1、Post Prandial Hyperglycemia:A Significant Cardiovascular Risk Factor&Treatable Precedent of Type 2 DiabetesDiagnostic Criteria for Type 2 DM Pathophysiology of type 2 DMPost Prandial Hyperglycemia(PPH)and diabetic complicationsPrevention of Type 2 DMThe increasing global burden of diabetesPopulation
2、 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.Diabetes Care 2002;25:4826.Copyright 2002 American Diabetes Association;rep
3、rinted 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%20.0%28.6%40.3%31.2%17.2%31.8%51.0%21.1%28.0%50.9%PharmacyOutpatientInpatientPa
4、thophysiology of type 2 diabetesJanka HU.Fortschr Med 1992;110:63741.Macro-vasculardiseaseInsulin sensitivityInsulin secretionPlasma glucoseMicro-vasculardiseaseImpaired glucose toleranceHyperglycemiaDiagnosing glucose intolerance criteria reflect a need for early intervention*Determined post 75g gl
5、ucose 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)DiabetesFPG or 7.02h-PG*11.1IGTFPG(if measured)and 7.8 and 6.1 and 7.02h-PG*
6、(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 obesepeopleOlder,leanerpeople2h-PG32%The Relative Contribution of FPG and Mealt
7、ime Glucose Spikes to 24-hour Glycemic LevelRiddle MC.Diabetes Care 1990;13:6766863002001000Plasma glucose(mg/dl)06001200180024000600Time(hours)MealtimeglucosespikesFastinghyperglycemiaNormalCHD MORTALITY05101520258HbA1cIncidence(%)ALL CHD EVENTS05101520258HbA1cIncidence(%)Kuusisto et al,1994Glycemi
8、c Control and CHDCHD MortalityAll CHD EventsA Comparison of Hba1c Levels Achieved in the Conventional Versus Intensive Groups of Major Trials10987650 1 2 3 4 5 6 78 9 10Time from randomization(years)HbA1cDCCTKumamoto Study9876003691215Median HbA1c(%)Time from randomization(years)UKPDSConventional th
9、erapyIntensive therapy121110987650122436486072MonthsHbA1c(%)FPG=fasting plasma glucose;PPG=postprandial plasma glucose.4.85.05.25.45.65.86.06.26.4HbA1c(%)6080100120140160180200Fasting/2 hour plasma glucose(mg/dl)Harris MI et al Diabetes Care,1998UKPDS 10 yr-Cohort Data:Dissociation Between FPG&HbA1C
10、Del Prato S.2001Duration of Daily Metabolic ConditionsBFLunchDinner0:00 am4:00 amBFPostprandialPostabsorptiveFastingMonnier L,Europ J Clin Invest,2000Intensive 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 The Funaga
11、ta 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 death0.8800.9000.9200.9400.9600.9801.00001234567Years*Cardiova
12、scular 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 hyperglycemia is critical to achieving optimal o
13、utcomes 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)1036612182430Months1234567891011121314VisitsPlacebon=1,
14、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 25%p=0.0015Based on two consecutivepositive
15、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 after 1 year Acarbose significantly reduced the
16、 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 intolerance,STOP-NIDDM:Study to Prevent Non-insulin D
17、ependent 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%0.026930%0.011500.5 1.0 1.5 2.0FavoursacarboseOv
18、erallAge(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:impaired glucose tolerance,NGT:normal glucose
19、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.Adverse events 155(21.7)277 160(22.4)260experiencedBody as a whole56 (7.8)77 58 (8.1)72Cardiovascular33 (4.6)
20、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 of cardiovascular diseaseSTOPNIDDM*Reduction in risk o
21、f 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 postprandial hyperglycaemia decreases the risk of diabetes and C
22、VDSTOPNIDDMAcarbose 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(p0.0001)2lStatistically significant reduction in the ris
23、k 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.Chinese studies support the efficacy of acarbose in patients with IGT NGT IGT DiabetesControl27.737.434
24、.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 groupAn emerging algorithm to manage IGT Development of evidenc
25、e-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 Pharmacotherapy following lifestyle intervention failure is supp
26、orted 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 proven record for safe,long-term management of postprandial hyper
27、glycaemia 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
