2型糖尿病患者严格血糖控制和心血管事件的预防

1、2型糖尿病患者严格血糖控制和心血管事件的预防,中山大学附属第一医院内分泌科 肖 海 鹏,Challenge,To have patients believe in your guidance for the management of their diabetes mellitus,National Geographics (2004) August,Prevalence of obesity increased 61% between 1991 and 2000 More than 60% of US adults are overweight Only 43% of obese perso

2、ns advised to lose weight during checkups BMI and weight gain major risk factors for diabetes,Prevalence (,Diabetes Mean body weight,kg,Year,Mokdad et al. Diabetes Care. 2000;23:1278. Mokdad et al. JAMA. 1999;282:1519. Mokdad et al. JAMA. 2001;286:1195,Prevalence of Diabetes and Obesity,Global preva

3、lence of diabetes,246 million people with diabetes worldwide = roughly 6% of the adult population In 2007, the five countries with the largest numbers of people with diabetes are: India, China, United States, Russia, Germany By 2025, the largest increases in diabetes prevalence will occur in low- an

4、d middle-income countries Each year an additional 7 million people worldwide develop diabetes,Diabetes Atlas, 3rd edition, International Diabetes Federation, 2006,中国的2型糖尿病管理面临严峻的挑战,中国的糖尿病患者可能居世界之最” “经济的迅速发展，带来了传统生活方式的根本性变革，导致了中国2型糖尿病患者的剧增。” 潘长玉 301医院,Diabetes complications,Each year 3.8 million deat

5、hs worldwide are attributable to diabetes Diabetes is associated with complications such as: Diabetic neuropathy Renal failure Blindness Macrovascular disease Macrovascular complications are a major cause of death in people with diabetes,心血管疾病在糖尿病者中的比率,新诊断的2型糖尿病患者25% 总糖尿病人群50% 占糖尿病死亡原因 65-75,Am Hear

6、t J 1999;138:5330,欧洲心脏调查结果,n=2107,n=2854,The Euro Heart Survey on diabetes and the heart，European Heart Journal (2004) 25, 18801890,43,509 例高危人群中9,125例合并心血管疾病 OGTT 结果,任一心血管事件, n=9,125,NGT I-IFG IGT DM,相对比例 (,Presentation of Novartis Satellite symposium during ESC 2004,Munich,Germany,NAVIGATOR,GAMI:急

7、性心梗患者中的糖代谢异常,心肌梗死患者,Bartnik M, et al. J Intern Med. 2004 Oct;256(4):288-97,中国心脏调查结果-汇总（n=3513,中华内分泌代谢杂志 2006, 22:7,Risk of cardiovascular disease (CVD) in relation to HbA1c The ARIC Study,Relative risk of CVD,n = 1626 (p 0.001,5.2,5.2 5.7,5.7 6.5,6.5 8.2,8.2,HbA1c,Ajusted for age, gender, race, smok

8、ing, BMI, visceral obesity, physical activity, BP and dyslipidemia,Adapted from: Selvin, E. et coll. Arch. Int. Med. 165: 1910-1916, 2005,GAMI :新诊断高血糖是心肌梗死后“无心血管事件存活”的预测因素,Bartnik M, et al. Eur Heart J. 2004;25(22):1990-7,中位数随访时间:34月,Diabetes patients requiring glucose-lowering therapy and non-diabe

9、tics with a prior myocardial infarction carry the same cardiovascular risk: A population study of 3.3 million people Circulation 117:1945-54, 2008,All 3.3 mio Danes older than 30 years were followed from 1997 to 2002 by nation wide registers Medication treated diabetes patients and nondiabetics with

10、 and without a prior myocardial infarction were compared At baseline 71, 801 Danes had medication treated diabetes and 79, 575 had a prior myocardial infarction Relative risk for CVD mortality was 2.42 in men with diabetes mellitus without a prior myocardial infarction and 2.44 in nondiabetic men wi

11、th a prior myocardial infarction (P=0.60,Hazard Ratio,Diabetes, Glucose, and CV Disease,DM is an established risk factor for CVD In DM, higher glucose levels/A1c predict higher CV risk,Stratton IM, et al. BMJ 2000; 321:405412,12% rise per 1% rise in A1C,P .035,Fatal 97%为男性 强化治疗组(A1c 下降1.5%) v 标准治疗组

12、40% 有既往心血管病史 一级终点: 主要心血管事件的发生时间 (复合终点,VADT: 结果和分析,平均随访 5.6 年 A1c 6.9% A1c 在6个月内降低2% 心血管终点和死亡率上没有显著性差异 体重增加 9 Kg 严重低血糖发生率 21.2,ADVANCE 协作组研究 2型糖尿病强化降压/降糖和血管事件结果,2型糖尿病患者严格血糖控制和血管结局,ADVANCE: 析因设计,ADVANCE: 血糖结果,ADVANCE: 终点结果,微血管和大血管复合终点结果,主要大血管事件,全因死亡,微血管事件,ADA 2008 Anual Meeting in SanFrancisco No posi

13、tive trial effect of Intensive glucose lowering on macrovascular complications in type 2 diabetes, at least in the types of patients studied,ACCORD ADVANCE VADT,比较: ACCORD, ADVANCE 348:2294-303,DCCTEDIC：早期代谢控制的益处颈动脉内膜厚度,DCCT/EDIC Study累积的心血管事件数,欧洲糖尿病协会减少2型糖尿病心血管风险英国前瞻性糖尿病研究20年干预 研究结束后10年随访结果 (1997-2

14、007,Mean (95%CI,UKPDS 结束10年后随访结果：HbA1c的变化,磺脲类/胰岛素 vs. 常规治疗,微血管疾病风险比,心梗风险比,全因死亡风险比,早期血糖控制所带来的延续效应(Legacy Effect )研究结束后随访8.5年结果,1 Rury R. Holman et al, N Engl J Med. 2008 ;359(15):1618-20,RRR = Relative Risk Reduction, P = Log Rank,强化治疗 (磺脲类/胰岛素) vs. 常规治疗,2型糖尿病强化组长期随访结果UKPDS: 延迟效应,实际意义: 提示“血糖记忆”效应 需要尽

15、早及严格血糖控制 可能获得长期的心血管获益,47,Steno-2 Post Trial aim,1 To examine whether an intensified multifactorial intervention similar to current guidelines has an impact on mortality in patients with type 2 diabetes and microalbuminuria,2 To examine whether risk reductions already achieved for both macro- and mic

16、rovascular disease with intensified multifactorial intervention were sustained in a clinical setting outside the structured framework of a clinical trial,STENO-2 Percentage of Patients Who Reached the Intensive-Treatment Goals at a Mean of 7.8 Years,Gde P et al. NEJM. 2003;348: 383393,STENO-2 Compos

17、ite End Point of Death from CV Causes, Nonfatal MI, CABG, PCI, Nonfatal Stroke, Amputation, or Surgery for Peripheral Atherosclerotic Artery Disease,Gde P et al. NEJM. 2003;348: 383393,Steno-2 研究: 2型糖尿病多因素干预对死亡率的影响,Numbers at risk Conventional Intensive,Steno-2 Post Trial: Mortality,80 80,80 78,77 7

18、5,69 72,63 65,51 62,43 57,HR=0.54 (0.32-0.89), P=0.015,30 39,Years of follow-up,Percentage of patients dying (,Gaede P et al. NEJM 358: 580-591, 2008,Implications of these findings for clinical care,Treatment to A1C targets below or around 7% in the years soon after the diagnosis of diabetes is asso

19、ciated with long-term reduction in risk of macrovascular diasease. Until more evidence becomes available, the general goal of 7% appears reasonable. (ADA, B-level,Implications of these findings for clinical care,For selected individuals, including those with short duration of DM, long life expectancy , and no significant cardiovascular disease. HbA1C less than 7% is reasonable if this can be achieved without significant hypoglycemia or other adverse effects of treatment,Implications of these findings for clinical care,Conversely, les