糖尿病脂代谢紊乱的治疗与临床指南医学文档

Clinical Trials and Guidelines for Lipid Management in the Diabetic PatientSteven Haffner, MD,UKPDS Design,AimTo determine whether intensified blood glucose control, with either sulphonylurea or insulin, reduces the risk of macrovascular or microvascular complications in type 2 diabetesPatients3867 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 Group. Lancet 1998;352:837-853.,UKPDS 10-Year Follow-up Results:Glycemic Control, Weight, and Plasma Insulin,Years from Randomization,Years from Randomization,Conventional,Conventional,Intensive,Intensive,Conventional,Intensive,Intensive,Conventional,Fasting plasma glucose,Median (mmol/L),Hemoglobin A1c,Weight,Plasma insulin,11109876,0,Median (%),9876,0,7.552.50-2.5,Baseline = 75 kg,Mean Change (kg),403020100-10-20,Median Change (pmol/L),Baseline = 89 pmol/L,UKPDS: Proportion of Patients Taking Different Therapies in the Conventional-Therapy Group,Courtesy of Dr. Amanda Adler,% of patients,10080604020,Diet alone,1,3,5,7,9,11,Years from randomization,Additionalpharmacologictherapy,UKPDS: Causes of Death by Glucose Treatment Group,Rate/1000patient-years,MIStrokeSudden deathPVDAll macrovascularRenal diseaseCancerOther specifiedUnknownTotal,UKPDS Group. Lancet 1998;352:837-853.,%,Rate/1000patient-years,%,7.61.60.90.110.20.34.42.40.517.8,Cause,4395158225133100,8.01.31.60.311.20.24.42.70.218.7,4378260124141100,Conventional,Intensive,UKPDS: Endpoints by Glucose Treatment Group,Rate/1000Patient-Years,Any diabetes-related*MIStrokePVD*Microvascular,UKPDS Group. Lancet 1998;352:837-853.,Rate/1000Patient-Years,P,Cause,40.914.75.61.18.6,*Combined microvascular and macrovascular events*Amputation or death from PVD,% RiskReduction,46.017.45.01.611.4,0.0290.0520.520.150.0099,121625,Conventional,Intensive,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 Results: Intensive Blood Pressure Control,Any diabetes-related endpointDeaths related to diabetesMyocardial infarctionStrokeMicrovascular disease,Intensive BloodPressure Control,2432214437,0.00460.019 NS0.0130.092,Adapted from UK Prospective Diabetes Study Group. BMJ 1998;317:703-713.,Reduction(%),P Value,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),0.430.280.44 0.350.740.590.30,Comparison of Glucose Lowering and Blood Pressure Lowering in UKPDS,Any diabetes-related endpointMyocardial infarctionStrokeMicrovascular disease,12161125,Reduction %, = Increase in riskAdapted 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),0.0290.052NS0.0099,24214437,0.0046NS0.0130.092,Treatment Strategies for Diabetic Dyslipidemia,Primary Strategy - Lower LDL cholesterolSecondary Strategy - Raise HDL cholesterol - Lower triglyceridesOther 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.,CHD Prevention Trials with Statins in Diabetic Subjects: Subgroup Analyses,Primary PreventionAFCAPS/TexCAPSSecondary PreventionCARE4SLIPID,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,LovastatinPravastatinSimvastatinPravastatin,25%28%36%25%*,150 (3.9)136 (3.6)186 (4.8)150* (3.9),239586202782,Study,CHD Prevention Trials with Statins in Diabetic Subjects: Subgroup Analyses (contd),Primary PreventionAFCAPS/TexCAPSSecondary PreventionCARE4SLIPID4S-Extended,CHD RiskReduction(overall),Drug,No.,LovastatinPravastatinSimvastatinPravastatinSimvastatin,43%25% (p=0.05)55% (p=0.002)19%42% (p=0.001),37%23%32%25%32%,239586202782483,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.,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,P7 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. 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,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),CARE: Major Coronary Events in Diabetic Subgroups,Adapted from Goldberg RB et al. Circulation 1998;98:2513-2519.,4535302520151050,Percent with Event,No Diabetes by History,Diabetes by History,Follow-up Time (years),Percent with Event,4535302520151050,Follow-up Time (years),Placebo,Pravastatin,Pravastatin,Placebo,Relative risk = 0.75P=0.05,Relative risk = 0.77P0.001,% 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,CARE: Major Coronary Events in Diabetic Subgroups,Adapted from Goldberg RB et al. Circulation 1998;98:2513-2519.,454035302520151050,Percent with Event,No Diabetes by History,Diabetes by History,Follow-up Time (years),Percent with Event,Follow-up Time (years),Placebo,Pravastatin,Pravastatin,Placebo,Relative risk = 0.75P=0.05,Relative risk = 0.77P0.001,454035302520151050,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% ,CHD Prevention Trials with Fibrates in Diabetic Subjects: Subgroup Analyses,Primary PreventionHelsinkiHeart StudySecondary PreventionVA-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),135627,203(5.2)112(2.9),68%NS24%p=0.05,6%,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 deathAdapted 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,Endpoint Studies: Treating to New Targets (TNT): Study Design,Site SelectionNovember 1997,InvestigatorMeetingMarch 1998,RecruitmentCompleteJune 1999,Study EndDec 2004,Atorvastatin