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代谢综合征Update on the Metabolic Syndrome Steven Haffner, MD
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 2 Diabetes
High LDL-C
Metabolic Syndrome
At discharge
3 mo later
At discharge
High Risk of Impaired Glucose Tolerance and Type 2 Diabetes by OGTT in Post-MI Patients without Known Diabetes
IGT
% of Patients
3 mo later
New DM
35%
40%
31%
25%
n = 181
Norhammar A et al. Lancet 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 triceps skinfolds
Nondiabetic throughout the study
Prior to diagnosis of diabetes
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 Diabetes Association.
Relative Risk
1
2.82
3.71
5.02
After diagnosis of diabetes
Diabetic at baseline
Risk of Major CHD Event Associated with Insulin Quintiles in Nondiabetic Subjects: Helsinki Policemen Study
Years
5
10
20
0
15
25
Py?r?l? M et al. Circulation 1998;98:398-404.
Log rank:
Overall P = .001
Q5 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
Reprinted 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 resistance (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, 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, etc.
ATP III:  The Metabolic Syndrome Diagnosis 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.
40–49
Prevalence of the NCEP Metabolic Syndrome: NHANES III by Age
Ford ES et al. JAMA 2002;287:356-359.
Prevalence, %
20–70+
Age, years
20–29
30–39
50–59
60–69
?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 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 obesity (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 CHD:  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 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 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 <35 mg/dl (men); <40 mg/dl (women)
BMI >30 and/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 clinical 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, 1999. | 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 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 focus 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 differ 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 Disease 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 (1.98–6.43)
4
10
Cox Proportional Hazard Ratios (and 95% Confidence Intervals) Predicting All-Cause and Cardiovascular 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 S
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