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1、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 2000More than 60%of US adults are overweightOnly 43%of obese persons advised to lose weight during checkupsBMI and w
2、eight gain major risk factors for diabetes,Prevalence(%),DiabetesMean 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 prevalence of diabetes*,246 million people with diabetes worldw
3、ide=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,GermanyBy 2025,the largest increases in diabetes prevalence will occur in low-and middle-income countriesEach year an additional 7 million people wor
4、ldwide 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 deaths worldwide are attributable to diabetesDiabetes is associated with compl
5、ications such as:Diabetic neuropathy Renal failureBlindnessMacrovascular diseaseMacrovascular 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 Heart J 1999;138:5330,欧洲心脏调查结果,n=2107,n=2854,The Euro Heart Survey on diabetes and t
6、he 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
7、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,smoking,BMI,visceral obesity,physical activity,BP and dyslipidemia.,Adapted from:Selvin,E.et col
8、l.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-diabetics with a prior myocardial infarction carry the same cardiovascular risk:A population study of 3.3 millio
9、n peopleCirculation 117:1945-54,2008,All 3.3 mio Danes older than 30 years were followed from 1997 to 2002 by nation wide registersMedication treated diabetes patients and nondiabetics with and without a prior myocardial infarction were comparedAt baseline 71,801 Danes had medication treated diabete
10、s and 79,575 had a prior myocardial infarctionRelative risk for CVD mortality was 2.42 in men with diabetes mellitus without a prior myocardial infarctionand2.44 in nondiabetic men with a prior myocardial infarction(P=0.60),Hazard Ratio,Diabetes,Glucose,and CV Disease,DM is an established risk facto
11、r for CVDIn 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&Nonfatal Stroke,Hazard Ratio,14%rise per 1%rise in A1C,P.0001,10,1,0.5,Fatal&Nonfatal MI,10,43%rise per 1%rise in A1C,P.0001,10,1,0.5,Amputation/Death from PVD,
12、6,5,7,8,9,16%rise per 1%rise in A1C,P.021,Heart Failure,6,5,7,8,9,10,UK Prospective Diabetes Study,Blood glucose and vascular risk in diabetes-UKPDS,高血糖和心血管风险,越来越多的2型糖尿病患者出现心血管并发症UKPDS 表明高血糖和心血管疾病之间存在流行病学上的关联但是严格的血糖控制能否降低该风险?ACCORD,ADVANCE&VADT 等大型研究就是针对上述问题而设计,ACCORD:2型糖尿病强化降糖的效应研究,多中心研究(77 研究中心)美国
13、/加拿大10,251 例患者(平均年龄 62.2 岁)强化治疗组(目标A1c 6.0%)v 标准治疗组1/3有心血管病史或2个以上心血管危险因素一级终点:非致死性心梗或卒中；心血管死亡,ACCORD:结果,Results of ACCORD,糖尿病心血管风险控制行动(ACCORD),关于执行过程的分析HbA1c降低过快(4 个月下降1.4%)频发严重低血糖(16.2%)TZD(92%)&胰岛素(77%)用量过多平均体重增加 3.5 Kg(4人中有1人增加10 Kg)过于严格的血糖控制目标(HbA1c6.0%),VADT:退伍军人2型糖尿病血糖控制 和血管并发症的研究,美国多中心研究1791 退
14、伍军人(平均年龄 60.4 yrs);97%为男性强化治疗组(A1c 下降1.5%)v 标准治疗组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
15、 Anual Meeting in SanFrancisco No positive trial effect of Intensive glucose lowering on macrovascular complications in type 2 diabetes,at least in the types of patients studied,ACCORDADVANCEVADT,比较:ACCORD,ADVANCE&VADT 研究,Hazard Ratios for the Primary Outcome and Death from Any Cause in Prespecified
16、 Subgroups,Hazard Ratios for the Primary Outcome and Death from Any Cause in Prespecified Subgroups,N Engl J Med,2003;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(1997-2007),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
17、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”效应需要尽早及严格血糖控制可能获得长期的心血管获益,Steno-2 Post Trial aim,1To examine whether an intensified m
18、ultifactorial intervention similar to current guidelines has an impact on mortality in patients with type 2 diabetes and microalbuminuria,2To examine whether risk reductions already achieved for both macro-and microvascular disease with intensified multifactorial intervention were sustained in a cli
19、nical setting outside the structured framework of a clinical trial,STENO-2Percentage of Patients Who Reached the Intensive-Treatment Goals at a Mean of 7.8 Years,Gde P et al.NEJM.2003;348:383393.,STENO-2Composite End Point of Death from CV Causes,Nonfatal MI,CABG,PCI,Nonfatal Stroke,Amputation,or Su
20、rgery 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 riskConventionalIntensive,Steno-2 Post Trial:Mortality,8080,8078,7775,6972,6365,5162,4357,HR=0.54(0.32-0.89),P=0.015,3039,Years of follow-up,Percentage of patients dying(%),G
21、aede 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 associated with long-term reduction in risk of macrovascular diasease.Until more evidence becomes available,the general
22、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 hy
23、poglycemia or other adverse effects of treatment.,Implications of these findings for clinical care,Conversely,less stringent A1C goals 7%may be appropriate for patients with a history of severe hypoglycemia,limited life expectancy,advanced microvascular or macrovascular complications,or extensive co
24、morbid conditions or those with long-standing diabetes in whom the general goal is difficult to attain.,Implications of these findings for clinical care,For primary and secondary CVD risk reduction in patients with diabetes,providers should continue to follow the evidence-based recommendations for blood pressure treatment,lipid-lowering with statins,aspirin prophylaxis,smoking cessation,and healthy lifestyle behaviors.,糖尿病:Getting the balance right 生活质量和长寿,谢 谢！,
