1、餐后高血糖和心血餐后高血糖和心血管危险因素管危险因素The increasing global burden of diabetesPopulation aged 20 yearsKing H,et al.Diabetes Care 1998;21:141431.Developed countriesDevelopingcountriesWorldtotalPrevalence(%)0246820252000CVD drives the economic burden of type 2 diabetesCVD:cardiovascular diseaseNichols GA,Brown JB
2、.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$6,396$10,17231.9%48.1%20.
3、0%28.6%40.3%31.2%17.2%31.8%51.0%21.1%28.0%50.9%PharmacyOutpatientInpatientPathophysiology of type 2 diabetesJanka HU.Fortschr Med 1992;110:63741.Macro-vasculardiseaseInsulin sensitivityInsulin secretionPlasma glucoseMicro-vasculardiseaseImpaired glucose toleranceHyperglycemiaDiagnosing glucose intol
4、erance 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.Diagnosis Venous plasma glucose concentration (mmol/L)
5、DiabetesFPG or 7.02h-PG*11.1IGTFPG(if measured)and 7.8 and 6.1 and 7.02h-PG*(if measured)7.8FPG and 2h-PG values identify different people with diabetes2h-PG:2-hour postchallenge plasma glucose,FPG:fasting plasma glucoseDECODE Study Group.BMJ 1998;317:3715.FPG40%Both FPG and 2h-PG28%Younger,more obe
6、sepeopleOlder,leanerpeople2h-PG32%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)MealtimeglucosespikesFastinghyperglycemiaNormalCHD MORTALITY05101520258HbA1cInci
7、dence(%)ALL CHD EVENTS05101520258HbA1cIncidence(%)Kuusisto et al,1994Glycemic Control and CHDCHD MortalityAll CHD EventsDiet and exercise28.NGT-IGT-DMAny cardio-vascular eventThe Funagata Cohort PopulationInsulin sensitivityFPG=fasting plasma glucose;PPG=postprandial plasma glucose.Intensive Treatme
8、nt Policies6)48 39 (5.3)2 4 (0.Developed countriesFasting plasmaDiabetes Care,1999CVD drives the economic burden ofBody as a whole56 (7.HyperglycemiaHarris MI et al Diabetes Care,19984)260experiencedA Comparison of Hba1c Levels Achieved in the Conventional Versus Intensive Groups of Major Trials1098
9、7650 1 2 3 4 5 6 78 9 10Time from randomization(years)HbA1cDCCTKumamoto Study9876003691215Median HbA1c(%)Time from randomization(years)UKPDSConventional therapyIntensive therapy121110987650122436486072MonthsHbA1c(%)FPG=fasting plasma glucose;PPG=postprandial plasma glucose.4.85.05.25.45.65.86.06.26.
10、4HbA1c(%)6080100120140160180200Fasting/2 hour plasma glucose(mg/dl)Harris MI et al Diabetes Care,1998UKPDS 10 yr-Cohort Data:Dissociation Between FPG&HbA1CDel Prato S.2001Duration of Daily Metabolic ConditionsBFLunchDinner0:00 am4:00 amBFPostprandialPostabsorptiveFastingMonnier L,Europ J Clin Invest
11、,2000Intensive Treatment Policies DCCT Kumamoto Study UKPDS Fasting plasma glucose(mmol/l)3.9 6 2-hr pp glucose(mmol/l)10 11 Not defined Body as a whole56 (7.Study groupGlycemic Control and CHDInsulin sensitivity30%increase in the incidence of normal glucose tolerance(p0.HyperglycemiaIGT:impaired gl
12、ucose intolerance,STOP-NIDDM:Study to Prevent Non-insulin Dependent Diabetes MellitusChiasson JL,et al,Lancet 2002;359:20727.Developed countriesPrevalence(%)30%increase in the incidence of normal glucose tolerance(p0.Tominaga M et al.BMI:body mass indexChiasson JL,et al.Cardiovascular33 (4.Body as a
13、 whole56 (7.Reduction in incidenceThe Funagata Cohort Population*Cardiovascular disease0.9000.9200.9400.9600.9801.00001234567Years*Tominaga M et al.Diabetes Care,1999All causes of death0.8600.8800.9000.9200.9400.9600.9801.00001234567YearsThe Funagata Cohort PopulationAll causes of death0.8800.9000.9
14、200.9400.9600.9801.00001234567Years*Cardiovascular disease0.9400.9500.9600.9700.9800.9901.00001234567Years*Tominaga M et al.Diabetes Care,1999*1.Type 2 DM begins as a postprandial disease2.Postprandial hyperglycemia contributes to elevations in HbA1c and complications3.Treatment of postprandial hype
15、rglycemia is critical to achieving optimal outcomes in type 2 DM4.Nevertheless,treatment of postprandial hyperglycemia is inadequately addressedSTOP-NIDDMStudy to Prevent Non-insulin Dependent Diabetes MellitusSTOPNIDDMStudy designSTOPNIDDMPlacebo t.i.d.(n=715)Acarbose 100mg t.i.d.(n=714)10366121824
16、30Months1234567891011121314VisitsPlacebon=1,4293 monthsplacebo60Close-out visitt.i.d.:three times dailyChiasson JL,et al.Lancet 2002;359:20727.Acarbose reduces the risk of developing diabetesSTOPNIDDMAcarbose reduces the incidence of type 2 diabetes in individuals with IGT Based on onepositive OGTT
17、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.Acarbose has a rapid and sustained effect on diabetes risk Acarbose-associated reduction in risk of diabetes was evident aft
18、er 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 trial Results of the STOP-NIDDM show that acarbose has long-term therapeutic efficacy in individuals with IGT IGT:impaired glucose intoleran
19、ce,STOP-NIDDM:Study to Prevent Non-insulin Dependent Diabetes MellitusChiasson JL,et al,Lancet 2002;359:20727.STOPNIDDMEfficacy of acarbose is unaffected by baseline BMI or ageSTOPNIDDMBMI:body mass indexChiasson JL,et al.Lancet 2002;359:20727.p 25%0.0015 21%0.0559 31%0.008423%0.038229%0.008924%0.02
20、6930%0.011500.5 1.0 1.5 2.0FavoursacarboseOverallAge(years)55 Sex Male FemaleBMI(kg/m2)30 30FavoursplaceboReduction in incidenceAcarbose increases the reversion of IGT to NGTNGTIGTDiabetesAt baselineAcarbose group(%)Placebo group(%)324228253531At end of treatment100%*No post-randomisation dataIGT:im
21、paired glucose tolerance,NGT:normal glucose toleranceChiasson JL,et al.Lancet 2002;359:20727.STOPNIDDMAcarbose an exceptional 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
22、 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 lymphaticMetabolic and 2 (0.3)2 1 (0.1)1 nutritionalAdverse events*Acarbose(n=714)Patients Events No.(%)No.Placebo(n=715)Patients EventsNo.(%)No.STOPNIDDMAcarbose reduces the risk
23、of cardiovascular diseaseSTOPNIDDM*Reduction in risk of developing hypertensionData were analysed using the Cox 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%Reducing postprandi
24、al hyperglycaemia decreases the risk of diabetes and CVDSTOPNIDDMAcarbose treatment resulted in a 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
25、.0001)2lStatistically significant reduction in the risk of hypertension myocardial infarction any cardiovascular 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.Chinese studies support the efficacy of
26、 acarbose in patients with IGT NGT IGT DiabetesControl27.737.434.9(n=83)Diet and exercise28.147.424.6(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
27、 groupAn emerging algorithm to manage IGT Development of evidence-based systems to identify those with IGT at most risk of diabetes Lifestyle intervention as first-line therapy for high-risk population Pharmacotherapy for those who are not able to attain stable glycaemia with lifestyle intervention
28、Pharmacotherapy following lifestyle intervention failure is supported by the International Diabetes Federation IGT:impaired glucose toleranceConclusions Management of the diabetes epidemic is an urgent global priority IGT is an appropriate target for intervention to prevent diabetes Acarbose has a p
29、roven record for safe,long-term management of postprandial hyperglycaemia Acarbose is proven to reduce the risk of diabetesand cardiovascular disease STOP-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
