1. Metabolic Syndrome Darwin Deen, MD, MS Albert Einstein College of Medicine Gina Lopez, MSII Sophie Davis School of Biomedical Education

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

3. Characterized by five major abnormalities 1. Obesity (central body and visceral) 2. Hypertension 3. Insulin resistance (hyperinsulinemia) 4. Glucose intolerance 5. Dyslipidaemia

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

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

6. Significance of Metabolic Syndrome Is characterized by metabolic and hemodynamic abnormalities which each increase the risk of cardiovascular disease. Is characterized by metabolic and hemodynamic abnormalities which each increase the risk of cardiovascular disease. When clustered together, the risk is greatly increased!

7. Significance of Metabolic Syndrome Is considered an independent risk factor for cardiovascular disease. Is considered an independent risk factor for cardiovascular disease. Has been identified by NCEP ATP III as a trigger for intensive lifestyle modification, even in individuals with LDL cholesterol <100 mg/dL. Has been identified by NCEP ATP III as a trigger for intensive lifestyle modification, even in individuals with LDL cholesterol <100 mg/dL.

8. Significance of Metabolic Syndrome In diabetics, there is a strong correlation between metabolic syndrome and cardiovascular disease. In diabetics, there is a strong correlation between metabolic syndrome and cardiovascular disease. Metabolic syndrome patients with Type II diabetes showed a higher prevalence of microalbuminuria or macroalbuminuria. Metabolic syndrome patients with Type II diabetes showed a higher prevalence of microalbuminuria or macroalbuminuria. Metabolic syndrome correlates with small LDL particle size pattern and the occurrence of preclinical atherosclerosis. Metabolic syndrome correlates with small LDL particle size pattern and the occurrence of preclinical atherosclerosis.

9. Epidemiology of Metabolic Syndrome Estimates of the prevalence of Metabolic Syndrome in the United States and Europe differ depending on the populations studied and the definition applied. Estimates of the prevalence of Metabolic Syndrome in the United States and Europe differ depending on the populations studied and the definition applied. The prevalence rate of metabolic syndrome in many western countries is 25-35%. The prevalence rate of metabolic syndrome in many western countries is 25-35%. Based on NHANES III data, prevalence in the US is 22-23%. Based on NHANES III data, prevalence in the US is 22-23%.

10. Body Size as a Predictor of CHD* BMI Relative Risk 25-291.72 29-322.61 >333.44 W:H > 1 1.82 * Rimm EB et al. Health Professionals Follow-up Study. Am J Epi 1995.

11. Demographics Based on data from NHANES III: Based on data from NHANES III:  There was a slightly greater prevalence among women.  24.7% of female vs. 21.7% of males (p=0.007)  Whites were at greater risk.  24.1% of whites, 19.3% of blacks, and 16.5% of “other races” (p=0.003)

12. The Etiology of MES is Poorly Understood Insulin resistance is thought to be an underlying feature of metabolic syndrome. Insulin resistance is thought to be an underlying feature of metabolic syndrome. Individual features of metabolic syndrome are partially determined by familial factors. Individual features of metabolic syndrome are partially determined by familial factors. The characteristic metabolic alterations are associated with excess fat weight. The characteristic metabolic alterations are associated with excess fat weight. Models show that the cluster of variables in metabolic syndrome is a result of multiple factors linked by adiposity and not a single etiology. Models show that the cluster of variables in metabolic syndrome is a result of multiple factors linked by adiposity and not a single etiology.

13. Diagnosis of Metabolic Syndrome 1. NCEP Operational Definition: co-occurrence of any 3 of the following abnormalities: 5 1. High blood pressure (>130/85)  Elevated fasting serum triglycerides (>150 mg/dL)  Serum HDL Cholesterol <40 mg/dL (male) or 50 mg/dL (female)  Increased abdominal circumference >102 cm (male) or >88 cm (female)  Impaired fasting glucose (>110 mg/dL)

14. Treatment of Metabolic Syndrome Individuals with metabolic syndrome are candidates for intensified therapeutic lifestyle changes. Individuals with metabolic syndrome are candidates for intensified therapeutic lifestyle changes. Treatment Goals include: Treatment Goals include:  LDL cholesterol reduction  Weight reduction  Treatment of elevated triglycerides and low HDL

15. Treatment of risk factors should be prioritized The most common clinical feature of metabolic abnormalities is excess body fat, which is associated with many of the additional defining characteristics. The most common clinical feature of metabolic abnormalities is excess body fat, which is associated with many of the additional defining characteristics.  Reducing excess body fat should therefore be the focus of treatment and prevention. Physical activity and diet modifications are indicated for the long-term treatment of metabolic syndrome. Physical activity and diet modifications are indicated for the long-term treatment of metabolic syndrome. Pharmacotherapy of dyslipidemia is indicated in high-risk groups. Pharmacotherapy of dyslipidemia is indicated in high-risk groups.

16. ATP III Guidelines for Treatment of Metabolic Syndrome Targeted Area Goal CHD and CHD risk equivalent (10-y risk for CHD >20%) <100 mg/dL Multiple (2+) risk factors and 10-y risk < 20% <130 mg/dL Institute weight control -10% from baseline Institute physical activity 30 to 40 min/d for 3 to 5 d/wk Monitor treatment of hypertension <130/85 mm Hg Treat LDL cholesterol first

17. ATP III Guidelines for Treatment of Metabolic Syndrome Targeted Area Goal Goal of non-HDL cholesterol for patients with triglyceride >200 mg/dL and 200 mg/dL and <499 mg/dL High CHD risk: <130 mg/dL Intermediate CHD risk: <160 mg/dL Low CHD risk: <190 mg/dL Treat elevated triglycerides and low HDL cholesterol

18. Effective Dietary Interventions Reduce calories Reduce calories Reduce saturated fat Reduce saturated fat Increase whole grains Increase whole grains Increase fruits and vegetables Increase fruits and vegetables Eat fish 1-2 times per week Eat fish 1-2 times per week Use monounsaturated or polyunsaturated oils Use monounsaturated or polyunsaturated oils  Olive, Canola, and Peanut  Safflower, Sunflower or Sesame seed, Corn, or Soy

19. Fatty Acids in Oils OilSaturatedPolyMono Canola6%32%62% Safflower10%77%13% Sunflower11%69%20% Corn13%62%25% Olive14%9%77% Soybean15%61%24% Peanut19%33%49%

20. Fatty Acids in Fats FatSaturatedPolyMono Margarine19%32%49% Cottonseed27%54%19% Shortening28%28%44% Chicken fat 31%22%47% Lard41%12%47% Beef fat 52%4%44% Butter66%4%30%

21. Effects of Exercise Physical activity level is negatively associated with fasting insulin level. Physical activity level is negatively associated with fasting insulin level. Regular moderate exercise promotes alterations of lipolytic enzymes and a significant increase in plasma HDL. Regular moderate exercise promotes alterations of lipolytic enzymes and a significant increase in plasma HDL. Should include components that improve cardio-respiratory fitness, muscular strength and endurance. Should include components that improve cardio-respiratory fitness, muscular strength and endurance.

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

23. Caloric Expenditure by Activity ActivityCal/hr Sleep80 Sitting100 Driving120 Fishing130 Standing140 Housework180ActivityCal/hrBiking210 Walking210 Gardening220 Golf250 Swimming300 Jogging585