1、n To determine whether intensified blood glucose control,with either sulphonylurea or insulin,reduces the risk of macrovascular or microvascular complications in type 2 diabetesn 3867 newly diagnosed type 2 diabetic patients who were asymptomatic after 3 months of diet;fasting glucose 6.1-15 mmol/L(
2、110-270 mg/dl);treat for 10 yearsAdapted 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.Years from Randomization0123456789 10 11 120123456789 10 11 12Years from RandomizationConventionalConvent
3、ionalIntensiveIntensiveConventionalIntensiveIntensiveConventionalFasting plasma glucoseMedian(mmol/L)Hemoglobin A1cWeightPlasma insulin111098760Median(%)987607.552.50-2.5Baseline=75 kgMean Change(kg)403020100-10-20Median Change(pmol/L)Baseline=89 pmol/LCourtesy of Dr.Amanda Adler%of patients10080604
4、0201357911Years from randomizationMIStrokeSudden deathPVDAll macrovascularRenal diseaseCancerOther specifiedUnknownTotalUKPDS Group.Lancet 1998;352:837-853.7.61.60.90.110.20.34.42.40.517.843951582251331008.01.31.60.311.20.24.42.70.218.74378260124141100Any diabetes-related*MIStrokePVD*MicrovascularUK
5、PDS Group.Lancet 1998;352:837-853.40.914.75.61.18.6 *Combined microvascular and macrovascular events*Amputation or death from PVD46.017.45.01.611.40.0290.0520.520.150.0099121625n Sulphonylurea or exogenous insulin(n=2729)MI 16%reduction(P=0.052)Stroke 11%increase(P=0.52)n Metformin in overweight sub
6、jects(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.Any diabetes-related endpointDeaths related to diabetesMyocardial infarctionStrokeMicrovascul
7、ar disease24322144370.00460.019 NS0.0130.092Adapted from UK Prospective Diabetes Study Group.BMJ 1998;317:703-713.Primary Any diabetes-related endpoint Death related to diabetes All-cause mortality Secondary Myocardial infarction Stroke Peripheral vascular disease Microvascular diseaseAdapted from U
8、K Prospective Diabetes Study Group.BMJ 1998;317:713-720.1.10(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 0.350.740.590.30Any diabetes-related endpointMyocardial infarctionStrokeMicrovascular disease121611 25 =Increase in riskAdapted from
9、UK Prospective Diabetes Study(UKPDS)Group.Lancet 1998;352:837-853;UK Prospective Diabetes Study Group.BMJ 1998;317:703-713.0.0290.052NS0.0099242144370.0046NS0.0130.092n Primary Strategy -Lower LDL cholesteroln Secondary Strategy -Raise HDL cholesterol -Lower triglyceridesn Other Approaches -Non-HDL
10、cholesterol -ApoB -RemnantsAdapted 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.Primary Prevent
11、ionAFCAPS/TexCAPSSecondary PreventionCARE4SLIPID*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
12、 Pravastatin in Ischaemic Disease(LIPID)Study Group.N Engl J Med 1998;339:1349-1357.LovastatinPravastatinSimvastatinPravastatin25%28%36%25%*150(3.9)136(3.6)186(4.8)150*(3.9)239586202782Primary PreventionAFCAPS/TexCAPSSecondary PreventionCARE4SLIPID4S-ExtendedLovastatinPravastatinSimvastatinPravastat
13、inSimvastatin43%25%(p=0.05)55%(p=0.002)19%42%(p=0.001)37%23%32%25%32%239586202782483Adapted 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)St
14、udy 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;20:614-620.00.20.40.81.4Relative Risk with 95%Confidence IntervalsTotal mortality0.61.01.2ReducedIncreasedCHD mortalitySimvastatin BetterPlacebo BetterMajor CHD ev
15、entCerebrovascular eventAny atherosclerotic eventP=0.001P=0.087P0.0001P=0.242P0.0001P=0.002P=0.097P=0.071P0.0001P=0.018No diabetesDiabetes1.00.90.80.70.60.50Proportion without Major CHD EventYears Since Randomization0123456Adapted from Pyrl et al.Diabetes Care 1997;20:614-620.Diabetes by Hx,simvasta
16、tinDiabetes by Hx,placeboNo diabetes by Hx,simvastatinNo diabetes by Hx,placeboP=0.002P=0.0001Adapted from Haffner SM et al.Arch Intern Med 1999;159:2661-26670.00.20.40.81.4Relative RiskCHD mortality(P=0.26)Total mortality(P=0.34)Revascularizations(P=0.005)Major coronary events(P=0.001)0.61.01.20.72
17、0.790.520.58Adapted from Haffner SM et al.Arch Intern Med 1999;159:2661-26670.00.20.40.81.4Relative RiskCHD mortality(P=0.007)Total mortality(P=0.02)Revascularizations(P=0.01)Major coronary events(P=0.003)0.61.01.20.450.570.570.62020040060080010001200SimvastatinNormal fastingglucoseBed Days(per 100
18、Pts)Adapted from Herman WH et al.Diabetes Care 1999;22:1771-1778.55%(p0.001)PlaceboSimvastatinImpaired fastingglucosePlaceboSimvastatinPlaceboDiabetesmellitus 38%(p=0.005)28%(p0.001)Adapted from Goldberg RB et al.Circulation 1998;98:2513-2519.4535302520151050Percent with EventFollow-up Time(years)Pe
19、rcent with Event4535302520151050Follow-up Time(years)01234650123465PlaceboPravastatinPravastatinPlaceboRelative risk=0.75P=0.05Relative risk=0.77P0.001-70-60-50-40-30-20-100%Risk ReductionDowns JR et al.JAMA 1998;279:1615-1622.MenWomenOlderSmokersHTNDiabetes-37-46-31-58-38-42Adapted from Goldberg RB
20、 et al.Circulation 1998;98:2513-2519.454035302520151050Percent with EventFollow-up Time(years)Percent with EventFollow-up Time(years)01234650123465PlaceboPravastatinPravastatinPlaceboRelative risk=0.75P=0.05Relative risk=0.77P0.00145403530252015105001020304050Per-Patient%of GraftsHoogwerf BJ et al.D
21、iabetes.1999;48:1289-1294.AggressiveRxModerateRxAggressiveRxModerateRxDiabetes(n=116)No Diabetes(n=1235)Primary PreventionHelsinkiHeart StudySecondary PreventionVA-HITAdapted from Koskinen P et al.Diabetes Care 1992;15:820-825;Rubins HB et al.N Engl J Med 1999;341:410-418.Gemfibrozil(1200 mg/d)Gemfi
22、brozil(1200 mg/d)135627203(5.2)112(2.9)68%NS24%p=0.056%0510155-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(
23、n 3,000)Hypertension(n 8,000)Noncoronary vascular disease(n 7,000)Low to average blood cholesterol(n 8,000)n FPI 1996,fully enrolled,results 2001 Medical Research Council.August 1994n Primary objective:To determine whether the greater cholesterol reductions achieved with simvastatin 80 mg produce gr
24、eater CHD reductions in post-MI patients than achieved with simvastatin 20 mgn Secondary preventionn 2x2 factorial design:simvastatin 20 or 80 mg;2 mg folic acid/1 mg Vitamin B12n N=12,000n FPI 12/97,results 2003n CHD risk is extremely high in diabetic subjectsn Benefits of risk-factor modification in intervention trials also apply to subgroups with diabetesn Results of strict glycemic control on macrovascular disease are inconclusive
