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1、Lessons from recent research the role of postprandial hyperglycaemia in cardiovascular riskHaller H.Diabetes Res Clin Pract 1998Consequences of postprandially increased blood glucose levelsSteady stateMetabolic effectsAtherosclerosis and late complicationsEndothelial dysfunctionVascular effectsPredi
2、abetesType 2 diabetesMealNormal counter-regulationHyper-glycaemia Stress to vascular wallsThe postprandial blood glucose hypothesisTwo open questionsIs ppBG a driving forcein the pathogenesis oftype 2 diabetes?Is ppBG a driving force in thedevelopment of cardiovascular events?ppBG:postprandial blood
3、 glucoseKnowledge from DECODE and UKPDSHyperglycaemiaTotal load(HbA1c)Postprandial peaksChronicglucose toxicityAcuteglucose toxicityTissue damageDiabetescomplicationsMacroangiopathyMicroangiopathyUKPDSDECODEDECODE:Diabetes Epidemiology Collaborative Analysis of Diagnostic Criteria in Europe,UKPDS:UK
4、 Prospective Diabetes Study012345Relative riskDiabetes-free throughout study15 yearsbefore diagnosis1014.9 yearsbefore diagnosis10 yearsbefore diagnosisRelative risk of myocardial infarction or stroke and time before clinical diagnosis of diabetesHu F et al.Diabetes Care 20021.002.823.715.02Cardiova
5、scular mortality with and without previous myocardial infarctionHaffner S et al.N Engl J Med 1998MI:myocardial infarctionCardiovascular mortality7-years incidence(%)302010050n=1,373n=1,059WithoutWithWithoutWithNo diabetesDiabetesprevious MIprevious MI40Relation between postprandial blood glucose lev
6、els and cardiovascular mortalityDECODE 19991Pacific and Indian Ocean 19992Funagata Diabetes Study 19993Whitehall,Paris and Helsinki Study 19984Diabetes Intervention Study 19965The RanchoBernardo Study 19986ppBGHonolulu Heart Programme 19877CVD death4 Balkau B et al.Diabetes Care 19985 Hanefeld M et
7、al.Diabetologia 19966 Barrett-Connor E et al.Diabetes Care 19987 Donahue R.Diabetes 19871 DECODE Study Group.Lancet 19992 Shaw J et al.Diabetologia 19993 Tominaga M et al.Diabetes Care 1999Impact of postprandial blood glucose on cardiovascular mortality risk(DECODE)DECODE Study Group,Lancet 19997550
8、250100150125 Increase in cardiovascular mortality risk(%)11.1mmol/L2-Hour blood glucose7.811mmol/L7.8mmol/L4166136Fasting blood glucose 7.8mmol/L(n=1,275)Norhammar A et al.Lancet 2002Glycometabolic state of patients with an acute myocardial infarction181 patients admitted to coronary care units in S
9、weden with acute myocardial infarctionRates of IGT and undiagnosed diabetes were essentially unchanged 3 months after discharge 35%had IGT31%had undiagnosed diabetes mean age 63.5 years no previous diagnosis of diabetes blood glucose 11.1mmol/LIGT:impaired glucose toleranceVascular damage with gener
10、ation of atherosclerotic plaquesVasculotoxic consequences of postprandial blood glucose increaseGeneration of free radicals Endothelial function More agressive lipidsGlycosylation of functional proteins HDL activity NO release Vasodilation Collagen Xanthoma cell generation Growth factors Proliferati
11、on of smoothvascular muscle cells Expression of adhesion molecules Cholesterin adhesionEndothelin release Endothelial function VasoconstrictionCeriello A.Diabetes Metab Res Rev 2000Temelkova-Kurktschiev T et al.Diabetologica 1998Esposito K et al.Circulation 2002ppBG CRP:C-reactive protein,IL:interle
12、ukin,HDL:high-density lipoprotein,NO:nitric oxide,TNF-:tumour necrosis factor-Inflammatorycytokines CRP IL-6 IL-18 TNF-Plaque and risk profile impactEndothel activationHyperlipidaemiaMediaActivation of smooth muscle cellsMonocyte(macrophage)activation Xanthoma cell generationoxLDLGlycosylation of ma
13、trix proteinsSmokingHypertoniaNO NO NOEndothelinLDLMatrixEndothelium Haller H.Diabetes Praxis 1992ppBG IntimaBasal membraneLDL:low-density lipoproteinIs there a relationship between hyperinsulinaemia and the development of cardiovascular disease?Predictors of ischaemic heart disease(Quebec Cardiovas
14、cular Study)InsulinLDLcholesterolTriglyceridesHDLcholesterolApolipoprotein BTotal cholesterol HDLcholesterol ratio1.9*1.9*1.4*0.881.9*1.6*1.32.4 1.32.7 1.01.90.651.2 1.42.8 1.22.2Odds ratio*95%CIn=2,103 males.Odds ratios are expressed as the increase in the risk of ischaemic heart disease for every
15、increase of 1 SD in the variables in question.Covariates:systolic blood pressure,familyhistory of ischaemic heart disease,use of-blockers or diuretics,and plasma insulin.*p0.001,*p0.05,*p0.004Desprs J et al.N Engl J Med 1996Apolipoprotein B,ischaemic heart disease risk,and hyperinsulinaemiaDesprs J
16、et al.N Engl J Med 1996*p=0.04,*p0.00115Insulin(U/mL)1.01.83.0*9.7*3.0*11.0*024681012Odds ratio for ischaemic heart diseaseLow apolipoprotein levelHigh apolipoprotein levelChiasson JL et al.Diabetes Care 1996012468100246810121416012Pre-treatmentPost treatment*p0.01 vs pre-treatmentPlasma glucose(mmol/L)Plasma insulin(pmol/L x 10-2)HoursHoursAcarbosePlaceboEffects of acarbose on plasma glucose and insulin in response to a test meal in IGT patients*STOP-NIDDM acarbose reduces the risk of cardiovas
