代谢综合征ppt课件.ppt

1、Update on the Metabolic SyndromeSteven Haffner, MD,天马行空官方博客： ；QQ:1318241189；QQ群：175569632,Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497.,Metabolic Syndrome Increases Risk for CHD and Type 2 Diabetes,Coronary Heart Disease,Type 2Diab

2、etes,HighLDL-C,MetabolicSyndrome,天马行空官方博客： ；QQ:1318241189；QQ群：175569632,Atdischarge,3 molater,Atdischarge,High Risk of Impaired Glucose Tolerance and Type 2 Diabetes by OGTT in Post-MI Patients without Known Diabetes,IGT,% of Patients,3 molater,New DM,35%,40%,31%,25%,n = 181,Norhammar A et al. Lance

3、t 2002;359:2140-2144.,Increased Metabolic Syndrome in Prediabetic Subjects: Baseline Risk Factors in Subjects with Normal Glucose Tolerance at Baseline according to Conversion Status at 8-Year Follow-up: San Antonio Heart Study,Haffner SM et al. JAMA 1990;263:2893-2898.,* Ratio of subscapular to tri

4、ceps skinfolds,Nondiabeticthroughout the study,Prior todiagnosis ofdiabetes,Elevated Risk of CVD Prior to Clinical Diagnosis of Type 2 Diabetes: Nurses Health Study,Copyright 2002 American Diabetes Association From Diabetes Care, Vol. 25, 2002; 1129-1134 Reprinted with permission from The American D

5、iabetes Association.,Relative Risk,1,2.82,3.71,5.02,After diagnosis ofdiabetes,Diabetic atbaseline,Risk of Major CHD Event Associated with Insulin Quintiles in Nondiabetic Subjects: Helsinki Policemen Study,Years,5,10,20,0,15,25,Pyrl M et al. Circulation 1998;98:398-404.,Log rank: Overall P = .001 Q

6、5 vs. Q1 P .001,Q1,Q2,Q3,Q4,Q5,CVD Risk Factors across HOMA-IR Quintiles: San Antonio Heart Study (Phase II),All p(trend) 0.0001; quintile cutpoints: 1.0, 1.6, 2.5, 4.8,Adjusted for age, sex, ethnicity,Copyright 2002 American Diabetes Association From Diabetes Care, Vol. 25, 2002; 1177-1184 Reprinte

7、d with permission from The American Diabetes Association.,Definitions of the Metabolic Syndrome,According to clinical outcomes According to underlying causes According to metabolic components According to clinical criteria,Definition of Metabolic Syndrome:According to Underlying Causes,Insulin resis

8、tance (1999 WHO) Insulin resistance syndrome Lifestyle: especially obesity (NCEP ATP III) Metabolic syndrome Subclinical inflammation,WHO. Definition, Diagnosis and Classification of Diabetes Mellitus and Its Complications: Report of a WHO Consultation. Geneva: WHO, 1999. | Expert Panel on Detection

9、, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497.,Therapeutic Implications: According to Underlying Causes,Insulin resistance Treat insulin resistance Lifestyle: especially obesity Prevent and treat obesity Subclinical inflammation Treat obesity Statins, TZDs,

10、 etc.,ATP III: The Metabolic SyndromeDiagnosis is established when 3 of these risk factors are present,Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497.,4049,Prevalence of the NCEP Metabolic Syndrome: NHANES III by Age,Ford ES et al. J

11、AMA 2002;287:356-359.,Prevalence, %,2070+,Age, years,2029,3039,5059,6069,70,Men Women,24%,23%,8%,6%,44%,44%,Prevalence of the NCEP Metabolic Syndrome: NHANES III by Sex and Race/Ethnicity,Prevalence, %,Men,Ford ES et al. JAMA 2002;287:356-359.,Women,25%,16%,28%,21%,23%,26%,36%,20%,Prevalence of CHD

12、by the Metabolic Syndrome and Diabetes in the NHANES Population Age 50+,CHD Prevalence,% of Population =,No MS/No DM,54.2%,MS/No DM,28.7%,DM/No MS,2.3%,DM/MS,14.8%,8.7%,13.9%,7.5%,19.2%,Alexander CM et al. Diabetes 2003;52:1210-1214.,ATP III Metabolic Syndrome:Therapeutic Implications,Focus on obesi

13、ty (especially abdominal obesity) as the underlying cause of the metabolic syndrome Therefore, prevent development of obesity in the general population Also, treat obesity in the clinical setting (NHLBI/NIDDK Obesity Education Initiative),Different Components of the NCEP Metabolic Syndrome Predict C

14、HD: NHANES,*Significant predictors of prevalent CHD,Prediction of CHD Prevalence using Multivariate Logistic Regression,Copyright 2003 American Diabetes Association From Diabetes, Vol. 52, 2003; 1210-1214 Reprinted with permission from The American Diabetes Association.,BMI per kg/m2,HDL-C per mg/dl

15、 decrease,SBP per mm Hg,FPG per mg/dl,Different Components of the NCEP Metabolic Syndrome Predict Diabetes: San Antonio Heart Study,Stern MP et al. Ann Intern Med 2002;136:575-581.,Risk of Type 2 Diabetes per Unit Change in Risk Trait Levels,8%,2%,4%,7%,WHO. Definition, Diagnosis and Classification

16、of Diabetes Mellitus and Its Complications: Report of a WHO Consultation. Geneva: WHO, 1999.,WHO Metabolic Syndrome Definition 1999: Based on Clinical Criteria,Insulin resistance (type 2 diabetes, IFG, IGT)* Plus any 2 of the following: Elevated BP (140/90 or drug Rx) Plasma TG 150 mg/dl HDL 30 and/

17、or W/H 0.9 (men), 0.85 (women) Urinary albumin 20 mg/min; Alb/Cr 30 mg/g,* Note that 1999 WHO uses hyperinsulinemic euglycemic clamp whereas 1998 WHO and EGIR use HOMA-IR.,Must Insulin Resistance be Present for a Patient to Have the Metabolic Syndrome?,WHO 1999 clinical definition Yes ATP III 2001 c

18、linical definition No, but it is usually present Multiple metabolic risk factors are sufficient Obesity can produce the metabolic syndrome without insulin resistance,WHO. Definition, Diagnosis and Classification of Diabetes Mellitus and Its Complications: Report of a WHO Consultation. Geneva: WHO, 1

19、999. | Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497.,WHO Metabolic Syndrome Definition 1999: Therapeutic Implications,Focus on insulin resistance as the underlying cause of the metabolic syndrome More emphasis on the genetic basis

20、of the metabolic syndrome rather than obesity Leads to increased thinking about the use of drugs to treat insulin resistance in patients with the metabolic syndrome,Therapeutic Implications of Definition of Metabolic Syndrome,If focus is on obesity as underlying cause Prevent and treat obesity If fo

21、cus is on insulin resistance as underlying cause Treat insulin resistance If focus is on metabolic risk factors Treat individual risk factors,Criteria for Comparing Different Definitions of Metabolic Syndrome,Risk of: CHD DM Relation to: Insulin resistance Obesity Prevalence in community could diffe

22、r by race How simple is the definition?,Intensity of Therapy Should be Proportionate to Level of Risk,What is the impact of the metabolic syndrome on health outcomes? Cardiovascular disease Type 2 diabetes,Cardiovascular Disease Mortality Increased in the Metabolic Syndrome: Kuopio Ischaemic Heart D

23、isease Risk Factor Study,Lakka HM et al. JAMA 2002;288:2709-2716.,Cumulative Hazard, %,0,2,6,8,12,Follow-up, y,YES,Metabolic Syndrome:,NO,Cardiovascular Disease Mortality RR (95% CI), 3.55 (1.986.43),4,10,Cox Proportional Hazard Ratios (and 95% Confidence Intervals) Predicting All-Cause and Cardiova

24、scular Mortality: San Antonio Heart Study 14-Year Follow-up,Hunt KJ et al. Diabetes 2003;52:A221-A222.,* Those without diabetes, cardiovascular disease, or cancer. Adjusted for age, gender, and ethnic group.,Comparison of NCEP and 1999 WHO Metabolic Syndrome to Identify Insulin-Resistant Subjects: I

25、RAS,% in Lowest Quartile of Si,Hanley AJ et al. Diabetes 2003;52:2740-2747.,Neither,NCEP Only,WHO Only,Both,Overall Hispanics Non-Hispanic whites African Americans,Relative Risk,CRP Adds Prognostic Information at All Levels of Risk as Defined by the Framingham Risk Score,1.0,hs-CRP(mg/L),Framingham

26、10-Year Risk (%),1.03.0,3.0,Ridker PM et al. N Engl J Med 2002;347:1557-1565.,10+,59,24,01,Copyright 2002 Massachusetts Medical Society. All rights reserved. Adapted with permission.,Partial Spearman Correlation Analysis of Inflammation Markers with Variables of IRS Adjusted for Age, Sex, Clinic, Et

27、hnicity, and Smoking Status: IRAS,Festa A et al. Circulation 2000;102:4247.,*P0.05, P0.005, P0.0001 CRP=C-reactive protein; IRS=insulin-resistance syndrome; WBC=white blood cell count.,0,Mean Value of Log CRP,Mean Values of CRP by Number of Metabolic Disorders (Dyslipidemia, Upper Body Adiposity, In

28、sulin Resistance, Hypertension): IRAS,Festa A et al. Circulation 2000;102:4247.,Number of Metabolic Disorders,1,2,3,4,Fibrinogen,CRP,PAI-1,Five-Year Incidence of Type 2 Diabetes Stratified by Quartiles of Inflammatory Proteins: IRAS,Incidence, %,1st,Festa A et al. Diabetes 2002;51:1131-1137.,2nd,3rd

29、,4th,Quartiles:,P=0.06,P=0.001,P=0.001,The Effect of Rosiglitazone on CRP,Haffner SM et al. Circulation 2002;106:679-684.,Rosiglitazone8 mg/d,Rosiglitazone4 mg/d,Change from Baseline to Week 26, %,Difference = 26.8 (95% CI: 39.7, 21.8),Placebo,Difference = 21.8 (95% CI: 34.7, 5.6),n=95,n=124,n=134,T

30、he Effect of Rosiglitazone on IL-6,Haffner SM et al. Circulation 2002;106:679-684.,Rosiglitazone8 mg/d,Rosiglitazone4 mg/d,Difference = 1.9 (95% CI: 11.3, 9.3),Placebo,Difference = 0.0 (95% CI: 9.0, 10.0),Change from Baseline to Week 26, %,n=91,n=120,n=132,hs-CRP (mg/L),Reduction of CRP Levels with

31、Statin Therapy (n=22),Jialal I et al. Circulation 2001;103:1933-1935.,*,*,*,Atorvastatin(10 mg/d),Simvastatin(20 mg/d),Pravastatin(40 mg/d),Baseline,* p0.025 vs. Baseline,Insulin resistance is related to increased PAI-1, fibrinogen, and CRP levels cross-sectionally Increased levels of PAI-1, CRP, an

32、d fibrinogen (weak) predict the development of type 2 diabetes. In some analyses, these associations are independent of obesity and insulin resistance Rosiglitazone, a TZD, decreases levels of PAI-1, CRP, and MMP-9,Summary,Does Lipid and Blood Pressure Therapy Work in Subjects with the Metabolic Syn

33、drome?,Diabetic subjects Blood pressure: YES Statin therapy: YES Nondiabetic subjects Little data available,CHD Prevention Trials with Statins in Diabetic Subjects: Subgroup Analyses,Downs JR et al. JAMA 1998;279:1615-1622. | HPS Collaborative Group. Lancet 2003;361:2005-2016. | Goldberg RB et al. C

34、irculation 1998;98:2513-2519. | Pyrl K et al. Diabetes Care 1997;20:614-620. | LIPID Study Group. N Engl J Med 1998;339:1349-1357. | Haffner SM et al. Arch Intern Med 1999;159:2661-2667.,Completed Clinical Trials with Antihypertensive Agents in Diabetes,Curb JD et al. JAMA 1996;276:1886-1892. | Zuan

35、etti G et al. Circulation 1997;96:4239-4245. | Staessen JA et al. Am J Cardiol 1998;82:20R22R. | Hansson L et al. Lancet 1998;351:1755-1762. | UKPDS Group. BMJ 1998;317:703-713. | Hansson L et al. Lancet 1999;353:611-616.,Isolated LDL-CRR=0.86 (0.591.26),221,“Metabolic Syndrome” in 4S,Event Rate, %,

36、Ballantyne CM et al. Circulation 2001;104:3046-3051.,Simvastatin Placebo,237,261,284,18.0,20.3,19.0,36.9,Lipid TriadRR=0.48 (0.330.69),Glycosylatedhemoglobin 6.5%,Efficacy of Multiple Risk Factor Intervention in High-Risk Subjects (Type 2 Diabetes with Microalbuminuria): Steno-2,Patients Reaching Intensive-Treatment Goals at Mean 7.8 y, (%),Gde P et al. N Engl J Med 2003;348:383-393.,Intensive Therapy,Cholesterol175 mg/dl,Triglycerides150 mg/dl,Systolic BP130 mm Hg,Diastolic BP80 mm Hg,Conventio