胰岛素抵抗、糖尿病与冠心病(英文)课件

1、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、糖尿病与冠心病（英文）胰岛素抵抗、糖尿病与冠心病（英文）第1页，共29页。Adapted from World Health Organization. Definition, Diagnosis and Classification of Diabetes Mellitus and its Complications. G

2、eneva: 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、糖尿病与冠心病（英文）胰岛素抵抗、糖尿病与冠心病（英文）第3页，共29页

3、。Hospitalization Costs for Chronic Complications of Diabetes in the USAmerican Diabetes Association. Economic Consequences of Diabetes Mellitusin the US in 1997. Alexandria, VA: American Diabetes Association, 1998:1-14.Total costs 12 billion US $CVD accounts for 64% of total costsOthersOphthalmic di

4、seaseCardiovasculardiseaseRenal 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、糖尿病与冠心病（英文）胰岛素抵抗、糖尿病与冠心病（英文）第4页，共29页。Annual CHD Deaths per 1000 PersonsKannel WB, McGee DL. JAMA 1979;241:2035-2038.Framingham Study: DM and CHD Mortality20-Year Follow-up178174M

5、enWomenDMNon-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、糖尿病与冠心病（英文）胰岛素抵抗、糖尿病与冠心病（英文）第5页，共29页。Ischemicheartdisease% of DeathsGeiss LS et al. In: Diabetes in America. 2nd ed. 1995; chap 11.Mortality in People with DiabetesCauses of DeathOtherheartdiseaseDiabetesCancerStrokeInfectionOther膘既请监科亭兵遗剧疟赚熟踊哮仲吟披

6、郎琴淀炳铀孰肚糟迭绝镑敌偶芭涕胰岛素抵抗、糖尿病与冠心病（英文）胰岛素抵抗、糖尿病与冠心病（英文）第6页，共29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)29.919.2MenWomenDiabetesNo DiabetesAll heart diseaseIschemic hea

7、rt 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、糖尿病与冠心病（英文）胰岛素抵抗、糖尿病与冠心病（英文）第7页，共29页。NondiabetesDiabetes *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 Rate

8、s for Ischemic Heart Disease in NHANES Subjects with and without Diabetes*17.06.8-16.6%+10.7%Men, cohort 1*Men, cohort 2*Women, cohort 1*Women, cohort 2*-43.8%-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 diabetes

9、DiabetesTwo 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、糖尿病与冠心病（英文）胰岛素抵抗、糖尿病与冠心病（英文）第11页，共29页。Putative Mechanism for Increased Atherosclerosis in Type 2 DiabetesBLACK BOXDyslipidemiaHypertensionHyperinsulinemia/insulin resistanceHemostatic abnormalitiesHyperglycemiaAGE proteinsOxidative stressAGE = ad

10、vanced 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、糖尿病与冠心病（英文）胰岛素抵抗、糖尿病与冠心病（英文）第12页，共29页。 + = moderately increased compared with nondiabetic population+ = markedly increased compared with nondiabetic population = not differ

11、ent compared with nondiabetic populationPrevalence of Cardiovascular Risk Factors in Diabetic Subjects Relative to NondiabeticsType 1Dyslipidemia Hypertriglyceridemia Low HDL Small, dense LDL Increased apo BHypertensionHyperinsulinemia/insulin resistanceCentral obesityFamily history of atheroscleros

12、isCigarette smokingAdapted from Chait A, Bierman EL. In: Joslins Diabetes Mellitus. Philadelphia: Lea & Febiger, 1994:648-664.Type 2Risk 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、糖尿病与冠心病（英文）胰岛素抵抗、糖尿病与冠心病（英文）第13页，共29页。Differences in HDL Cholesterol and LDL Size by Diabetic Status in Women and MenH

13、oward BV et al. Diabetes Care 1998; 21:1258-1265.0-2-4-6-8Differences between participants with and without diabetesHDL CholesterolLDL Size0-2-4-6-8mg/dLWomenMenWomenMen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、糖尿病与冠心病（英文）胰岛素抵抗、糖尿病与冠心病（英文）第14页，共29页。Strategies for Reduction of Diabetic ComplicationsMicro

14、vascular complications- Aggressive screening- Improved metabolic controlMacrovascular 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 car

15、diovascular 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、糖尿病与冠心病（英文）胰岛素抵抗、糖尿病与冠心病（英文）第15页，共29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

16、 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16页，共29页。Incidence Rates of MI and Microvascular Endpoints by Mean Hemoglobin A1c: UKPDS567891011Incidence per 1000 Person Years (%)St

17、ratton 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、糖尿病与冠心病（英文）胰岛素抵抗、糖尿病与冠心病（英文）第17页，共29页。Plasma Insulin and Triglycerides Predict Ischemic Heart Di

18、sease: 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、糖尿病与冠心病（英文）胰岛素抵抗、糖尿病与冠心病（英文）第18页，共29页。Plasma Insulin and Apolipoprotein B Pr

19、edict Ischemic Heart Disease: Quebec Cardiovascular 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仇湘嫂暴陵捞吞筐霄

20、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20页，共29页。Baseline Anthropometric Variables and Cardiovascular Risk Factors in Subjects with Normal Glucose Tolerance at Baseline According to Conversion Status at 8-Year Follow-up: San Antonio Heart StudyBMI (kg/m2)Centrality*TG (mmol)HDLC (mmol)SBP (mmHg)Fasti

21、ng 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)Norm

22、al (n=490)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、糖尿病与冠心病（英文）胰岛素抵抗、糖尿病与冠心病（英文）第21页，共29页。“Ticking Clock” HypothesisWHO. Diabetologia 1985;28:615-640; Haffner SM et al. JAMA 1990;263:2893-2898.ForMicrovascular complicationsMacrovascular complicationsThe “clock

23、 starts ticking”At onset of hyperglycemiaBefore the diagnosis of hyperglycemia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、糖尿病与冠心病（英文）胰岛素抵抗、糖尿病与冠心病（英文）第22页，共29页。Hemoglobin A1Fasting GlucoseThe 7-Year Age-Adjusted Incidence of CHD Mortality and All CHD Events: East-West StudyLehto S et al. Diabetes 1997;46:

24、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、糖尿病与冠心病（英文）胰岛素抵抗、糖尿病与冠心病（英文）第23页，共29页。Stepwise Selection of Risk Factors* in 2693 White Patients with Type 2 Diabetes with D

25、ependent Variable as Time to First Event: UKPDS VariableLow-Density Lipoprotein CholesterolHigh-Density Lipoprotein CholesterolHemoglobin A1cSystolic Blood PressureSmokingP Value0.0001 0.0001 0.0022 0.00650.056Coronary Artery Disease (n=280)Position in ModelFirstSecondThirdFourthFifth*Adjusted for a

26、ge 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、糖尿病与冠心病（英文）胰岛素抵抗、糖尿病与冠心病（英文）第24页，共29页。Criteria for Accepting Cardiovascular Risk Factor Management as Similar in Diabetic and CHD SubjectsThe risk of vascular disease is similar in diabetic subjects without pre-ex

27、isting vascular disease as in nondiabetic subjects with vascular diseaseGlycemia alone will not completely eliminate the excess of CHD risk in diabetic subjectsLipid 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、糖尿病与冠心病

28、（英文）胰岛素抵抗、糖尿病与冠心病（英文）第25页，共29页。Incidence of Fatal or Nonfatal MI During a 7-Year Follow-up in Relation to History of MI in Nondiabetic vs Diabetic Subjects: East-West StudyIncidence During Follow-up (%)(n=69)Nondiabetics with prior MINondiabetics with no prior MIDiabetics with prior MIDiabetics with

29、 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、糖尿病与冠心病（英文）胰岛素抵抗、糖尿病与冠心病（英文）第26页，共29页。Incidence of Fatal or Nonfatal Stroke During a 7-Year Follow-up in Relation to History of MI