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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 Estimated Cases of Diabetes for 2000 and 2030,Ranking,Country,People with diabetes (millions),Country,People with diabetes (millions),2000,2030,1 India 31.7 India 79.4 2 China 20.8 China 42.3 3 U.S. 17.7 U.S. 30.3
2、 4 Indonesia 8.4 Indonesia 21.3 5 Japan 6.8 Pakistan 13.9 6 Pakistan 5.2 Brazil 11.3 7 Russian Federation 4.6 Bangladesh 11.1 8 Brazil 4.6 Japan 8.9 9 Italy 4.3 Pinecones 7.8 10 Bangladesh 3.2 Egypt1 6.7,Total: 177 million,366 MILLION BY 2030,Type 2 diabetes and CHD 7-Year Incidence of Fatal/Nonfata
3、l MI (East West Study),Incidence During Follow-up (%),(n=69),Nondiabetics with prior MI Nondiabetics with no prior MI Diabetics with prior MI Diabetics 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 per 100 person-
4、yr:,P0.001,p0.001,Type 2 diabetes and Stroke 7-Year Incidence of Fatal/Nonfatal Stroke (East West Study),Incidence During Follow-up (%),(n=69),Nondiabetics with prior MI Nondiabetics with no prior MI Diabetics with prior MI Diabetics with no prior MI,7.2,Haffner SM et al. N Engl J Med 1998;339:229-2
5、34.,(n=1304),(n=169),(n=890),1.2,0.3,3.4,1.6,1.9,19.5,10.3,Events per 100 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,
6、DM/No MS,DM/MS,% of population = 54.2% 28.7% 2.3% 14.8%,CHD Prevalence,Schillaci G. JACC. 2004; 43:1817-1822,代谢综合征与心血管危险,Ml and Microvascular End Points: Incidence by Mean Systolic BP and HbA1c Concentration,Ml,Microvascular and points,Ml,Microvascular and points,50,40,30,20,10,0,80,60,40,20,0,Adjus
7、ted incidence per 1000 person-yr (%),110,120,130,140,150,160,170,5,6,7,8,9,10,11,Updated 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 TG HDL-C
8、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,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 Diabete
9、s,Variable LDL-C HDL-C Hemoglobin A1c Systolic Blood Pressure Smoking,P Value 0.0001 0.0001 0.0022 0.0065 0.056,Coronary Artery Disease (n=280),Position in Model First Second Third Fourth Fifth,*Adjusted for age and sex. Turner RC et al. BMJ 1998;316:823-828.,Mangaging overweight in type 2 diabetics
10、,Effective weight management is the first step in treating type 2 diabetes,Weight loss (kg) in first 12 months,Lean MEJ et al., Diabet Med, 1990;7:228-233,Weight loss is difficult to maintain by diet and exercise alone in type 2 diabetes,UKPDS 34. Lancet 1998;352:354,Insulin,Chlorpropamide,Gllbencla
11、mide,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 control is not enough,UKPDS,GOOD GLYCEMIC CONTROL,MICROVASCULAR COMPLICATIONS Significant reductions,MACROVASCULAR COMPLICATIONS No significant effect,PROACTIVE Study,Sept. 2005, 欧洲糖尿病
12、会议,Pioglitazone vs Placebo,ACCORD Study Action to Control Cardiovascular risk in Diabetes,Prisant LM. J Clin Pharmacol 2004; 44(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 pat
13、ients-years) in all treated hypertensive and in hypertensive patients with diabetes in relation to target blood pressures of 90. 85, and 80 mm Hg.,HOT Study: Results in Patients with DM,Effect of Intensive vs Moderate Antihypertensive Treatment on Stroke Incidence in Diabetic Normotensives,Intensive
14、 Moderate Achieved BP (mmHg) 128/75 137/81 Stroke (%) 1.7 5.4,Schrier et al., Kidney Int 2002; 61:1086,CHD Prevention Trials with Statins in Diabetic Subjects Subgroup Analyses,Primary Prevention AFCAPS/TexCAPS Secondary Prevention CARE 4S LIPID 4S-Extended,CHD Risk Reduction (overall),Drug,No.,Lova
15、statin Pravastatin Simvastatin Pravastatin Simvastatin,43% 25% (p=0.05) 55% (p=0.002) 19% 42% (p=0.001),37% 23% 32% 25% 32%,239 586 202 782 483,CHD Risk Reduction (diabetes),Study,Adapted from Downs JR et al. JAMA 1998;279:1615-1622; Goldberg RB et al. Circulation 1998;98:2513-2519; Pyrl K et al. Di
16、abetes 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;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, Betteri
17、dge DJ, Durrington PN, et al. Lancet. 2004;364:685-696.,37,Trials with Fibrates in Patients with Diabetes,FIELD Study Fenofibrate Intervention and Event Lowering in Diabetes,Mazzone T. Am J Cardiol 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 Study
18、Multifactorial 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,脂肪摄入30% 饱和脂肪酸摄入10% 运动 3035次/w ACEI or ARB 多种维生素 Aspirin,Pharmacology Intervention,降糖 metformin gl
19、iclazide metformin + gliclazide 降压 thiazide ACEI or ARB + CCB -blocker 降脂 statins,Steno-2: Treatment Goals,Variable Conventional Intensive Therapy Therapy SBP (mmHg) 140 130 DBP (mmHg) 85 80 Hba1c (%) 6.5 6.5 TC (mg/dl) 190 175 TG (mg/dl) 150 150,Steno-2 Change in Clinical Variables at the End of th
20、e Study,Variable Conventional Intensive p Therapy Therapy SBP (mmHg) -33 -142 0.001 DBP (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) -136 -475 0.001 TG (mg/dl) 943 -4114 0.015,Steno-2 S
21、tudy: 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。,