1、2型糖尿病患者嚴(yán)格血糖控制和心血管事件的預(yù)防,中山大學(xué)附屬第一醫(yī)院內(nèi)分泌科 肖 海 鵬,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,中國(guó)的2型糖尿病管理面臨嚴(yán)峻的挑戰(zhàn),中國(guó)的糖尿病患者可能居世界之最” “經(jīng)濟(jì)的迅速發(fā)展，帶來了傳統(tǒng)生活方式的根本性變革，導(dǎo)致了中國(guó)2型糖尿病患者的劇增。” 潘長(zhǎng)玉 301醫(yī)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,新診斷的2型糖尿病患者25% 總糖尿病人群50% 占糖尿病死亡原因 65-75,Am Hear

6、t J 1999;138:5330,歐洲心臟調(diào)查結(jié)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 結(jié)果,任一心血管事件, n=9,125,NGT I-IFG IGT DM,相對(duì)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謝異常,心肌梗死患者,Bartnik M, et al. J Intern Med. 2004 Oct;256(4):288-97,中國(guó)心臟調(diào)查結(jié)果-匯總（n=3513,中華內(nèi)分泌代謝雜志 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 :新診斷高血糖是心肌梗死后“無心血管事件存活”的預(yù)測(cè)因素,Bartnik M, et al. Eur Heart J. 2004;25(22):1990-7,中位數(shù)隨訪時(shí)間: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%為男性 強(qiáng)化治療組(A1c 下降1.5%) v 標(biāo)準(zhǔn)治療組

12、40% 有既往心血管病史 一級(jí)終點(diǎn): 主要心血管事件的發(fā)生時(shí)間 (復(fù)合終點(diǎn),VADT: 結(jié)果和分析,平均隨訪 5.6 年 A1c 6.9% A1c 在6個(gè)月內(nèi)降低2% 心血管終點(diǎn)和死亡率上沒有顯著性差異 體重增加 9 Kg 嚴(yán)重低血糖發(fā)生率 21.2,ADVANCE 協(xié)作組研究 2型糖尿病強(qiáng)化降壓/降糖和血管事件結(jié)果,2型糖尿病患者嚴(yán)格血糖控制和血管結(jié)局,ADVANCE: 析因設(shè)計(jì),ADVANCE: 血糖結(jié)果,ADVANCE: 終點(diǎn)結(jié)果,微血管和大血管復(fù)合終點(diǎn)結(jié)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,比較: ACCORD, ADVANCE 348:2294-303,DCCTEDIC：早期代謝控制的益處頸動(dòng)脈內(nèi)膜厚度,DCCT/EDIC Study累積的心血管事件數(shù),歐洲糖尿病協(xié)會(huì)減少2型糖尿病心血管風(fēng)險(xiǎn)英國(guó)前瞻性糖尿病研究20年干預(yù) 研究結(jié)束后10年隨訪結(jié)果 (1997-2

14、007,Mean (95%CI,UKPDS 結(jié)束10年后隨訪結(jié)果：HbA1c的變化,磺脲類/胰島素 vs. 常規(guī)治療,微血管疾病風(fēng)險(xiǎn)比,心梗風(fēng)險(xiǎn)比,全因死亡風(fēng)險(xiǎn)比,早期血糖控制所帶來的延續(xù)效應(yīng)(Legacy Effect )研究結(jié)束后隨訪8.5年結(jié)果,1 Rury R. Holman et al, N Engl J Med. 2008 ;359(15):1618-20,RRR = Relative Risk Reduction, P = Log Rank,強(qiáng)化治療 (磺脲類/胰島素) vs. 常規(guī)治療,2型糖尿病強(qiáng)化組長(zhǎng)期隨訪結(jié)果UKPDS: 延遲效應(yīng),實(shí)際意義: 提示“血糖記憶”效應(yīng) 需要盡

15、早及嚴(yán)格血糖控制 可能獲得長(zhǎng)期的心血管獲益,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型糖尿病多因素干預(yù)對(duì)死亡率的影響,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