1. METABOLIC Syndrome: a Global Perspective
Charles Wang, PharmD Candidate

2. Objectives Defining Metabolic Syndrome (MetS)
Factors leading to Metabolic Syndrome
Metabolic Syndrome Around the World
Treatment
Test

3. Definition Metabolic Syndrome goes by many names Metabolic syndrome X
Cardiometabolic syndrome
Syndrome X
Insulin resistance syndrome
Reaven’s syndrome (named after Gerald Reaven)
CHAOS (Australian)
Gerald Reaven American endocrinologist and professor emeritus at Stanford Univ.
He theorized that central obesity, diabetes, and HTN have common cause in insulin resistance and impaired glucose tolerance. Coined Syndrome X

4. Definition
Metabolic Syndrome is a collection of medical disorders that when occur together, increase risk of cardiovascular disease and diabetes.
Incorrectly classified as First World Problem
Can occur in any nation, regardless of wealth
All starts with obesity
Main culprit is insulin resistance
On the rise

5. Diagnosis Depends on the organization
International Diabetes Federation
Central Obesity (determined by waist circumference) AND two of the following
Triglycerides > 150 mg/dL
HDL < 40 mg/dL in males <50 mg/dL in females
Systolic >130 or diastolic >85 mmHg
FPG > 100 mg/dL
If BMI > 30 kg/m^2 central obesity is assumed
Can be previously diagnosed with hyperlipidemia, htn, or DM2

6. Diagnosis World Health Organization
Diabetes Type 1 or 2, impaired glucose tolerance, impaired fasting glucose, or insulin resistance, AND two of the following
Blood Pressure ≥ 140/90 mmHg
Dyslipidemia: TG ≥ mmol/L and HDL ≤ 0.9 mmol/L male, ≤ 1.0 mmol/L female
Central Obesity: waist:hip ratio > 0.9 in males, > 0.85 in females, or BMI > 30 kg/m^2
Microalbuminuria: excretion ratio ≥ mcg/min or albumin:creatinine ration ≥ 30 mg/g

7. Diagnosis European Group for the Study of Insulin Resistance
Requires insulin resistance defined as the top 25% of the fasting insulin values among non-DM AND two or more of the following
Central obesity: waist circumference ≥ 94 cm in males and ≥ 80 cm in females
Dyslipidemia: TG ≥ 2.0 mmol/L and/or HDL < 1
Hypertension: ≥ 140/90 mmHg
Fasting plasma glucose ≥ 6.1 mmol/L

8. Diagnosis National Cholesterol Education Program ATP III
At least 3 of the following
Central obesity: WC ≥ 40 inches in males ≥ 36 in female
Dyslipidemia: TG ≥ 150 mg/dl
HDL < 40 in males, < 50 in females
HTN: ≥ 130/85 mmHg
Fasting Plasma Glucose ≥ 110

9. Definition Diseases that encompass metabolic syndrome Australian CHAOS
Central Obesity
Insulin Resistance
Hypertension
Hyperlipidemia
Australian CHAOS
Coronary artery disease
Adult onset diabetes
Obesity
Stroke

10. Central Obesity Also known as the following
Abdominal obesity
Belly fat
It is high fat content in the abdominal areas
Excessive Visceral fat (organ fat)
Intra-abdominal fat
Located inside the peritoneal cavity
Packed in between internal organs

11. Central Obesity
Dark areas are fat. The large ring around organs is relatively benign subcutaneous fat
The Dark areas around the organs is Visceral fat and that is the bad fat.

12. Pathophysiology Red associated with insulin resistance and pathology
Green associated with normal insulin signaling, vascular protection and insulin sensitivity
Red dotted Inhibition, Green arrow stimulation
Free fatty acids, Plasminogen activator inhibitor,
Adiponectin has been shown to decrease visceral adiposity

13. Insulin Resistance Impaired fasting glucose >100 mg/dL
Impaired glucose tolerance
> 140 mg/dL for 120 minutes after ingestion of 75 grams of glucose
Elevated homeostatic model assessment of insulin resistance (HOMA-IR)
Quantifies insulin resistance and beta-cell function with formula

14. Pathophysiology Red associated with insulin resistance and pathology
Green associated with normal insulin signaling, vascular protection and insulin sensitivity
Red dotted Inhibition, Green arrow stimulation
Mitogen-activated protein kinase

15. Dyslipidemia Atherogenic dyslipidemia High plasma TG
Low HDL cholesterol levels
Increase in small dense LDL

16. Pathophysiology Insulin usually inhibits lipolysis of fat to ffa
VLDL is metabolized to remnant lipoproteins and small dense LDL. Promotes atheroma formation. TG in VLDL are transferred to HDL by Cholesterol Ester transport protein in exchange for cholesteryl esters. TG enriched HDL is cleared rapidly from circulation

17. Hypertension
Most important single, modifiable risk factor for stroke and an important risk factor for atherosclerosis and ischemic heart disease
Disease caused by endothelial dysfunction
Fails to serve its normal physiological and protective mechanisms

18. Pathophysiology Red associated with insulin resistance and pathology
Green associated with normal insulin signlaing, vascular protection and insulin sensitivity
Red dotted Inhibition, Green arrow stimulation
Endothelial nitric oxide synthase, reduction of phospho s1177=dec enos activity
Enos=regulates vasular tone and inhibits smooth muscle contraction and platelet aggreg.

19. Statistics As countries “westernize/urbanize”
Theory is mankind evolved on limited nutrition and excess causes fat storage
Increased access to food
Decreased physical activity
Sedentary lifestyle
Diet high carbohydrates
Increases in obesity, dyslipidemia, hypertension, hyperglycemia/diabetes
No longer diseases of the wealthy

20. Metabolic Syndrome Around the World
By 2025, three out of four people with diabetes will be living in third world countries.
United States
~25% have metabolic syndrome as defined by the WHO
50 million in 1990, 64 million in 2000
India
Urbanization has caused an increase in hypertension in slums and increase risk of diabetes in females with normal BMI (18-25)
~29% of the population have metabolic syndrome

21. Metabolic Syndrome Around the World
China
Overweight 26.9% in men, 31.1% in women
13.2% have metabolic syndrome
Higher in northern China than southern
Higher in urban residents vs rural
Growing rapidly due to aging population and urbanization

22. Metabolic Syndrome Around the WorldUK
Average BMI in 1970s was ~23
Average BMI in 1990s was ~26
Black 1970
White 1990

23. Metabolic Syndrome Around the World

24. Treatment Lifestyle Changes Pharmacological Interventions Lose weight
Exercise
Follow a heart healthy diet
Stop smoking
Pharmacological Interventions
Take your meds as prescribed