餐后高血糖和心血管危險因素

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 diabetesPopul

2、ation 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 Asso

3、ciation; 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%20.0%28.6%40.3%31.2%17.2%31.8%51.0%21.1%28.0%50.9%PharmacyOutpatie

4、ntInpatientPathophysiology 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*Determin

5、ed 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)DiabetesFPG or 7.02h-PG* 11.1IGTFPG (if measured) and

6、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 obesepeopleOlder,leanerpeople2h-PG32%The Relati

7、ve Contribution of FPG and Mealtime Glucose Spikes to 24-hour Glycemic LevelRiddle MC. Diabetes Care 1990;13:6766863002001000Plasma glucose (mg/dl)06001200180024000600Time (hours)MealtimeglucosespikesFastinghyperglycemiaNormalKuusisto et al, 1994Glycemic Control and CHDCHD MortalityAll CHD EventsA C

8、omparison of Hba1c Levels Achieved in the Conventional Versus Intensive Groups of Major Trials1098765012345678910Time from randomization (years)HbA1cDCCTKumamoto Study9876003691215Median HbA1c (%)Time from randomization (years)UKPDSConventional therapyIntensive therapy121110987650122436486072MonthsH

9、bA1c (%)FPG = fasting plasma glucose; PPG = postprandial plasma glucose.HbA1CPPGFPG+=4.85.05.25.45.65.86.06.26.4HbA1c (%)6080100120140160180200Fasting/2 hour plasma glucose (mg/dl)Harris MI et al Diabetes Care, 1998Hba1c, Fasting and 2hr Plasma GlucoseUKPDS 10 yr-Cohort Data: Dissociation Between FP

10、G & HbA1CHbA1cFPGDel Prato S. 2001PPGDuration of Daily Metabolic ConditionsBFLunchDinner0:00 am4:00 amBFPostprandialPostabsorptiveFastingMonnier L, Europ J Clin Invest, 2000Intensive Treatment PoliciesDCCTKumamoto StudyUKPDSFasting plasma glucose (mmol/l)3.9 6.7 7.8 62-hr pp glucose (mmol/l) 10 11No

11、t definedThe Funagata Cohort Population*Tominaga M et al. Diabetes Care, 1999NGT - IFG - DMAll causes of death0.8600.8800.9000.9200.9400.9600.9801.00001234567YearsThe Funagata Cohort Population*Tominaga M et al. Diabetes Care, 1999*NGT - IGT - DMSummary 1. Type 2 DM begins as a postprandial disease2

12、. Postprandial hyperglycemia contributes to elevations in HbA1c and complications3. Treatment of postprandial hyperglycemia is critical to achieving optimal outcomes in type 2 DM4. Nevertheless, treatment of postprandial hyperglycemia is inadequately addressedSTOP-NIDDMStudy to Prevent Non-insulin D

13、ependent Diabetes MellitusSTOPNIDDMStudy 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.Acarbose reduces the risk of develop

14、ing diabetesSTOPNIDDMAcarbose 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):A1

15、04. Acarbose has a rapid 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

16、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 Dependent Diabetes MellitusChiasson JL, et al, Lancet 2002;359:20727.STOPNIDDMEfficacy of acarbose is unaffected by baseline BMI

17、 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%0.011500.51.01.52.0FavoursacarboseOverallAge (years) 55 Sex Male FemaleBMI (kg/m2) 30 30FavoursplaceboReduction in incidence Acarbose increases the reversion o

18、f 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.STOPNIDDMAcarbose an exceptional safety profile*Events startin

19、g 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)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

20、 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 of developing hypertensionData were analysed using the Cox proportional hazard modelChiasson JL,

21、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 CVDSTOPNIDDMAcarbose treatment resulted in a Relative risk reduction of 25% for the developme

22、nt of diabetes (p=0.0015)1Relative risk reduction of 36% using two consecutive OGTTs (p=0.0017)130% increase in the incidence of normal glucose tolerance (p0.0001)2Statistically significant reduction in the risk ofhypertensionmyocardial infarctionany cardiovascular eventCVD: cardiovascular disease,

23、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 DiabetesControl27.737.434.9 (n=83)Diet and exercise28.147.424.6 (n=60)Metformin44.443.212.4(n=88)Acarbose71

24、.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 evidence-based systems to identify those with IGT at most risk of diabetesLifestyle intervention as firs