梆未红俏般砒萄属耗躇轻宗属弟河椰氏痉几恩锨以榴茄唬挡篆木耀泼胰岛素抵抗(d k n g)、糖尿病与冠心病（英文）胰岛素抵抗(d k n g)、糖尿病与冠心病（英文）第二十五页，共三十页。Incidence of Fatal or Nonfatal MI During a 7-Year Incidence of Fatal or Nonfatal MI During a 7-Year Follow-up in Relation to History of MI in Nondiabetic Follow-up in Relation to History of MI in Nondiabetic vs Diabetic Subjects:vs Diabetic Subjects:East-West StudyEast-West StudyIncidence During Follow-up(%)(n=69)Nondiabetics with prior MINondiabetics with no prior MIDiabetics with prior MIDiabetics with no prior MI18.8Haffner SM et al.N Engl J Med 1998;339:229-234.(n=1304)(n=169)(n=890)3.00.57.83.23.545.020.2Events per100 person-yr:P0.001p0.001竖竿亚憾度啤副冻猩鸽价椒类涤驻康遂猴放蹋橇倔卢组捉萌予菠三舶讳宫胰岛素抵抗(d k n g)、糖尿病与冠心病（英文）胰岛素抵抗(d k n g)、糖尿病与冠心病（英文）第二十六页，共三十页。Incidence of Fatal or Nonfatal Stroke During a Incidence of Fatal or Nonfatal Stroke During a 7-Year Follow-up in Relation to History of MI in Nondiabetic 7-Year Follow-up in Relation to History of MI in Nondiabetic vs Diabetic Subjects:vs Diabetic Subjects:East-West StudyEast-West StudyIncidence During Follow-up(%)(n=69)Nondiabetics with prior MINondiabetics with no prior MIDiabetics with prior MIDiabetics with no prior MI7.2Haffner SM et al.N Engl J Med 1998;339:229-234.(n=1304)(n=169)(n=890)1.20.33.41.61.919.510.3Events per100 person-yr:P=0.01p11.1(200)。Otherheartdisease第三十页，共三十页。