控制糖尿病患者心血管危险控制糖尿病患者心血管危险的干预治疗策略的干预治疗策略糖尿病与心血管危险糖尿病与心血管危险影响心血管危险的因素影响心血管危险的因素综合控制的理论与实践综合控制的理论与实践Countries With Highest Numbers of EstimatedCases of Diabetes for 2000 and 2030RankingCountryPeople with diabetes(millions)CountryPeople with diabetes(millions)200020301India31.7India79.42China20.8China42.33U.S.17.7U.S.30.34Indonesia8.4Indonesia21.35Japan6.8Pakistan13.96Pakistan5.2Brazil11.37Russian Federation4.6Bangladesh11.18Brazil4.6Japan8.99Italy4.3Pinecones7.810Bangladesh3.2Egypt16.7Total: 177 million366 MILLION BY 2030Type 2 diabetes and CHD7-Year Incidence of Fatal/Nonfatal MI (East West Study) Incidence During Follow-up (%)(n=69)Nondiabetics with prior MINondiabetics with no prior MIDiabetics with prior MIDiabetics with no prior MI18.8Haffner SM et al. N Engl J Med 1998;339:229-234.(n=1304)(n=169)(n=890)3.00.57.83.23.545.020.2Events per100 person-yr:P0.001p0.001Type 2 diabetes and Stroke7-Year Incidence of 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 MI7.2Haffner SM et al. N Engl J Med 1998;339:229-234.(n=1304) (n=169)(n=890)1.20.33.41.61.919.510.3Events per100 person-yr:P=0.01p0.001Prevalence of CHD by the Metabolic Syndrome and Diabetes in the NHANES Population Age 50+Alexander C et al. Diabetes 2003;52:1210-121425%20%15%10%5%0%No MS/No DM8.7%13.9%7.5%19.2%MS/No DMDM/No MSDM/MS% of population = 54.2%28.7%2.3%14.8%CHD Prevalence1.00.90.80.70.60.00246810Follow-up, years# at risk174214099062828935No metabolic syndromeMetabolic syndromelog-rank = 45.4 p0.001Event-free survivalSchillaci G. JACC. 2004; 43:1817-1822代谢综合征与心血管危险代谢综合征与心血管危险Ml and Microvascular End Points: Incidence byMean Systolic BP and HbA1c ConcentrationMlMicrovascular and pointsMlMicrovascular and points50403020100806040200Adjusted incidence per 1000 person-yr (%)110 120130 140 150160170567891011Updated mean systolic BP (mmHg)Updated mean HbA1c concentration (%)Adjusted incidence per 1000 person-yr (%)Adler Al et al. BMJ 2000;321:412-419Stration IM et al. BMJ 2000;321:405-412MetS和和DM患者血脂异常特征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MaleGender-adjustedFemaleReduced risk with small, dense LDL0.1Relative risk for myocardial infarction110Increased risk with small, dense LDLSmall, dense LDL increases cardiovascular riskUKPDS Stepwise Selection of Risk Factors* in Patients with Type 2 Diabetes VariableVariableLDL-CHDL-CHemoglobin A1cSystolic Blood PressureSmokingP ValueP Value0.0001 0.0001 0.0022 0.00650.056Coronary Artery Disease (n=280)Position in ModelPosition in ModelFirstSecondThirdFourthFifth*Adjusted for age and sex.Turner RC et al. BMJ 1998;316:823-828.Mangaging overweight in type 2 diabeticsEffective weight management is the first step in treating type 2 diabetesWeight loss (kg) in first 12 monthsWeight loss (kg) in first 12 monthsLean MEJ et al., Diabet Med, 1990;7:228-233Life expectancy (years)Life expectancy (years)95% confidence interval95% confidence interval181816161414121210108 80 00 04 48 812121616Weight loss is difficult to maintain by dietand exercise alone in type 2 diabetesUKPDS 34. Lancet 1998;352:354InsulinChlorpropamideGllbenclamideDiet aloneMetforminWeight change (kg)76543210-10246810Years from randomisationGood glycemic control is not enoughUKPDSGOOD GLYCEMIC CONTROLMICROVASCULAR COMPLICATIONSSignificant reductionsMACROVASCULAR COMPLICATIONSNo significant effectPROACTIVE StudySept. 2005, 欧洲糖尿病会议欧洲糖尿病会议 Pioglitazone vs PlaceboACCORD StudyAction to Control Cardiovascular risk in DiabetesPrisant LM. J Clin Pharmacol 2004; 44(4):423-430HbA1c: 6.0% vs 7.0-7.9% 糖尿病患者降压治疗临床试验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, and 80 mm Hg. 302520151050 80 85 90 90 85 80P=0.50 for trendP=0.005 for trendAll hypertensive patients(n=18790)Hypertensive with diabetes(n=1501)Target blood pressure groupsMajor cardiovascular events/1000 patients-yearsHOT Study: Results in Patients with DMEffect of Intensive vs Moderate Antihypertensive Treatmenton Stroke Incidence in Diabetic NormotensivesIntensiveModerateAchieved BP (mmHg)128/75137/81Stroke (%)1.75.4P = 0.03Schrier et al., Kidney Int 2002; 61:1086CHD Prevention Trials with Statins in Diabetic Subjects Subgroup Analyses Primary PreventionAFCAPS/TexCAPSSecondary PreventionCARE4SLIPID4S-ExtendedCHD RiskCHD RiskReductionReduction(overall)(overall)DrugDrugNo.No.LovastatinPravastatinSimvastatinPravastatinSimvastatin43%25% (p=0.05)55% (p=0.002)19%42% (p=0.001)37%23%32%25%32%239586202782483CHD RiskCHD RiskReductionReduction(diabetes)(diabetes)StudyStudyAdapted 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;159:2661-2667.CARDS: 主要终点主要终点年年安慰剂组事件数 127立普妥组事件数 83累积危险累积危险 (%)(%)051015012344.75P=0.001Colhoun HM, Betteridge DJ, Durrington PN, et al. Lancet. 2004;364:685-696. 37Trials with Fibrates in Patients with DiabetesStudyEffectp-valueCommentHelsinki Heart Helsinki Heart StudyStudy( (gemfibrozilgemfibrozil) )75% 75% eventseventsnsnsPrimary prevention; Primary prevention; post-hoc subgroup analysispost-hoc subgroup analysisSENDCAPSENDCAP( (bezafibratebezafibrate) )65% 65% eventsevents0.010.01Specifically conducted in Type 2 Specifically conducted in Type 2 diabetes; post-hoc analysis for IHDdiabetes; post-hoc analysis for IHDVA-HITVA-HIT( (gemfibrozilgemfibrozil) )24%24%eventsevents0.050.05Secondary intervention; pre-planned Secondary intervention; pre-planned subgroup analysissubgroup analysisDAISDAIS( (fenofibratefenofibrate) )40-42%40-42%focal focal angioangio changeschanges0.020.02Specifically conducted in Type 2 Specifically conducted in Type 2 diabetes; mixed primary and diabetes; mixed primary and secondary intervention; secondary intervention; angioangio study studyFIELD StudyFenofibrate Intervention and Event Lowering in DiabetesMazzone 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/LSteno-2 StudyMultifactorial Intervention and Cardiovascular Disease in Patients with Type 2 DiabetesGrade P, et al. N ENGL J MED 2003;348:383-393Steno-2: Intensive TherapyNEJM 2000; 342:905-912Basic Intervention脂肪摄入30%饱和脂肪酸摄入10%运动 3035次/wACEI or ARB多种维生素AspirinPharmacology Intervention降糖降糖 metformin gliclazide metformin + gliclazide降压降压 thiazide ACEI or ARB + CCB -blocker降脂降脂 statinsSteno-2: Treatment GoalsVariable Conventional Intensive Therapy TherapySBP (mmHg) 140 130 DBP (mmHg) 85 80 Hba1c (%) 6.5 6.5TC (mg/dl) 190 175 TG (mg/dl) 150 150Steno-2 Change in Clinical Variables at the End of the StudyVariable Conventional Intensive p Therapy TherapySBP (mmHg) -3 3 -14 2 0.001DBP (mmHg) -8 2 -12 2 0.006 Carbohydrates(%) 4.8 0.9 9.3 0.9 0.001 FPG (mg/dl) -18 11 -52 8 0.001 HbA1c (%) 0.2 0.3 -0.5 0.2 0.001 TC (mg/dl) -3 7 -50 4 0.001 LDL-C (mg/dl) -13 6 -47 5 0.001 TG (mg/dl) 9 43 -41 14 0.015 Steno-2 Study: Composite End PointGrade P et al. N Engl J Med 2003;348:383-393Primary composite end point (%)605040302010001224364860728496Months of follow-upHazard ratio = 0.47 (95% Cl 0.24, 0.73) P = 0.008Conventional TherapyIntensive therapy小小 结结 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。