Obesity and Metabolic Syndrome
Steven M. Haffner, MD
Conceptual Framework for the Metabolic Syndrome
Environmental causes are responsible for the epidemic of the metabolic syndrome (NCEP)
Treatment: reduce obesity and increase activity
Insulin resistance is the underlying cause of the metabolic syndrome (WHO)
Treatment: a) reduce obesity and increase activity b) insulin sensitizers
Inflammation is the underlying cause of the metabolic syndrome
Treatment: a) reduce obesity and increase activity b) insulin sensitizers c) statins, ACE Inhibitors, ARBs
Metabolic Syndrome Increases Risk for CHD and Type 2 Diabetes
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497.
Coronary Heart Disease
Type 2 Diabetes
High LDL-C
Metabolic Syndrome
The Metabolic Syndrome: Historical Perspective
Reaven G. Diabetes. 1988;37:1565-1607.
Insulin Resistance
Glucose Intolerance
Hyperinsulinemia
? TG
? HDL-C
Hypertension
1988: Syndrome X
CORONARY HEART DISEASE
The Metabolic Syndrome: Current Perspective
Adapted from Reaven G. Drugs. 1999;58 (suppl):19-20
Body Size
? BMI
? Central Adiposity
Glucose Metabolism
Uric Acid Metabolism
Dyslipidemia
Hemodynamic
Novel Risk Factors
CORONARY HEART DISEASE
Insulin Resistance
Hyperinsulinemia
+
? TG
? PP lipemia
? HDL-C
? PHLA
Small, dense LDL
± Glucose intolerance
? Uric acid
? Urinary uric acid clearance
? SNS activity
? Na retention
Hypertension
? CRP
? PAI-1
? Fibrinogen
ATP III: The Metabolic Syndrome* *Diagnosis is established when >3 of these risk factors are present
* The Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497.
**The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus: Follow-up report on the diagnosis of diabetes mellitus. Diabetes Care 26:3160-3167, 2003
** 2003 New ADA IFG criteria (Expert Panel…,Diabetes Care 26:3160-3167, 2003)
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
WHO. Definition, Diagnosis and Classification of Diabetes Mellitus and Its Complications: Report of a WHO Consultation. Geneva: WHO, 1999.
IRS: AACE Criteria
Diagnosing Insulin Resistance Syndrome Is as Simple as 1 plus 2 Choose: One Risk + Two Parameters
IRS: AACE Criteria – Risks (Choose 1)
BMI >25 kg/m2
Waist circumference
Men >40”
Women >35”
Sedentary Lifestyle
Age >40
Non-Caucasian ethnicity
Family History of DM, HTM, or CVD
History of glucose intolerance or gestational diabetes
Personal Dx of HTN, TGL, low HDL or CVD
Acanthosis nigricans
Polycystic ovarian syndrome (PCOS)
Nonalcoholic fatty liver disease (NAFLD)
Cancer (obesity related)
IRS: AACE Criteria – Parameters (Choose 2)
Triglycerides >150 mg/dl
HDL cholesterol
Men <40 mg/dl
Women <50 mg/dl
Blood pressure >135/85
Blood glucose
2-hour >140 mg/dl, OR
Fasting 110 – 125 mg/dl
40–49
20–70+
Age, years
20–29
30–39
50–59
60–69
?70
Ford ES et al. JAMA 2002;287:356-359.
Prevalence, %
Men
Women
24%
23%
8%
6%
44%
44%
Prevalence of the NCEP Metabolic Syndrome: NHANES III by Age
Ford ES et al. JAMA 2002;287:356-359.
White
African American
25%
Prevalence of the NCEP Metabolic Syndrome: NHANES III by Sex and Race/Ethnicity
Men
Women
16%
28%
Mexican American
Other
21%
23%
26%
36%
20%
DM
(n=1,430)
NGT
(n=1,808)
IFG/IGT
(n=685)
All
(n=3,928)
Isomaa B et al. Diabetes Care. 2001;24:683-689.
Prevalence of CHD (%)
P=.04
Botnia Study Prevalence of CHD in Patients with the Metabolic Syndrome
9.2%
Metabolic Syndrome
4.1%
11.0%
5.3%
27.1%
P=.06
P<.001
13.5%
21.4%
P<.001
5.5%
Cardiovascular Disease Mortality Increased in the Metabolic Syndrome: Kuopio Ischemic Heart Disease Risk Factor Study
Lakka HM et al. JAMA 2002;288:2709-2716.
Cumulative Hazard, %
0
2
6
8
12
Follow-up, year
YES
Metabolic Syndrome:
NO
Cardiovascular Disease Mortality
RR (95% CI), 3.55 (1.98–6.43)
4
10
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..
NCEP vs WHO Metabolic Syndrome in Relationship to CVD Mortality: San Antonio Heart Study
n = 2,815 (age 25-64)
Both NCEP and WHO metabolic syndrome, 509
NCEP alone, n=197
WHO alone, n=199
12.7 year follow-up (229 deaths)
Three populations considered
Overall population
No CVD at baseline
No CVD or diabetes at baseline (primary prevention)
Hunt, K (Circulation, 2004; 110:1245-1251)
Hazard Ratio for CVD Mortality (SAHS): Adjusted for Age, Sex and Ethnicity
Hunt, K (Circulation, 2004; 110:1245-1251)
Hazard Ratio for CVD Mortality (SAHS): Adjusted for Age and Ethnicity 1: No CVD at Baseline
Hunt, K (Circulation, 2004; 110:1245-1251)
Hazard Ratio for CVD Mortality (SAHS): Adjusted for Age and Ethnicity 1: No CVD at Baseline
Hunt, K (Circulation, 2004; 110:1245-1251)
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.
Incident Diabetes after Stratification by Age or BMI, IGT, and the Metabolic Syndrome
Ref. Lorenzo et al, Diabetes Care, 2003, 26: 3153-3159
p<0.0001
p<0.0001
P=0.018
NCEP definition
%
Yes
No
No
Yes
IGT
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%
Comparison of NCEP and 1999 WHO Metabolic Syndrome to Identify Insulin-Resistant Subjects: IRAS
% in Lowest Quartile of Si
Hanley AJ et al. Diabetes 2003;52:2740-2747.
Overall
Hispanics
Non-Hispanic whites
African Americans
Neither
NCEP Only
WHO Only
Both
Treatment of the Metabolic Syndrome in Overweight or Obese Patients
Weight loss induced by diet and increased physical activity is the cornerstone of therapy
Weight loss induced by drug therapy can also improve specific features of the metabolic syndrome
Bariatric surgery is the most effective weight loss therapy for extremely obese subjects and improves all features of the metabolic syndrome
Treatme