1、,Epidemiology of Insulin Resistance, Diabetes Mellitus, and Coronary Heart Disease Steven Haffner, MD,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
2、Diabetes Mellitus and Hyperglycemia Plasma Glucose Concentration,7.0 (126)6.1 (110) to 7.0 (126),2-Hour Post Glucose Load,Fasting Glucose,Diabetes Mellitus Impaired Glucose Tolerance Impaired Fasting Glucose,11.1 (200) 7.8 (140) to 11.1 (200),Values are mmol/L (mg/dl),Developed,Developing,Percent,Ki
3、ng H et al. Diabetes Care 1998;21:1414-1431.,World,1995,Prevalence of Diabetes in Adult Population (Aged 20 years) by Year and Region,2000,2025,Hospitalization Costs for Chronic Complications of Diabetes in the US,American Diabetes Association. Economic Consequences of Diabetes Mellitus in the US in
4、 1997. Alexandria, VA: American Diabetes Association, 1998:1-14.,Total costs 12 billion US $ CVD accounts for 64% of total costs,Others,Ophthalmic disease,Cardiovascular disease,Renal disease,Neurologic disease,Peripheral vascular disease,Annual CHD Deaths per 1000 Persons,Kannel WB, McGee DL. JAMA
5、1979;241:2035-2038.,Framingham Study: DM and CHD Mortality 20-Year Follow-up,17,8,17,4,Men,Women,DM Non-DM,Ischemic heart disease,% of Deaths,Geiss LS et al. In: Diabetes in America. 2nd ed. 1995; chap 11.,Mortality in People with Diabetes Causes of Death,Other heart disease,Diabetes,Cancer,Stroke,I
6、nfection,Other,Mortality per 1000 person-years*,*Age-adjusted Adapted from Gu K et al. Diabetes Care 1998;21:1138-1145.,Mortality Due to Heart Disease in Men and Women with or without Diabetes (US),29.9,19.2,Men,Women,Diabetes No Diabetes,All heart disease,Ischemic heart disease,Men,Women,11.5,6.3,2
7、3.0,7.1,11.0,3.6,Nondiabetes,Diabetes,*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 Disease in NHANES Subjects with and without Diabetes*,17.0,6.8,-16.6%,+1
8、0.7%,Men, cohort 1* Men, cohort 2* Women, cohort 1* Women, cohort 2*,-43.8%,-20.4%,14.2,7.6,7.4,4.2,2.4,1.9,(P=0.46),(P=0.76),(P0.001),(P=0.12),Rate per 1000 person-years,WOMEN,MEN,Survival Post-MI in Diabetic and Nondiabetic Men and Women: Minnesota Heart Survey,Adapted from Sprafka JM et al. Diabe
9、tes Care 1991;14:537-543.,100 80 60 40 0,Survival (%),Months Post-MI,No diabetes,n=228,n=1628,Months Post-MI,Survival (%),0,20,40,60,Diabetes,100 80 60 40 0,80,0,20,40,60,80,Diabetes,No diabetes,n=156,n=568,WOMEN,MEN,Cardiovascular Mortality in People with Diabetes,% of Deaths (Crude Rate),Adapted f
10、rom Miettinen H et al. Diabetes Care. 1998;21:69-75.,Diabetes,No Diabetes,28.6,22.1,10.9,11.9,Diabetes,No Diabetes,15.4,9.6,22.7,9.0,9.1,4.2,11.1,2.8,28 d 1 y Hospitalization 28 d Out of Hospital,Influence of Multiple Risk Factors* on CVD Death Rates in Diabetic and Nondiabetic Men: MRFIT Screenees,
11、None,One only,Age-adjusted CVD death rate per 10,000 person-years,*Serum cholesterol 200 mg/dl, smoking, SBP 120 mmHg Stamler J et al. Diabetes Care 1993;16:434-444,All three,No diabetes,Diabetes,Two only,Putative Mechanism for Increased Atherosclerosis in Type 2 Diabetes,BLACK BOX,Dyslipidemia Hype
12、rtension Hyperinsulinemia/insulin resistance Hemostatic abnormalities Hyperglycemia AGE proteins Oxidative stress,AGE = advanced glycation end products Adapted from Bierman EL. Arterioscler Thromb 1992;12:647-656.,+ = moderately increased compared with nondiabetic population + = markedly increased c
13、ompared with nondiabetic population = not different compared with nondiabetic population,Prevalence of Cardiovascular Risk Factors in Diabetic Subjects Relative to Nondiabetics,Type 1,Dyslipidemia Hypertriglyceridemia Low HDL Small, dense LDL Increased apo B Hypertension Hyperinsulinemia/insulin res
14、istance Central obesity Family history of atherosclerosis Cigarette smoking,Adapted from Chait A, Bierman EL. In: Joslins Diabetes Mellitus. Philadelphia: Lea & Febiger, 1994:648-664.,Type 2,Risk Factor,+ + ,+ + + + + + + + ,Differences in HDL Cholesterol and LDL Size by Diabetic Status in Women and
15、 Men,Howard BV et al. Diabetes Care 1998; 21:1258-1265.,0 -2 -4 -6 -8,Differences between participants with and without diabetes,HDL Cholesterol,LDL Size,0 -2 -4 -6 -8,mg/dL,Women Men,Women Men,Strategies for Reduction of Diabetic Complications,Microvascular complications - Aggressive screening - Im
16、proved metabolic control Macrovascular complications - Improved glycemic control (positive but minor) - Prevention of type 2 diabetes - Aggressive treatment of established CVRF in diabetic and possibly prediabetic subjects - Diabetic agents that improve cardiovascular risk,Incidence Rates of MI and
17、Microvascular Endpoints by Mean Systolic Blood Pressure: UKPDS,110,120,130,140,150,160,170,Incidence 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 group,Myocardial Infarction,Microvascular Endpoints,Incid
18、ence Rates of MI and Microvascular Endpoints by Mean Hemoglobin A1c: UKPDS,5,6,7,8,9,10,11,Incidence per 1000 Person Years (%),Stratton IM et al. BMJ 2000;321:405-412.,Updated Mean Hemoglobin A1c Concentration (%),Adjusted for age, sex, and ethnic group,Myocardial Infarction,Microvascular Endpoints,
19、Plasma Insulin and Triglycerides Predict Ischemic Heart Disease: Quebec Cardiovascular Study,Despres JP et al. N Engl J Med 1996;334:952-957.,Odds Ratio,12,12-15,15,F-Insulin (U/ml),4.6,p=0.005,150 mg/dl,150 mg/dl,Triglycerides,1.0,1.5,5.3,p=0.001,P0.001,6.7,5.4,P=0.002,Plasma Insulin and Apolipopro
20、tein B Predict Ischemic Heart Disease: Quebec Cardiovascular Study,Despres JP et al. N Engl J Med 1996;334:952-957.,Odds Ratio,12,12-15,15,F-Insulin (U/ml),3.0,p=0.04,119 mg/dl,119 mg/dl,Apolipoprotein B,1.0,1.5,3.2,p0.001,11.0,9.7,P0.001,p=0.04,LDL Particle Size and Apolipoprotein B Predict Ischemi
21、c Heart Disease: Quebec Cardiovascular Study,Lamarche B et al. Circulation 1997;95:69-75.,25.64,25.64,LDL Peak Particle Diameter (nm),1.0,1.0,6.2,(p0.001),Apo B,120 mg/dl,2.0,120 mg/dl,Baseline Anthropometric Variables and Cardiovascular Risk Factors in Subjects with Normal Glucose Tolerance at Base
22、line According to Conversion Status at 8-Year Follow-up: San Antonio Heart Study,BMI (kg/m2) Centrality* TG (mmol) HDLC (mmol) SBP (mmHg) Fasting glucose (mmol) Fasting insulin (pmol),Haffner SM et al. JAMA 1990;263:2893-2898.,28.2 + 1.1 1.38 + 0.09 1.83 + 0.12 1.14 + 0.07 116.8 + 3.0 5.28 + 0.1 157
23、 + 27,27.2 + 0.2 1.16 + 0.2 1.26 + 0.10 1.28 + 0.02 108.8 + 0.8 5.00 + 0.02 81 + 5,.472 .472 .006 .045 .004 .032 .006,Conversion Status at Follow-up,Diabetes (n=18),Normal (n=490),P,* Ratio of subscapular to triceps skinfolds,“Ticking Clock” Hypothesis,WHO. Diabetologia 1985;28:615-640; Haffner SM e
24、t al. JAMA 1990;263:2893-2898.,For Microvascular complications Macrovascular complications,The “clock starts ticking” At onset of hyperglycemia Before the diagnosis of hyperglycemia,Hemoglobin A1,Fasting Glucose,The 7-Year Age-Adjusted Incidence of CHD Mortality and All CHD Events: East-West Study,L
25、ehto S et al. Diabetes 1997;46:1354-1359.,40 30 20 10 0,% Incidence,P-glucose (mmol/L),9.6,9.6-13.4,13.4,40 30 20 10 0,% Incidence,CHD Mortality All CHD Events,CHD Mortality All CHD Events,HbA1 (%),8.9,8.9-10.7,10.7,Stepwise Selection of Risk Factors* in 2693 White Patients with Type 2 Diabetes with
26、 Dependent Variable as Time to First Event: UKPDS,Variable Low-Density Lipoprotein Cholesterol High-Density Lipoprotein Cholesterol Hemoglobin A1c Systolic Blood Pressure Smoking,P Value 0.00010.00010.00220.0065 0.056,Coronary Artery Disease (n=280),Position in Model First Second Third Fourth Fifth,
27、*Adjusted for age and sex. Turner RC et al. BMJ 1998;316:823-828.,Criteria for Accepting Cardiovascular Risk Factor Management as Similar in Diabetic and CHD Subjects,The risk of vascular disease is similar in diabetic subjects without pre-existing vascular disease as in nondiabetic subjects with va
28、scular disease Glycemia alone will not completely eliminate the excess of CHD risk in diabetic subjects Lipid interventions to reduce CHD can be equally effective in diabetic and nondiabetic subjects,Incidence of Fatal or Nonfatal MI During a 7-Year Follow-up in Relation to History of MI in Nondiabe
29、tic vs Diabetic Subjects: East-West Study,Incidence During Follow-up (%),(n=69),Nondiabetics with prior MI Nondiabetics with no prior MI Diabetics with prior MI Diabetics with no prior MI,18.8,Haffner SM et al. N Engl J Med 1998;339:229-234.,(n=1304),(n=169),(n=890),3.0,0.5,7.8,3.2,3.5,45.0,20.2,Eve
30、nts per 100 person-yr:,P0.001,p0.001,Incidence of Fatal or Nonfatal Stroke During a 7-Year Follow-up in Relation to History of MI in Nondiabetic vs Diabetic Subjects: East-West Study,Incidence During Follow-up (%),(n=69),Nondiabetics with prior MI Nondiabetics with no prior MI Diabetics with prior M
31、I Diabetics with no prior MI,7.2,Haffner SM et al. N Engl J Med 1998;339:229-234.,(n=1304),(n=169),(n=890),1.2,0.3,3.4,1.6,1.9,19.5,10.3,Events per 100 person-yr:,P=0.01,p0.001,Conclusions,Epidemiological data suggest that the risk of CHD in type 2 diabetes is equivalent to that in people with prevalent CHD. Although hyperglycemia is significantly related to CHD, the magnitude of association is unlikely to explain the entire excess risk of cardiovascular disease. Within type 2 diabetics, increased blood pressure and LDL-C and low HDL-C also predict the risk of future myocardial infarction.,
