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1、餐后高血糖和心血餐后高血糖和心血管危管危险因素因素本讲稿第一页，共二十九页The increasing global burden of diabetesPopulation aged 20 yearsKing H,et al.Diabetes Care 1998;21:141431.Developed countriesDevelopingcountriesWorldtotalPrevalence(%)0246820252000本讲稿第二页，共二十九页CVD drives the economic burden of type 2 diabetesCVD:cardiovascular dis
2、easeNichols GA,Brown JB.Diabetes Care 2002;25:4826.Copyright 2002 American Diabetes Association;reprinted with permission from The American Diabetes Association.1086420Cost in 1999(x1,000 US$)No CVD,no diabetesn=13,286No CVD,diabetesn=11,130CVD,no diabetesn=2,894CVD anddiabetesn=5,050$2,562$4,402$6,
3、396$10,17231.9%48.1%20.0%28.6%40.3%31.2%17.2%31.8%51.0%21.1%28.0%50.9%PharmacyOutpatientInpatient本讲稿第三页，共二十九页Pathophysiology of type 2 diabetesJanka HU.Fortschr Med 1992;110:63741.Macro-vasculardiseaseInsulin sensitivityInsulin secretionPlasma glucoseMicro-vasculardiseaseImpaired glucose toleranceHy
4、perglycemia本讲稿第四页，共二十九页Diagnosing glucose intolerance criteria reflect a need for early intervention*Determined post 75g glucose load2h-PG:2-hour postchallenge plasma glucose,FPG:fasting plasma glucose,IFG:impaired fasting glucose,IGT:impaired glucose tolerance World Health Organization,1999.Diagnos
5、is Venous plasma glucose concentration (mmol/L)DiabetesFPG or 7.02h-PG*11.1IGTFPG(if measured)and 7.8 and 6.1 and 7.02h-PG*(if measured)7.8本讲稿第五页，共二十九页FPG and 2h-PG values identify different people with diabetes2h-PG:2-hour postchallenge plasma glucose,FPG:fasting plasma glucoseDECODE Study Group.BM
6、J 1998;317:3715.FPG40%Both FPG and 2h-PG28%Younger,more obesepeopleOlder,leanerpeople2h-PG32%本讲稿第六页，共二十九页The Relative Contribution of FPG and Mealtime Glucose Spikes to 24-hour Glycemic LevelRiddle MC.Diabetes Care 1990;13:6766863002001000Plasma glucose(mg/dl)06001200180024000600Time(hours)Mealtimeg
7、lucosespikesFastinghyperglycemiaNormal本讲稿第七页，共二十九页Kuusisto et al,1994Glycemic Control and CHDCHD MortalityAll CHD Events本讲稿第八页，共二十九页A Comparison of Hba1c Levels Achieved in the Conventional Versus Intensive Groups of Major Trials1098765012345678910Time from randomization(years)HbA1cDCCTKumamoto Stud
8、y9876003691215Median HbA1c(%)Time from randomization(years)UKPDSConventional therapyIntensive therapy121110987650122436486072MonthsHbA1c(%)本讲稿第九页，共二十九页FPG=fasting plasma glucose;PPG=postprandial plasma glucose.HbA1CPPGFPG+=本讲稿第十页，共二十九页4.85.05.25.45.65.86.06.26.4HbA1c(%)6080100120140160180200Fasting/
9、2 hour plasma glucose(mg/dl)Harris MI et al Diabetes Care,1998Hba1c,Fasting and 2hr Plasma Glucose本讲稿第十一页，共二十九页UKPDS 10 yr-Cohort Data:Dissociation Between FPG&HbA1CHbAHbA1c1cFPGFPGDel Prato S.2001PPGPPG本讲稿第十二页，共二十九页Duration of Daily Metabolic ConditionsBFLunchDinner0:00 am4:00 amBFPostprandialPosta
10、bsorptiveFastingMonnier L,Europ J Clin Invest,2000本讲稿第十三页，共二十九页Intensive Treatment Policies DCCT Kumamoto Study UKPDS Fasting plasma glucose(mmol/l)3.9 6.7 7.8 6 2-hr pp glucose(mmol/l)10 11 Not defined 本讲稿第十四页，共二十九页The Funagata Cohort Population*Tominaga M et al.Diabetes Care,1999NGTNGT -IFGIFG -DM
11、DMAll causes of death0.8600.8800.9000.9200.9400.9600.9801.00001234567Years本讲稿第十五页，共二十九页The Funagata Cohort Population*Tominaga M et al.Diabetes Care,1999*NGTNGT -IGTIGT -DMDM本讲稿第十六页，共二十九页Summary 1.Type 2 DM begins as a postprandial disease2.Postprandial hyperglycemia contributes to elevations in HbA
12、1c and complications3.Treatment of postprandial hyperglycemia is critical to achieving optimal outcomes in type 2 DM4.Nevertheless,treatment of postprandial hyperglycemia is inadequately addressed本讲稿第十七页，共二十九页STOP-NIDDMStudy to Prevent Non-insulin Dependent Diabetes MellitusSTOPNIDDM本讲稿第十八页，共二十九页Stu
13、dy designSTOPNIDDMPlacebo t.i.d.(n=715)Acarbose 100mg t.i.d.(n=714)1036612182430Months1234567891011121314VisitsPlacebon=1,4293 monthsplacebo60Close-out visitt.i.d.:three times dailyChiasson JL,et al.Lancet 2002;359:20727.本讲稿第十九页，共二十九页Acarbose reduces the risk of developing diabetesSTOPNIDDMAcarbose
14、reduces the incidence of type 2 diabetes in individuals with IGT Based on onepositive OGTT 25%p=0.0015Based on two consecutivepositive OGTTs36%p=0.0017IGT:impaired glucose tolerance,OGTT:oral glucose tolerance testChiasson JL,et al.Diabetologia 2002;45(Suppl.2):A104.本讲稿第二十页，共二十九页Acarbose has a rapid
15、 and sustained effect on diabetes riskAcarbose-associated reduction in risk of diabetes was evident after 1 year Acarbose significantly reduced the risk of diabetes at each follow-up time point The beneficial effects of acarbose persisted for the duration of the trialResults of the STOP-NIDDM show t
16、hat acarbose has long-term therapeutic efficacy in individuals with IGT IGT:impaired glucose intolerance,STOP-NIDDM:Study to Prevent Non-insulin Dependent Diabetes MellitusChiasson JL,et al,Lancet 2002;359:20727.STOPNIDDM本讲稿第二十一页，共二十九页Efficacy of acarbose is unaffected by baseline BMI or ageSTOPNIDD
17、MBMI:body mass indexChiasson JL,et al.Lancet 2002;359:20727.p 25%0.0015 21%0.0559 31%0.008423%0.038229%0.008924%0.026930%0.011500.5 1.0 1.5 2.0FavoursFavoursacarboseacarboseOverallAge(years)55 Sex Male FemaleBMI(kg/m2)30 30FavoursFavoursplaceboplaceboReduction in incidence 本讲稿第二十二页，共二十九页Acarbose inc
18、reases the reversion of IGT to NGTNGTIGTDiabetesAt baselineAcarbose group(%)Placebo group(%)324228253531At end of treatment100%*No post-randomisation dataIGT:impaired glucose tolerance,NGT:normal glucose toleranceChiasson JL,et al.Lancet 2002;359:20727.STOPNIDDM本讲稿第二十三页，共二十九页Acarbose an exceptional
19、safety profile*Events starting on the first day and up to 7 days after last day of treatmentBayer AG,data on file 2002.Adverse events 155(21.7)277 160(22.4)260experiencedBody as a whole56 (7.8)77 58 (8.1)72Cardiovascular33 (4.6)48 39 (5.5)61Endocrine4 (0.6)5 5 (0.7)5Haemic2 (0.3)2 4 (0.6)4and lympha
20、ticMetabolic and 2 (0.3)2 1 (0.1)1 nutritionalAdverse events*Acarbose(n=714)Patients Events No.(%)No.Placebo(n=715)Patients EventsNo.(%)No.STOPNIDDM本讲稿第二十四页，共二十九页Acarbose reduces the risk of cardiovascular diseaseSTOPNIDDM*Reduction in risk of developing hypertensionData were analysed using the Cox
21、proportional hazard modelChiasson JL,et al.Diabetologia 2002;45(Suppl.2):A104.Hypertension*MyocardialinfarctionAny cardio-vascular eventp=0.0059p=0.0226p=0.032634%91%49%本讲稿第二十五页，共二十九页Reducing postprandial hyperglycaemia decreases the risk of diabetes and CVDSTOPNIDDMAcarbose treatment resulted in a
22、lRelative risk reduction of 25%for the development of diabetes(p=0.0015)1lRelative risk reduction of 36%using two consecutive OGTTs(p=0.0017)1l30%increase in the incidence of normal glucose tolerance(p0.0001)2lStatistically significant reduction in the risk ofhypertensionmyocardial infarctionany car
23、diovascular eventCVD:cardiovascular disease,OGTT:oral glucose tolerance test1.Chiasson JL,et al.Diabetologia 2002;45(Suppl.2):A104.2.Bayer AG,data on file 2002.本讲稿第二十六页，共二十九页Chinese studies support the efficacy of acarbose in patients with IGT NGT IGT DiabetesControl27.737.434.9(n=83)Diet and exerci
24、se28.147.424.6(n=60)Metformin44.443.212.4(n=88)Acarbose71.122.9 6.0(n=88)Percentage of patientsIGT:impaired glucose tolerance,NGT:normal glucose tolerance Wenying Y,et al.Chin J Endocrinol Metab 2001;17:1316.Study group本讲稿第二十七页，共二十九页An emerging algorithm to manage IGT Development of evidence-based s
25、ystems to identify those with IGT at most risk of diabetesLifestyle intervention as first-line therapy for high-risk populationPharmacotherapy for those who are not able to attain stable glycaemia with lifestyle interventionPharmacotherapy following lifestyle intervention failure is supported by the
26、 International Diabetes Federation IGT:impaired glucose tolerance本讲稿第二十八页，共二十九页ConclusionsManagement of the diabetes epidemic is an urgent global priorityIGT is an appropriate target for intervention to prevent diabetesAcarbose has a proven record for safe,long-term management of postprandial hyperg
27、lycaemiaAcarbose is proven to reduce the risk of diabetesand cardiovascular diseaseSTOP-NIDDM results suggest that acarbose can reduce the burden that type 2 diabetes places on individuals and society IGT:impaired glucose tolerance,STOP-NIDDM:Study to Prevent Non-insulin Dependent Diabetes Mellitus本讲稿第二十九页，共二十九页