糖尿病脂代谢紊乱的治疗与临床指南 ppt课件

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,Clinical Trials and Guidelines for Lipid Management in the Diabetic Patient,Steven Haffner, MD,Clinical Trials and Guidelines,UKPDS Design,Aim,To determine whether intensified blood glucose control, with either sulphonylurea or insulin, reduces the risk of macrovascular or microvascular complications in type 2 diabetes,Patients,3867 newly diagnosed type 2 diabetic patients who were asymptomatic after 3 months of diet; fasting glucose 6.1-15 mmol/L (110-270 mg/dl); treat for 10 years,Adapted from UK Prospective Diabetes Study (UKPDS) Group.,Lancet,1998;352:837-853; Turner R et al.,Ann Intern Med,1996;124:136-145.,UKPDS DesignAimAdapted from UK,UKPDS Group.,Lancet,1998;352:837-853.,UKPDS 10-Year Follow-up Results:,Glycemic Control, Weight, and Plasma Insulin,Years from Randomization,0,1,2,3,4,5,6,7,8,9,10,11,12,0,1,2,3,4,5,6,7,8,9,10,11,12,Years from Randomization,Conventional,Conventional,Intensive,Intensive,Conventional,Intensive,Intensive,Conventional,Fasting plasma glucose,Median (mmol/L),Hemoglobin A,1c,Weight,Plasma insulin,11,10,9,8,7,6,0,Median (%),9,8,7,6,0,7.5,5,2.5,0,-2.5,Baseline = 75 kg,Mean Change (kg),40,30,20,10,0,-10,-20,Median Change (pmol/L),Baseline = 89 pmol/L,UKPDS Group. Lancet 1998;352:8,UKPDS: Proportion of Patients Taking Different Therapies in the Conventional-Therapy Group,Courtesy of Dr. Amanda Adler,% of patients,100,80,60,40,20,Diet alone,1,3,5,7,9,11,Years from randomization,Additionalpharmacologictherapy,UKPDS: Proportion of Patients,UKPDS: Causes of Death by Glucose Treatment Group,Rate/1000patient-years,MIStrokeSudden deathPVD,All macrovascular,Renal disease,CancerOther specifiedUnknown,Total,UKPDS Group.,Lancet,1998;352:837-853.,%,Rate/1000patient-years,%,7.61.60.90.1,10.2,0.3,4.42.40.5,17.8,Cause,43951,58,2,25133,100,8.01.31.60.3,11.2,0.2,4.42.70.2,18.7,43782,60,1,24141,100,Conventional,Intensive,UKPDS: Causes of Death by Gluc,UKPDS: Endpoints by Glucose Treatment Group,Rate/1000Patient-Years,Any diabetes-related*,MI,Stroke,PVD*,Microvascular,UKPDS Group.,Lancet,1998;352:837-853.,Rate/1000Patient-Years,P,Cause,40.9,14.7,5.6,1.1,8.6,*,Combined microvascular and macrovascular events*Amputation or death from PVD,% RiskReduction,46.0,17.4,5.0,1.6,11.4,0.029,0.052,0.52,0.15,0.0099,12,16,25,Conventional,Intensive,UKPDS: Endpoints by Glucose T,UKPDS: Impact of Glucose-Lowering Agents on MI and Stroke,Sulphonylurea or exogenous insulin (n=2729),MI 16% reduction (P = 0.052),Stroke 11% increase (P = 0.52),Metformin in overweight subjects (n = 342),MI 39% reduction (P = 0.01),Stroke 41% reduction (P = 0.13),Adapted from UK Prospective Diabetes Study (UKPDS) Group.,Lancet,1998;352:837-853; UK Prospective Diabetes Study (UKPDS) Group.,Lancet,1998;352:854-865.,UKPDS: Impact of Glucose-Lower,UKPDS Results: Intensive Blood Pressure Control,Any diabetes-related endpoint,Deaths related to diabetes,Myocardial infarction,Stroke,Microvascular disease,Intensive BloodPressure Control,24,32,21,44,37,0.0046,0.019,NS,0.013,0.092,Adapted from UK Prospective Diabetes Study Group.,BMJ,1998;317:703-713.,Reduction(%),P Value,UKPDS Results: Intensive Bloo,Comparison of Captopril vs. Atenolol in UKPDS,Primary,Any diabetes-related endpoint,Death related to diabetes,All-cause mortality,Secondary,Myocardial infarction,Stroke,Peripheral vascular disease,Microvascular disease,Clinical Endpoint,Adapted from UK Prospective Diabetes Study Group.,BMJ,1998;317:713-720.,RR forCaptopril,P Value,1.10 (0.861.41),1.27 (0.821.97),1.14 (0.811.61),1.20 (0.821.76),1.12 (0.592.12),1.48 (0.356.19),1.29 (0.802.10),0.43,0.28,0.44,0.35,0.74,0.59,0.30,Comparison of Captopril vs. At,Comparison of Glucose Lowering and Blood Pressure Lowering in UKPDS,Any diabetes-related endpoint,Myocardial infarction,Stroke,Microvascular disease,12,16,11,25,Reduction %,= Increase in risk,Adapted from UK Prospective Diabetes Study (UKPDS) Group.,Lancet,1998;352:837-853; UK Prospective Diabetes Study Group.,BMJ,1998;317:703-713.,PValue,Reduction %,PValue,Intensive BloodGlucose Control (n=2729),Intensive BloodPressure Control (n=758),0.029,0.052,NS,0.0099,24,21,44,37,0.0046,NS,0.013,0.092,Comparison of Glucose Lowering,Treatment Strategies for Diabetic Dyslipidemia,Primary Strategy,- Lower LDL cholesterol,Secondary Strategy,- Raise HDL cholesterol,- Lower triglycerides,Other Approaches,- Non-HDL cholesterol,- ApoB,- Remnants,Adapted from American Diabetes Association.,Diabetes Care.,2000;23(suppl 1):S57-S60; Chait A, Brunzell JD.,Diabetes Mellitus.,A Fundamental and Clinical Text. Philadelphia: Lippincott Raven, 1996;772-779; European Diabetes Policy Group 1999.,Diabet Med.,1999;16:716-730.,Treatment Strategies for Diabe,CHD Prevention Trials with Statins in Diabetic Subjects:,Subgroup Analyses,Primary Prevention,AFCAPS/TexCAPS,Secondary Prevention,CARE,4S,LIPID,BaselineLDL-C,mg/dl(mmol/L),*Values for overall group,Adapted 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; Haffner SM et al.,Arch Intern Med,1999;159:2661-2667; The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group.,N Engl J Med,1998;339:1349-1357.,Drug,No.,LDL-CLowering,Lovastatin,Pravastatin,Simvastatin,Pravastatin,25%,28%,36%,25%*,150 (3.9),136 (3.6),186 (4.8),150* (3.9),239,586,202,782,Study,CHD Prevention Trials with Sta,CHD Prevention Trials with Statins in Diabetic Subjects:,Subgroup Analyses,(contd),Primary Prevention,AFCAPS/TexCAPS,Secondary Prevention,CARE,4S,LIPID,4S-Extended,CHD RiskReduction(overall),Drug,No.,Lovastatin,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 RiskReduction(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.,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.,CHD Prevention Trials with Sta,Adapted from Pyrl et al.,Diabetes,Care,1997;20:614-620.,Diabetic vs. Nondiabetic Patients in 4S,0,0.2,0.4,0.8,1.4,Relative Risk with 95% Confidence Intervals,Total mortality,0.6,1.0,1.2,Reduced,Increased,CHD mortality,Simvastatin Better,Placebo Better,Major CHD event,Cerebrovascular event,Any atherosclerotic event,P=0.001P=0.087,P0.0001P=0.242,P0.0001P=0.002,P=0.097P=0.071,P,7 mmol/L (126 mg/dl),0.0,0.2,0.4,0.8,1.4,Relative Risk,CHD mortality (P=0.26),Total mortality (P=0.34),Revascularizations (P=0.005),Major coronary events (P=0.001),0.6,1.0,1.2,0.72,0.79,0.52,0.58,Adapted from Haffner SM et al.,Adapted from Haffner SM et al.,Arch,Intern,Med,1999;159:2661-2667,4S: Extended Diabetic Subgroup Analysis:,Impaired Fasting Glucose (n=678; 343 on Simvastatin) Fasting Glucose 6.0-6.9 mmol/L (110-125 mg/dl),0.0,0.2,0.4,0.8,1.4,Relative Risk,CHD mortality (P=0.007),Total mortality (P=0.02),Revascularizations (P=0.01),Major coronary events (P=0.003),0.6,1.0,1.2,0.45,0.57,0.57,0.62,Adapted from Haffner SM et al.,Simvastatin,Normal fastingglucose,Bed Days (per 100 Pts),4S:,Effect of Statin Therapy on Hospital Stay,Adapted from Herman WH et al.,Diabetes,Care,1999;22:1771-1778.,55%(p0.001),Placebo,Simvastatin,Impaired fastingglucose,Placebo,Simvastatin,Placebo,Diabetesmellitus,38%(p=0.005),28%(p0.001),SimvastatinNormal fastinggluc,CARE: Major Coronary Events in Diabetic Subgroups,Adapted from Goldberg RB et al.,Circulation,1998;98:2513-2519.,45,35,30,25,20,15,10,5,0,Percent with Event,No Diabetes by History,Diabetes by History,Follow-up Time (years),Percent with Event,45,35,30,25,20,15,10,5,0,Follow-up Time (years),0,1,2,3,4,6,5,0,1,2,3,4,6,5,Placebo,Pravastatin,Pravastatin,Placebo,Relative risk = 0.75P=0.05,Relative risk = 0.77P0.001,CARE: Major Coronary Events i,% Risk Reduction,AFCAPS/TexCAPS: Subgroup Analysis,Downs JR et al.,JAMA,1998;279:1615-1622.,Men,Women,Older,Smokers,HTN,Diabetes,-37,-46,-31,-58,-38,-42,Lovastatin Reduced the Risk of Acute MCE,% Risk ReductionAFCAPS/TexCAPS,CARE: Major Coronary Events in Diabetic Subgroups,Adapted from Goldberg RB et al.,Circulation,1998;98:2513-2519.,45,40,35,30,25,20,15,10,5,0,Percent with Event,No Diabetes by History,Diabetes by History,Follow-up Time (years),Percent with Event,Follow-up Time (years),0,1,2,3,4,6,5,0,1,2,3,4,6,5,Placebo,Pravastatin,Pravastatin,Placebo,Relative risk = 0.75P=0.05,Relative risk = 0.77P0.001,45,40,35,30,25,20,15,10,5,0,CARE: Major Coronary Events i,Per-Patient % of Grafts,POST-CABG: Effect of Aggressive Lipid Lowering on Progression in a Diabetic Subgroup,Hoogwerf BJ et al.,Diabetes,. 1999;48:1289-1294.,AggressiveRx,ModerateRx,AggressiveRx,ModerateRx,Diabetes,(n=116),No Diabetes,(n=1235),99% CI(0.20-1.19),99% CI(0.46-0.79),51%,40%,Per-Patient % of GraftsPOST-CA,CHD Prevention Trials with Fibrates in Diabetic Subjects:,Subgroup Analyses,Primary Prevention,HelsinkiHeart Study,Secondary Prevention,VA-HIT,BaselineLDL-C,mg/dl(mmol/L),No.,LDL-CLowering,Adapted from Koskinen P et al.,Diabetes Care,1992;15:820-825; Rubins HB et al.,N Engl J Med,1999;341:410-418.,DrugDose,Study,CHDReduction,Gemfibrozil(1200 mg/d),Gemfibrozil(1200 mg/d),135,627,203(5.2),112(2.9),68%NS,24%,p=0.05,6%,CHD Prevention Trials with Fib,Primary CHD* Prevention in Type 2 Diabetic Patients:,The Helsinki Heart Study,5-Year Incidence of CHD (%),Type 2(n=135),*,Myocardial infarction or cardiac death,Adapted from Koskinen P et al.,Diabetes Care,1992;15:820-825.,Others(n=3946),Type 2 on Placebo(n=76),Type 2 onGemfibrozil(n=59),P65, n 10,000) Diabetics (n 6,000) Stroke (n 3,000) Hypertension (n 8,000) Noncoronary vascular disease (n 7,000) Low to average blood cholesterol (n 8,000),FPI 1996, fully enrolled, results 2001,Medical Research Council. August 1994,Heart Protection StudyPrimary,Endpoint Studies: Treating to New Targets (TNT):,Study Design,Site SelectionNovember 1997,InvestigatorMeetingMarch 1998,RecruitmentCompleteJune 1999,Study EndDec 2004,Atorvastatin10 mg,LDL75 mg/dL,LDL100 mg/dL,5 Years,Atorvastatin80 mg,10,000 CAD Patients,Endpoint Studies: Treating to,Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine with Simvastatin and Folic Acid/Vitamin B,12,(SEARCH):,Study Design,Primary objective:,To determine whether the greater cholesterol reductions achieved with simvastatin 80 mg produce greater CHD reductions in post-MI patients than achieved with simvastatin 20 mg,Secondary prevention,2x2 factorial design:simvastatin 20 or 80 mg; 2 mg folic acid/1 mg Vitamin B,12,N = 12,000,FPI 12/97, results 2003,Study of the Effectiveness of,Cerivastatin Arm,Fenofibrate Arm,CerivastatinFenofibrate(n=1,250),PlaceboFenofibrate(n=1,250),CerivastatinPlacebo(n=1,250),PlaceboPlacebo(n=1,250),2,500activefenofibrate,2,500placebofenofibrate,n=2,500 activecerivastatin,n=2,500 placebocerivastatin,5,000 ptsin total,Lipids in Diabetes Study (LDS):,Two-by-Two Factorial Randomization,Cerivastatin ArmFenofibrate Ar,Conclusions,CHD risk is extremely high in diabetic subjects,Benefits of risk-factor modification in intervention trials also apply to subgroups with diabetes,Results of strict glycemic control on macrovascular disease are inconclusive,ConclusionsCHD risk is extreme,糖尿病脂代谢紊乱的治疗与临床指南 ppt课件,