The Metabolic Syndrome

Gil C. Grimes, MDSeptember 2006

Objectives

Define Metabolic Syndrome Review the prevalence in our population Discuss the proposed pathophysiology Review associated morbidity and mortality Define treatment strategies

Definitions

World Health Organization Definition One of these

Insulin resistance Impaired glucose regulation

FPG ≥ 110 mg/dl and/or 2 hour PG ≥ 140 mg/dl

Two of these Hypertension SBP ≥ 140 DBP ≥ 90 Elevated Triglycerides (≥ 150 mg/dl) and/or low HDL (≤35

mg/dl males and ≤39 mg/dl females) Central Obesity waist to hip ratio >0.90 males, >0.85

females, or BMI>33 kg/m2

Microalbuminuria urinary albumin excretion rate ≥ 20 mg/min or albumin/creatinine ratio ≥ 30 mg/g

Albert KGMM et al Diabetic Med 1998;15:539-553 [Level 5]

National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATPIII) Definition

Three of the following Abdominal circumference

Men > 40 inches Women >35 inches

Triglycerides > 150 mg/dl HDL Cholesterol

Men < 40 mg/dl Women <50 mg/dl

Blood Pressure > 130/85 mm Hg Glycemia >110mg/dl

Expert panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, JAMA 2001;285:2486-2497[Level 5]

Prevalence

Obesity US 1991

[Level 2b]

Obesity US 1992

[Level 2b]

Obesity US 1993

[Level 2b]

Obesity US 1994

[Level 2b]

Obesity US 1995

[Level 2b]

Obesity US 1996

[Level 2b]

Obesity US 1997

[Level 2b]

Obesity US 1998

[Level 2b]

Obesity US 1999

[Level 2b]

Obesity US 2000

[Level 2b]

Obesity US 2001

[Level 2b]

Texas 2001

0%

5%

10%

15%

20%

25%

30%

35%

40%

45%

White Black Hispanic Multiracial Other

Pe

rce

nta

ge

Ov

erw

eig

ht

an

d O

be

se

Overweight

Obese

Behavioral Risk Factor Surveillance System, 2001 CDC [Level 2b]

0

5

10

15

20

25

30

35

Men Women Men Women Men Women

White Non-hispanic white Mexican American

Framingham Offspring San Antonio Heart Studies

Per

cen

tag

e w

ith

Met

abo

lic

Syn

dro

me

NCEP ATPIII

NCEP ATPIII BMI

WHO

Prevalence in FOS and SAHS populations

Meigs J et al Diabetes 2003; 52:2160-7 [Level 2c]

Prevalence Metabolic Syndrome in NHANES III

Ford ES et al JAMA 2002;287:356-359 [Level 2 c]

Prevalence Metabolic Syndrome in NHANES III by Race

Ford ES et al JAMA 2002;287:356-359 [Level 2 c]

Prevalence in Adolescents from NHANES III

0

1

2

3

4

5

6

7

Perc

en

tag

e w

ith

Meta

bo

lic S

yn

dro

me

Three Risk Factors

Four Risk Factors

Cook S et al Arch Pediatric Adolec Med 2003;157:821-827 [Level 2c]

Pathophysiology

Proposed Pathophysiology Role of adipose tissue

and inflammation IL-6 (pro-inflammatory

compound) Produces 25% of IL-6 Stimulate acute phase

hepatic protein production

Obesity associated with increased C-reactive protein

Represents chronic low level inflammation

More related to Waist to hip ratio than BMI

Visser M et al JAMA 1999;282:2131-2135 [Level 2b]

CRP and BMI

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

Men Women

Od

ds

ra

tio

fo

r e

lev

ate

d C

RP

Per SD increment BMI

Per SD increment waist hipratio

Visser M et al JAMA 1999;282:2131-2135 [Level 2b]

CRP, IL-6, and subsequent DM

Pradhan AD et al JAMA 2001;286:327-334 [Level 2b]

Cartoon of mechanism of disease

Associated Morbidity and Mortality

CHD Morbidity and Mortality

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

NCEP With Waist>102 cm

NCEP with Waist >94cm

WHO Waist to Hip>0.90

WHO Waist >94 cm

Re

lati

ve

ris

k o

f d

ea

th f

rom

CH

D

Age Adjusted

Age, LDL, Smoking, FHx Adjusted

Age, LDL, Smoking, FHx, SocioeconomicAdjusted

Lakka H et al JAMA 2002; 288:2709-2016 [Level 1b]

Metabolic Syndrome as a Risk for CHD and Diabetes

0

0.5

1

1.5

2

2.5

3

3.5

4

MetabolicSyndrome

Age 10 yr Smoker Pravastatin

Predictors of CHD and DM

Ha

zard

Ra

tio

CHD Univariate

CHD Multivariate

Diabetes Univariate

Sattar N et al Circulation 2003:108:414-9 [Level 2b]

Risks for CHD and CVA Morbidity

Isomaa B et al Diabetes Care 2001;24:683-689 [Level 2b]

0.00%

1.00%

2.00%

3.00%

4.00%

5.00%

6.00%

7.00%

8.00%

9.00%

10.00%

With Metabolic Syndrome Without Metabolic Synd.

Pre

va

len

ce

Mo

rbid

ity

CHDCVA

Risk for CHD Mortality

0%

2%

4%

6%

8%

10%

12%

14%

16%

18%

20%

With Metabolic Syndrome Without Metabolic Synd.

Pre

va

len

ce

Mo

rta

lity

Total Mortality

CHD Mortality

Isomaa B et al Diabetes Care 2001;24:683-689 [Level 1a]

Risk for CHD and Diabetes

Sattar N et al Circulation 2003:108:414-9 [Level 2b]

11.79

2.253.19 3.65

1

2.36

4.5

7.26

24.4

0

5

10

15

20

25

0 1 2 3 >4

Number of Metabolic Risk Factors

Haz

ard

Rat

io

CHD

Diabetes

Risk for DM from Kuopio IHD Risk Factor Study Presence of Metabolic Syndrome

Odds Ratio of developing DM 10 4 fold increased risk for DM WHO Definition with Waist Hip Ratio

>0.90 Sensitivity 0.83 Specificity 0.78

NCEP Definition Sensitivity 0.57 Specificity 0.90

Laaksonen D et al Am J Epidemiol 2002;156:1070-1077 [Level 2b]

Treatment

Treatment Prevention is the Key

Diminish the adipose poisoning Must extrapolate from other studies Diabetes Prevention Program

Goal 150 minutes of exercise weekly Low fat diet

Nutrition counseling every 90 days NNT 8 people for 3 years to prevent 1

new DM Absolute Risk Reduction 12.77%

Tuomilheto J et al NEJM 2001;344:1343-1350 [Level 1a]

Treatment Lifestyle vs. Metformin Similar design NNT for 3 years to prevent on case

of DM Lifestyle 6.9 Metformin 13.9

Diabetes Prevention Program Group NEJM 2002;346:393-403 [Level 1a]

Treatment Lifestyle vs. Xenical Subgroup analysis of Xenical trial 40% of patients positive for

Metabolic syndrome Type II DM 13.9% lifestyle group Type II DM 9.8% Xenical group Industry sponsored study

Torgerson J et al 12th European Congress on Obesity 2003 [Level 2b ?]

Statins et al Presence of Metabolic Syndrome

indicates at least 2 risk factors LDL goal <100 mg/dl Statins reduce LDL on average 18-55% Fenofibrate reduce Triglycerides 20-50%

and raise HDL 10-35% Niacin reduce LDL 5-25% Triglycerides 20-

50% and raise HDL 15-35% Combinations work well, caution for

increased risk of adverse events

O‘Mara NB Prescriber’s Letter 2003;19:191001

Control the Pressure JNC 7 guidelines and ALLHAT tell

us to lower the pressure Intensive lifestyle modification HOPE trial 32% reduction in new

onset DM for ramipril LIFE trial

Losartan 6% developed DM Atenolol 8% developed DM

Aspirin Therapy Routine recommendation for those

at increased risk for cardiovascular disease

Unclear if it decreases progression of Metabolic Syndrome

Use based on High Risk status of these patients

Sample Patient 38 year old male Weight 250 lbs Height 72 inches BMI 34 BP 140/86Screen Glucose?Screen Lipids?Therapy?

Take Home It is common in our patients The prevalence is expected to

increase The process starts early The intervention needs to start

early Get your patients up and moving