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1、胰胰岛素抵抗糖尿病与冠素抵抗糖尿病与冠心病心病第1页，本讲稿共29页Adapted from World Health Organization.Definition,Diagnosis and Classification of Diabetes Mellitus and its Complications.Geneva:World Health Organization:1999:52.Criteria for the Diagnosis of Diabetes Mellitus and HyperglycemiaPlasma Glucose ConcentrationPlasma Glu
2、cose Concentration7.0(126)6.1(110)to 7.0(11.1(200)7.8(140)to11.1(20 years)by Year and Region20 years)by Year and Region20002025第3页，本讲稿共29页Hospitalization Costs for Chronic Complications Hospitalization Costs for Chronic Complications of Diabetes in the USof Diabetes in the USAmerican Diabetes Associ
3、ation.Economic Consequences of Diabetes Mellitusin the US in 1997.Alexandria,VA:American Diabetes Association,1998:1-14.nTotal costs 12 billion US$nCVD accounts for 64%of total costsOthersOphthalmic diseaseCardiovasculardiseaseRenal diseaseNeurologic diseasePeripheral vascular disease第4页，本讲稿共29页Annu
4、al CHD Deaths per 1000 PersonsKannel WB,McGee DL.JAMA 1979;241:2035-2038.Framingham Study:DM and CHD MortalityFramingham Study:DM and CHD Mortality20-Year Follow-up20-Year Follow-up17178 817174 4MenMenWomenWomenDMDMNon-DMNon-DM第5页，本讲稿共29页Ischemicheartdisease%of DeathsGeiss LS et al.In:Diabetes in Am
5、erica.2nd ed.1995;chap 11.Mortality in People with DiabetesMortality in People with DiabetesCauses of DeathCauses of DeathOtherheartdiseaseDiabetesCancerStrokeInfectionOther第6页，本讲稿共29页Mortality per 1000 person-years*Age-adjustedAdapted from Gu K et al.Diabetes Care 1998;21:1138-1145.Mortality Due to
6、 Heart Disease in Men and Mortality Due to Heart Disease in Men and Women with or without Diabetes(US)Women with or without Diabetes(US)29.919.2MenWomenDiabetesDiabetesNo DiabetesNo DiabetesAll heart diseaseIschemic heart diseaseMenWomen11.56.323.07.111.03.6第7页，本讲稿共29页NondiabetesNondiabetesDiabetesD
7、iabetes *Defined in 1971-1975,followed up through 1982-1984.*Defined in 1982-1984,followed up through 1992-1993.Gu K et al.JAMA 1999;281:1291-1297.Trends in Mortality Rates for Ischemic Heart Trends in Mortality Rates for Ischemic Heart Disease in NHANES Subjects with and without Disease in NHANES S
8、ubjects with and without Diabetes*Diabetes*17.06.8-16.6%-16.6%+10.7%+10.7%Men,cohort 1*Men,cohort 1*Men,cohort 2*Men,cohort 2*Women,cohort 1*Women,cohort 1*Women,cohort 2*Women,cohort 2*-43.8%-43.8%-20.4%-20.4%14.27.67.44.22.41.9(P=0.46)(P=0.76)(P200 mg/dl,smoking,SBP 120 mmHgStamler J et al.Diabete
9、s Care 1993;16:434-444All threeNo diabetesDiabetesTwo only第11页，本讲稿共29页Putative Mechanism for Increased Putative Mechanism for Increased Atherosclerosis in Type 2 DiabetesAtherosclerosis in Type 2 DiabetesBLACK BOXnDyslipidemianHypertensionnHyperinsulinemia/insulin resistancenHemostatic abnormalities
10、nHyperglycemianAGE proteinsnOxidative stressAGE=advanced glycation end productsAdapted from Bierman EL.Arterioscler Thromb 1992;12:647-656.第12页，本讲稿共29页 +=moderately increased compared with nondiabetic population+=markedly increased compared with nondiabetic population =not different compared with no
11、ndiabetic populationPrevalence of Cardiovascular Risk Factors in Prevalence of Cardiovascular Risk Factors in Diabetic Subjects Relative to NondiabeticsDiabetic Subjects Relative to NondiabeticsType 1Type 1Dyslipidemia Hypertriglyceridemia Low HDL Small,dense LDL Increased apo BHypertensionHyperinsu
12、linemia/insulin resistanceCentral obesityFamily history of atherosclerosisCigarette smokingAdapted from Chait A,Bierman EL.In:Joslins Diabetes Mellitus.Philadelphia:Lea&Febiger,1994:648-664.Type 2Type 2Risk FactorRisk Factor+第13页，本讲稿共29页Differences in HDL Cholesterol and LDL Size by Differences in H
13、DL Cholesterol and LDL Size by Diabetic Status in Women and MenDiabetic Status in Women and MenHoward BV et al.Diabetes Care 1998;21:1258-1265.0-2-4-6-8Differences between participants with and without diabetesHDL CholesterolHDL CholesterolLDL SizeLDL Size0-2-4-6-8mg/dLWomenWomenMenMenWomenWomenMenM
14、en第14页，本讲稿共29页Strategies for Reduction of Diabetic Strategies for Reduction of Diabetic ComplicationsComplicationsnMicrovascular complications-Aggressive screening-Improved metabolic controlnMacrovascular complications-Improved glycemic control(positive but minor)-Prevention of type 2 diabetes-Aggre
15、ssive treatment of established CVRF in diabetic and possibly prediabetic subjects-Diabetic agents that improve cardiovascular risk第15页，本讲稿共29页Incidence Rates of MI and Microvascular Incidence Rates of MI and Microvascular Endpoints by Mean Systolic Blood Pressure:Endpoints by Mean Systolic Blood Pre
16、ssure:UKPDSUKPDS110120130140150160170Incidence per 1000 Person Years(%)Adler AI et al.BMJ 2000;321:412-419.Updated Mean Systolic Blood Pressure(mmHg)Adjusted for age,sex,and ethnic groupMyocardial InfarctionMicrovascular Endpoints第16页，本讲稿共29页Incidence Rates of MI and Microvascular Incidence Rates of
17、 MI and Microvascular Endpoints by Mean HemoglobinEndpoints by Mean Hemoglobin AA1c:UKPDSUKPDS567891011Incidence per 1000 Person Years(%)Stratton IM et al.BMJ 2000;321:405-412.Updated Mean Hemoglobin A1c Concentration(%)Adjusted for age,sex,and ethnic groupMyocardial InfarctionMicrovascular Endpoint
18、s第17页，本讲稿共29页Plasma Insulin and Triglycerides Predict Plasma Insulin and Triglycerides Predict Ischemic Heart Disease:Ischemic Heart Disease:Quebec Cardiovascular Quebec Cardiovascular StudyStudyDespres JP et al.N Engl J Med 1996;334:952-957.Odds Ratio15F-Insulin(U/ml)4.6p=0.005150 mg/dl150 mg/dlTri
19、glycerides1.01.55.3p=0.001P0.0016.75.4P=0.002第18页，本讲稿共29页Plasma Insulin and Apolipoprotein B Predict Plasma Insulin and Apolipoprotein B Predict Ischemic Heart Disease:Ischemic Heart Disease:Quebec Cardiovascular Quebec Cardiovascular StudyStudyDespres JP et al.N Engl J Med 1996;334:952-957.Odds Rat
20、io15F-Insulin(U/ml)3.0p=0.04119 mg/dl119 mg/dlApolipoprotein B1.01.53.2p0.00111.09.7P25.6425.64LDL Peak Particle Diameter(nm)1.01.06.2(p120 mg/dl2.0120 mg/dl第20页，本讲稿共29页Baseline Anthropometric Variables and Cardiovascular Risk Baseline Anthropometric Variables and Cardiovascular Risk Factors in Subj
21、ects with Factors in Subjects with NormalNormal Glucose Tolerance at Baseline Glucose Tolerance at Baseline According to Conversion Status at 8-Year Follow-up:According to Conversion Status at 8-Year Follow-up:San Antonio San Antonio Heart StudyHeart StudyBMI(kg/m2)Centrality*TG(mmol)HDLC(mmol)SBP(m
22、mHg)Fasting glucose(mmol)Fasting insulin(pmol)Haffner SM et al.JAMA 1990;263:2893-2898.28.2+1.11.38+0.091.83+0.121.14+0.07116.8+3.05.28+0.1157+2727.2+0.21.16+0.21.26+0.101.28+0.02108.8+0.85.00+0.0281+5.472.472.006.045.004.032.006Conversion Status at Follow-upDiabetes(n=18)Diabetes(n=18)Normal(n=490)
23、Normal(n=490)P P*Ratio of subscapular to triceps skinfolds第21页，本讲稿共29页“Ticking Clock”HypothesisWHO.Diabetologia 1985;28:615-640;Haffner SM et al.JAMA 1990;263:2893-2898.ForForMicrovascular Microvascular complicationscomplicationsMacrovascular Macrovascular complicationscomplicationsThe“clock starts
24、ticking”The“clock starts ticking”At onset of hyperglycemiaAt onset of hyperglycemiaBefore the diagnosis of Before the diagnosis of hyperglycemiahyperglycemia第22页，本讲稿共29页Hemoglobin AHemoglobin A1 1Fasting GlucoseFasting GlucoseThe 7-Year Age-Adjusted Incidence of CHD The 7-Year Age-Adjusted Incidence
25、 of CHD Mortality and All CHD Events:Mortality and All CHD Events:East-West StudyEast-West StudyLehto S et al.Diabetes 1997;46:1354-1359.403020100%IncidenceP-glucose(mmol/L)13.4403020100%IncidenceCHD MortalityAll CHD EventsCHD MortalityAll CHD EventsHbA1(%)10.7第23页，本讲稿共29页Stepwise Selection of Risk
26、Factors*in 2693 White Stepwise Selection of Risk Factors*in 2693 White Patients with Type 2 Diabetes with Dependent Variable as Patients with Type 2 Diabetes with Dependent Variable as Time to First Event:Time to First Event:UKPDSUKPDS VariableVariableLow-Density Lipoprotein CholesterolHigh-Density
27、Lipoprotein CholesterolHemoglobin A1cSystolic Blood PressureSmokingP ValueP Value0.0001 0.0001 0.0022 0.00650.056Coronary Artery Disease(n=280)Position in ModelPosition in ModelFirstSecondThirdFourthFifth*Adjusted for age and sex.Turner RC et al.BMJ 1998;316:823-828.第24页，本讲稿共29页Criteria for Acceptin
28、g Cardiovascular Risk Factor Management as Similar in Diabetic and CHD SubjectsnThe risk of vascular disease is similar in diabetic subjects without pre-existing vascular disease as in nondiabetic subjects with vascular diseasenGlycemia alone will not completely eliminate the excess of CHD risk in d
29、iabetic subjectsnLipid interventions to reduce CHD can be equally effective in diabetic and nondiabetic subjects第25页，本讲稿共29页Incidence of Fatal or Nonfatal MI During a 7-Year Incidence of Fatal or Nonfatal MI During a 7-Year Follow-up in Relation to History of MI in Nondiabetic Follow-up in Relation
30、to History of MI in Nondiabetic vs Diabetic Subjects:vs Diabetic Subjects:East-West StudyEast-West StudyIncidence During Follow-up(%)(n=69)Nondiabetics with prior MINondiabetics with no prior MIDiabetics with prior MIDiabetics with no prior MI18.8Haffner SM et al.N Engl J Med 1998;339:229-234.(n=130
31、4)(n=169)(n=890)3.00.57.83.23.545.020.2Events per100 person-yr:P0.001p0.001第26页，本讲稿共29页Incidence of Fatal or Nonfatal Stroke During a Incidence of Fatal or Nonfatal Stroke During a 7-Year Follow-up in Relation to History of MI in 7-Year Follow-up in Relation to History of MI in Nondiabetic vs Diabet
32、ic Subjects:Nondiabetic vs Diabetic Subjects:East-West StudyEast-West StudyIncidence During Follow-up(%)(n=69)Nondiabetics with prior MINondiabetics with no prior MIDiabetics with prior MIDiabetics with no prior MI7.2Haffner SM et al.N Engl J Med 1998;339:229-234.(n=1304)(n=169)(n=890)1.20.33.41.61.
33、919.510.3Events per100 person-yr:P=0.01p0.001第27页，本讲稿共29页ConclusionsnEpidemiological data suggest that the risk of CHD in type 2 diabetes is equivalent to that in people with prevalent CHD.nAlthough hyperglycemia is significantly related to CHD,the magnitude of association is unlikely to explain the entire excess risk of cardiovascular disease.nWithin type 2 diabetics,increased blood pressure and LDL-C and low HDL-C also predict the risk of future myocardial infarction.第28页，本讲稿共29页第29页，本讲稿共29页