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1、控制糖尿病患者心血管危险的干预治疗策略,糖尿病与心血管危险影响心血管危险的因素综合控制的理论与实践,Countries With Highest Numbers of EstimatedCases of Diabetes for 2000 and 2030,Ranking,Country,People with diabetes(millions),Country,People with diabetes(millions),2000,2030,1India31.7India79.42China20.8China42.33U.S.17.7U.S.30.34Indonesia8.4Indones
2、ia21.35Japan6.8Pakistan13.96Pakistan5.2Brazil11.37Russian Federation4.6Bangladesh11.18Brazil4.6Japan8.99Italy4.3Pinecones7.810Bangladesh3.2Egypt16.7,Total:177 million,366 MILLION BY 2030,Type 2 diabetes and CHD7-Year Incidence of Fatal/Nonfatal MI(East West Study),Incidence During Follow-up(%),(n=69
3、),Nondiabetics with prior MINondiabetics with no prior MIDiabetics with prior MIDiabetics with no prior MI,18.8,Haffner SM et al.N Engl J Med 1998;339:229-234.,(n=1304),(n=169),(n=890),3.0,0.5,7.8,3.2,3.5,45.0,20.2,Events per100 person-yr:,P0.001,p0.001,Type 2 diabetes and Stroke7-Year Incidence of
4、Fatal/Nonfatal Stroke(East West Study),Incidence During Follow-up(%),(n=69),Nondiabetics with prior MINondiabetics with no prior MIDiabetics with prior MIDiabetics with no prior MI,7.2,Haffner SM et al.N Engl J Med 1998;339:229-234.,(n=1304),(n=169),(n=890),1.2,0.3,3.4,1.6,1.9,19.5,10.3,Events per10
5、0 person-yr:,P=0.01,p0.001,Prevalence of CHD by the Metabolic Syndrome and Diabetes in the NHANES Population Age 50+,Alexander C et al.Diabetes 2003;52:1210-1214,25%,20%,15%,10%,5%,0%,No MS/No DM,8.7%,13.9%,7.5%,19.2%,MS/No DM,DM/No MS,DM/MS,%of population=54.2%28.7%2.3%14.8%,CHD Prevalence,Schillac
6、i G.JACC.2004;43:1817-1822,代谢综合征与心血管危险,Ml and Microvascular End Points:Incidence byMean Systolic BP and HbA1c Concentration,Ml,Microvascular and points,Ml,Microvascular and points,50,40,30,20,10,0,80,60,40,20,0,Adjusted incidence per 1000 person-yr(%),110,120,130,140,150,160,170,5,6,7,8,9,10,11,Upda
7、ted mean systolic BP(mmHg),Updated mean HbA1c concentration(%),Adjusted incidence per 1000 person-yr(%),Adler Al et al.BMJ 2000;321:412-419,Stration IM et al.BMJ 2000;321:405-412,MetS和DM患者血脂异常特征,游离脂肪酸TGHDL-C VLDL-C 小而密LDL颗粒氧化LDL-C 餐后高脂血症,Male,Gender-adjusted,Female,Reduced risk with small,dense LDL,
8、0.1,Relative risk for myocardial infarction,1,10,Increased risk with small,dense LDL,Small,dense LDL increases cardiovascular risk,UKPDS Stepwise Selection of Risk Factors*in Patients with Type 2 Diabetes,VariableLDL-CHDL-CHemoglobin A1cSystolic Blood PressureSmoking,P Value0.0001 0.0001 0.0022 0.00
9、650.056,Coronary Artery Disease(n=280),Position in ModelFirstSecondThirdFourthFifth,*Adjusted for age and sex.Turner RC et al.BMJ 1998;316:823-828.,Mangaging overweight in type 2 diabetics,Effective weight management is the first step in treating type 2 diabetes,Weight loss(kg)in first 12 months,Lea
10、n MEJ et al.,Diabet Med,1990;7:228-233,Weight loss is difficult to maintain by dietand exercise alone in type 2 diabetes,UKPDS 34.Lancet 1998;352:354,Insulin,Chlorpropamide,Gllbenclamide,Diet alone,Metformin,Weight change(kg),7,6,5,4,3,2,1,0,-1,0,2,4,6,8,10,Years from randomisation,Good glycemic con
11、trol is not enough,UKPDS,GOOD GLYCEMIC CONTROL,MICROVASCULAR COMPLICATIONSSignificant reductions,MACROVASCULAR COMPLICATIONSNo significant effect,PROACTIVE Study,Sept.2005,欧洲糖尿病会议,Pioglitazone vs Placebo,ACCORD StudyAction to Control Cardiovascular risk in Diabetes,Prisant LM.J Clin Pharmacol 2004;4
12、4(4):423-430,HbA1c:6.0%vs 7.0-7.9%,糖尿病患者降压治疗临床试验,SHEP ALLHAT SYST-EUR HOPE CAPPP HOT NORDIL RENAAL STOP-2 PRIME INSIGHT LIFE UKPDS,Major cardiovascular events(per 100 patients-years)in all treated hypertensive and in hypertensive patients with diabetes in relation to target blood pressures of 90.85,
13、and 80 mm Hg.,HOT Study:Results in Patients with DM,Effect of Intensive vs Moderate Antihypertensive Treatmenton Stroke Incidence in Diabetic Normotensives,IntensiveModerateAchieved BP(mmHg)128/75137/81Stroke(%)1.75.4,Schrier et al.,Kidney Int 2002;61:1086,CHD Prevention Trials with Statins in Diabe
14、tic Subjects Subgroup Analyses,Primary PreventionAFCAPS/TexCAPSSecondary PreventionCARE4SLIPID4S-Extended,CHD RiskReduction(overall),Drug,No.,LovastatinPravastatinSimvastatinPravastatinSimvastatin,43%25%(p=0.05)55%(p=0.002)19%42%(p=0.001),37%23%32%25%32%,239586202782483,CHD RiskReduction(diabetes),S
15、tudy,Adapted from Downs JR et al.JAMA 1998;279:1615-1622;Goldberg RB et al.Circulation 1998;98:2513-2519;Pyrl K et al.Diabetes Care 1997;20:614-620;The Long-Term Intervention with Pravastatin in Ischaemic Disease(LIPID)Study Group.N Engl J Med 1998;339:1349-1357;Haffner SM et al.Arch Intern Med 1999
16、;159:2661-2667.,CARDS:主要终点,年,安慰剂组事件数 127,立普妥组事件数 83,累积危险(%),0,5,10,15,0,1,2,3,4,4.75,P=0.001,Colhoun HM,Betteridge DJ,Durrington PN,et al.Lancet.2004;364:685-696.,37,Trials with Fibrates in Patients with Diabetes,FIELD StudyFenofibrate Intervention and Event Lowering in Diabetes,Mazzone T.Am J Cardi
17、ol 2004;93:27C-31C,糖尿病患者心血管危险因素的控制目标,减轻体重 降糖:HbA1c 7.0%降压:130/80 调脂:LDL-C 1.81 mmol/L,Steno-2 StudyMultifactorial Intervention and Cardiovascular Disease in Patients with Type 2 Diabetes,Grade P,et al.N ENGL J MED 2003;348:383-393,Steno-2:Intensive Therapy,NEJM 2000;342:905-912,Basic Intervention,脂肪
18、摄入30%饱和脂肪酸摄入10%运动 3035次/wACEI or ARB多种维生素Aspirin,Pharmacology Intervention,降糖 metformin gliclazide metformin+gliclazide降压 thiazide ACEI or ARB+CCB-blocker降脂 statins,Steno-2:Treatment Goals,Variable Conventional Intensive Therapy TherapySBP(mmHg)140 130 DBP(mmHg)85 80 Hba1c(%)6.5 6.5TC(mg/dl)190 175
19、TG(mg/dl)150 150,Steno-2 Change in Clinical Variables at the End of the Study,Variable Conventional Intensive p Therapy TherapySBP(mmHg)-33-142 0.001DBP(mmHg)-82-122 0.006 Carbohydrates(%)4.80.9 9.30.9 0.001,FPG(mg/dl)-1811-528 0.001 HbA1c(%)0.2 0.3-0.50.2 0.001 TC(mg/dl)-37-504 0.001 LDL-C(mg/dl)-1
20、36-475 0.001 TG(mg/dl)943-4114 0.015,Steno-2 Study:Composite End Point,Grade P et al.N Engl J Med 2003;348:383-393,Primary composite end point(%),60,50,40,30,20,10,0,0,12,24,36,48,60,72,84,96,Months of follow-up,Hazard ratio=0.47(95%Cl 0.24,0.73)P=0.008,Conventional Therapy,Intensive therapy,小 结,T2DM患者有多重心血管危险因素集聚，是心血管高危人群。T2DM治疗的主要目标应该转移到预防或延缓心血管病事件。在改善生活行为的同时，积极有效地实施降压、降脂和降糖综合措施，是控制糖尿病患者心血管危险的主要治疗策略。,
