Metabolic Syndrome

Darwin Deen, MD, MSDarwin Deen, MD, MS

Albert Einstein College of MedicineAlbert Einstein College of Medicine

Gina Lopez, MSII Sophie Davis Gina Lopez, MSII Sophie Davis School of Biomedical EducationSchool of Biomedical Education

Definition

"Metabolic Syndrome" (also referred to as "Metabolic Syndrome" (also referred to as Syndrome X or Insulin Resistance Syndrome X or Insulin Resistance Syndrome) describes a cluster of CVD risk Syndrome) describes a cluster of CVD risk factors and metabolic alterations associated factors and metabolic alterations associated with excess fat weight.with excess fat weight.

Characterized by five major abnormalities

1.   Obesity (central body and visceral)1.   Obesity (central body and visceral)

2.   Hypertension2.   Hypertension

3.   Insulin resistance (hyperinsulinemia)3.   Insulin resistance (hyperinsulinemia)

4.   Glucose intolerance 4.   Glucose intolerance

5. Dyslipidaemia5. Dyslipidaemia

WHO Definition

The presence of Type 2 DM, impaired glucose The presence of Type 2 DM, impaired glucose tolerance, or normal glucose tolerance with insulin tolerance, or normal glucose tolerance with insulin resistance, together with two or more of the resistance, together with two or more of the following: following: 1. Elevated blood pressure 1. Elevated blood pressure 2. Abdominal obesity and/or BMI >30)2. Abdominal obesity and/or BMI >30)3. Low HDL cholesterol 3. Low HDL cholesterol 4. High triglycerides4. High triglycerides5. Microalbuminuria 5. Microalbuminuria

Additional associated abnormalities may Additional associated abnormalities may include:include: coagulation abnormalities, coagulation abnormalities, hyperurecemia, hyperurecemia, mircoalbuminuria, mircoalbuminuria, polycystic ovary syndromepolycystic ovary syndrome,, Non-alcoholic steattohepatitis (NASH)Non-alcoholic steattohepatitis (NASH)

Significance of Metabolic Syndrome Is characterized by metabolic and Is characterized by metabolic and

hemodynamic abnormalities which each hemodynamic abnormalities which each increase the risk of cardiovascular disease.increase the risk of cardiovascular disease.

When clustered together, the risk is greatly When clustered together, the risk is greatly increased!increased!

Significance of Metabolic Syndrome Is considered an independent risk factor for Is considered an independent risk factor for

cardiovascular disease.cardiovascular disease. Has been identified by NCEP ATP III as a Has been identified by NCEP ATP III as a

trigger for intensive lifestyle modification, trigger for intensive lifestyle modification, even in individuals with LDL cholesterol even in individuals with LDL cholesterol <100 mg/dL.<100 mg/dL.

Significance of Metabolic Syndrome In diabetics, there is a strong correlation between In diabetics, there is a strong correlation between

metabolic syndrome and cardiovascular diseasemetabolic syndrome and cardiovascular disease.. Metabolic syndrome patients with Type II diabetes Metabolic syndrome patients with Type II diabetes

showed a higher prevalence of microalbuminuria showed a higher prevalence of microalbuminuria or macroalbuminuriaor macroalbuminuria..

Metabolic syndrome correlates with small LDL Metabolic syndrome correlates with small LDL particle size pattern and the occurrence of particle size pattern and the occurrence of preclinical atherosclerosis.preclinical atherosclerosis.

Epidemiology of Metabolic Syndrome Estimates of the prevalence of Metabolic Estimates of the prevalence of Metabolic

Syndrome in the United States and Europe Syndrome in the United States and Europe differ depending on the populations studied differ depending on the populations studied and the definition appliedand the definition applied..

The prevalence rate of metabolic syndrome The prevalence rate of metabolic syndrome in many western countries is 25-35%.in many western countries is 25-35%.

Based on NHANES III data, prevalence in Based on NHANES III data, prevalence in the US is 22-23%.the US is 22-23%.

Body Size as a Predictor of CHD*

BMIBMI Relative RiskRelative Risk

25-2925-29 1.721.72

29-3229-32 2.612.61

>33>33 3.443.44

W:H > 1W:H > 1 1.821.82

* Rimm EB et al. Health Professionals Follow-up Study. Am J Epi 1995.

Demographics

Based on Based on data from NHANES III:data from NHANES III: There was a slightly greater prevalence There was a slightly greater prevalence

among women. among women. 24.7% of female vs. 21.7% of males 24.7% of female vs. 21.7% of males

(p=0.007)(p=0.007) Whites were at greater risk. Whites were at greater risk.

24.1% of whites, 19.3% of blacks, and 24.1% of whites, 19.3% of blacks, and 16.5% of “other races” (p=0.003)16.5% of “other races” (p=0.003)

The Etiology of MES is Poorly Understood Insulin resistance is thought to be an underlying Insulin resistance is thought to be an underlying

feature of metabolic syndromefeature of metabolic syndrome.. Individual features of metabolic syndrome are Individual features of metabolic syndrome are

partially determined by familial factors.partially determined by familial factors. The characteristic metabolic alterations are The characteristic metabolic alterations are

associated with excess fat weight.associated with excess fat weight. Models show that the cluster of variables in Models show that the cluster of variables in

metabolic syndrome is a result of multiple factors metabolic syndrome is a result of multiple factors linked by adiposity and not a single etiology.linked by adiposity and not a single etiology.

Diagnosis of Metabolic Syndrome 1.1. NCEP Operational Definition: co-occurrence of NCEP Operational Definition: co-occurrence of

any 3 of the following abnormalities:any 3 of the following abnormalities:55

1.1. High blood pressure (>130/85)High blood pressure (>130/85) Elevated fasting serum triglycerides (>150 Elevated fasting serum triglycerides (>150

mg/dL)mg/dL) Serum HDL Cholesterol <40 mg/dL (male) or Serum HDL Cholesterol <40 mg/dL (male) or

50 mg/dL (female)50 mg/dL (female) Increased abdominal circumference >102 cm Increased abdominal circumference >102 cm

(male) or >88 cm (female)(male) or >88 cm (female) Impaired fasting glucose (>110 mg/dL)Impaired fasting glucose (>110 mg/dL)

Treatment of Metabolic Syndrome Individuals with metabolic syndrome are Individuals with metabolic syndrome are

candidates for intensified therapeutic candidates for intensified therapeutic lifestyle changes.lifestyle changes.

Treatment Goals include:Treatment Goals include: LDL cholesterol reductionLDL cholesterol reduction Weight reduction Weight reduction Treatment of elevated triglycerides and Treatment of elevated triglycerides and

low HDLlow HDL

Treatment of risk factors should be prioritized The most common clinical feature of metabolic The most common clinical feature of metabolic

abnormalities is excess body fat, which is abnormalities is excess body fat, which is associated with many of the additional defining associated with many of the additional defining characteristics.characteristics. Reducing excess body fat should therefore be Reducing excess body fat should therefore be

the focus of treatment and prevention.the focus of treatment and prevention. Physical activity and diet modifications are Physical activity and diet modifications are

indicated for the long-term treatment of metabolic indicated for the long-term treatment of metabolic syndromesyndrome..

Pharmacotherapy of dyslipidemia is indicated in Pharmacotherapy of dyslipidemia is indicated in high-risk groups.high-risk groups.

ATP III Guidelines for Treatment of Metabolic Syndrome

Targeted AreaTargeted Area GoalGoal CHD and CHD risk equivalent CHD and CHD risk equivalent (10-y risk for CHD >20%)(10-y risk for CHD >20%)

<100 mg/dL<100 mg/dL

Multiple (2+) risk factors and Multiple (2+) risk factors and 10-y risk < 20%10-y risk < 20%

<130 mg/dL<130 mg/dL

Institute weight controlInstitute weight control -10% from baseline-10% from baseline Institute physical activity Institute physical activity 30 to 40 min/d for 3 30 to 40 min/d for 3

to 5 d/wkto 5 d/wk Monitor treatment of Monitor treatment of hypertensionhypertension

<130/85 mm Hg<130/85 mm Hg

Treat LDL cholesterol first

ATP III Guidelines for Treatment of Metabolic Syndrome

Targeted AreaTargeted Area GoalGoal

Goal of non-HDL Goal of non-HDL cholesterol for patients cholesterol for patients with triglyceride >200 with triglyceride >200 mg/dL and <499 mg/dLmg/dL and <499 mg/dL

High CHD risk: <130 High CHD risk: <130 mg/dLmg/dL

Intermediate CHD risk: Intermediate CHD risk: <160 mg/dL<160 mg/dL

Low CHD risk: <190 Low CHD risk: <190 mg/dLmg/dL

Treat elevated triglycerides and low HDL cholesterol

Effective Dietary Interventions

Reduce caloriesReduce calories Reduce saturated fatReduce saturated fat Increase whole grainsIncrease whole grains Increase fruits and vegetablesIncrease fruits and vegetables Eat fish 1-2 times per weekEat fish 1-2 times per week Use monounsaturated or polyunsaturated oilsUse monounsaturated or polyunsaturated oils

Olive, Canola, and PeanutOlive, Canola, and Peanut Safflower, Sunflower or Sesame seed, Corn, or Safflower, Sunflower or Sesame seed, Corn, or

Soy Soy

Fatty Acids in Oils

OilOil SaturatedSaturated PolyPoly MonoMono

CanolaCanola 6%6% 32%32% 62%62%

SafflowerSafflower 10%10% 77%77% 13%13%

SunflowerSunflower 11%11% 69%69% 20%20%

CornCorn 13%13% 62%62% 25%25%

OliveOlive 14%14% 9%9% 77%77%

SoybeanSoybean 15%15% 61%61% 24%24%

PeanutPeanut 19%19% 33%33% 49%49%

Fatty Acids in Fats

FatFat SaturatedSaturated PolyPoly MonoMono

MargarineMargarine 19%19% 32%32% 49%49%

CottonseedCottonseed 27%27% 54%54% 19%19%

ShorteningShortening 28%28% 28%28% 44%44%

Chicken fatChicken fat 31%31% 22%22% 47%47%

LardLard 41%41% 12%12% 47%47%

Beef fatBeef fat 52%52% 4%4% 44%44%

ButterButter 66%66% 4%4% 30%30%

Effects of Exercise

Physical activity level is negatively Physical activity level is negatively associated with fasting insulinassociated with fasting insulin level. level.

Regular moderate exercise promotes Regular moderate exercise promotes alterations of lipolytic enzymes and a alterations of lipolytic enzymes and a significant increase in plasma HDL.significant increase in plasma HDL.

Should include components that improve Should include components that improve cardio-respiratory fitness, muscular strength cardio-respiratory fitness, muscular strength and endurance.and endurance.

Effects of Weight loss

In a study of 43,500 women followed over In a study of 43,500 women followed over 12 years, Williamson & colleagues found a 12 years, Williamson & colleagues found a 20% reduction in mortality in those with 20% reduction in mortality in those with intentional weight loss.intentional weight loss.

Caloric Expenditure by Activity

ActivityActivity Cal/hrCal/hr

SleepSleep 8080

SittingSitting 100100

DrivingDriving 120120

FishingFishing 130130

StandingStanding 140140

HouseworkHousework 180180

ActivityActivity Cal/hrCal/hr

BikingBiking 210210

WalkingWalking 210210

GardeningGardening 220220

GolfGolf 250250

SwimmingSwimming 300300

JoggingJogging 585585