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Metabolic Syndrome
Definition
Metabolic Syndrome X
Syndrome X
Insulin Resistance Syndrome
Reavens Syndrome
CHAOS (in Australia)

Coronary Artery Disease

High Blood Pressure

Adult onset Diabetes

Obesity

Stroke
Combination of medical disorders
Aggregate of certain symptoms, signs
Risk
Coronary Heart Disease
Diseases related to Plaque Buildups in Artery Walls
(Stroke, Peripheral Vascular Disease)
Type 2 Diabetes
Symptoms, Features
Abdominal Obesity
Excessive fat tissue in, around abdomen
Atherogenic Dyslipidemia
TG, HDL, LDL
Foster Plaque build-ups in Artery walls
Blood Pre ssure
Insulin Resistance, Glucose I ntolerance
Prothrombin state
Fibrinogen, Plasminogen Acvator Inhibitor-1 in Blood
Proinflammatory state
C-Reactive Protein in Blood
Hyperuricaemia
Fatty Liver
Especially in concurrent obesity
Polycystic Ovarian Syndrome
Women
Acanthosis Nigricans
Abdominal (Central) Obesity
Visceral
Male pattern
Apple-shaped adiposity
Overweight with fat deposits around
waist

Glucose Int olerance (Impaired Glucose Tolerance)

WHO, ADA
Intermediately Blood Glucose level 2 hours after glucose given
But less than would qualify for Type 2 Diabetes Mellitus
Glucose levels 7.8 11.0 mmol/L (75g oral glucose tolerance test)
Fasting Glucose

Normal

Mildly
Often associated with Insulin Resistance
Risk of Cardiovascular pathology
May precede Type 2 Diabetes Mellitus by many years
Insulin Resistance
Caused by
Specific Genes
Excess Weight
Lack of Physical Activity
Muscle, Fat, Liver cells do not respond properly to Insulin
(glucose uptake, metabolism, storage)
As a result, Insulin is required (Pancreas Production, eventually Fail)
Hyperglycaemia, Hyperinsulinaemia
Metabolic Syndrome
Type 2 Diabetes

Acanthosis Nigricans
Brown Black
Poorly Defined
Velvety Hyperpigmentation of Skin
Found in Body Folds
(posterior, lateral folds of neck, axilla, groin, umbilicus, forehead)
Age < 40 y/o
May be Genetically Inherited
Associated with Obesity, Endocrinopathies
Caused by
Insulin Resistance ( circulating insulin levels)
Insulin spillover into skin
Results in abnormal in growth (hyperplasia of skin)

Xanthelasmata, Xanthoma
Signs of Dyslipidaemia
Not usually present in Metabolic Syndrome

Non-Alcoholi c Fatty Liver

Consistently associated with Insulin Resistance
Other associated variables
Type 2 DM
Obesity
Dyslipidaemia
Insulin Resistance ca use Fat Accumulation in 3 mechanisms
Impaired in Oxidation of Fatty Acids
Synthesis, Uptake of Fatty Acids
Hepatic secretion of VLD Lipoprotein Cholesterol

Polycystic Ovarian Syndrome

Multiple cystic follicles in Ovary
Affect approximately 5-15% of women of reproductive age (12-45 y/o)
Principal Features
Obesity
Anovulation (results in irregular menstruation)
Acne
Excessive amounts, Effe cts of Androgenic hor mones (musculinizing)
Causes (Unkn own)
Insulin Resistance
Diabetes
Obesity

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Diagnosis (Guidelines )
WHO
World Health Organization Criteria (1999)
NCEP-ATP III
US National Cholesterol Education Program Adult Treatment Panel III
IDF
International Diabetes Federation concensu s worldwide definition of metabolic
syndrome (2006)
WHO
ATP III
IDF
Central Obesity

BP

TG

HDL

FPG (Fasting Plasma Glucose)

Microalbuminuria

Presence of
Any 3 Cr iterias
Central Obe sity
Criterias for Diagnosis
DM, Glucose
Intolerance,
Insulin Resi stance
AND
Any 2 Cr iterias

AND
Any 2 Cr iterias

Epidemiology
3rd National Health & Nutrition Examination Survey (NHANLS III) Criteria
47 million people have Metabolic Syndrome
Including 44% of those in > 50 y/o group
Metabolic Syndrome present in
10% Women, 15% Men with Normal Glucose Tolerance
42% Women, 64% Men with Impaired Fasting Glucose
78% Women, 74% Men with Type 2 Diabetes
Most Patients (>80%) with Type 2 Diabetes have Metabolic Syndrome
(converse in not necessarily true)
Affects 1 in 5 people
Prevalence with Age
Etiology
Weight (Obese)
Genetics
Aging
Sedentary Lifestyle ( Physical activity, Caloric Intake)
Insulin Resistance
Stress
Adipose Tissue
Storage depot of Fat
Secretes Cytokines
When there is Obesity (Marked in Adipose Tissue)
Systemic Inflammation markers
C-Reactive Protein
Fibrinogen
IL-6
TNF-
Pathophysiol ogy (Insulin Resistance in Metabolic Syndrome)
Lack of Exercise
Uncontrolled Diet

Obesity

Excess circulating FFA deposited in
Adipose Tissue release
Muscle, Liver Tissues
Adipocytokines
Intracellular TG markedly
(Leptin, Adiponectin, Resistin)

Potent Inhibitors
In Obesity state
(Insulin Signalling)
Adiponectin
Intracellular TG
Resistin
Products of Fatty Acid Metabolism

Adiponectin (Insulin Sensitivity)

Resistin (Insulin Resistance )

Insulin Resistance

Risk Factors
Stress
Upset Hormonal Balance (HPA-Axis )
Cortisol Levels
Glucose, Insulin
Insulin-mediated effects on Adipose Tissue
Promote

Visceral Adiposity

Insulin Resistance

Dyslipidaemia

Hypertension
Overweight, Obesity
Central adiposity
Sedentary Lifestyle
Adipose Tissue (central)
HDL Cholesterol
TG
BP
Glucose
Aging
Diabetes Mellitus
Type 2 Diabetes
Impaired Glucose Tolerance (IGT)
Coronary Heart Disease
Lipodystrophy
Genetic
Acquired
Metabolic Syndrome Risk for CVS Disease
Caused by
Hypertension
Dyslipidaemia
Hyperglycaemia
Hypertension

Vascular Damage, Endothelium Injury

Peripheral Resistance

Atherosclerosis
Heart Workload

Aneurysms
Cardiac Muscles Hypertrophy
Thrombosis

Embolism
Heart Failure
Stenosis

Myocardial Infarction
Stroke
Renal Artery S tenosis
Dyslipidaemia

Accumulation of Lipoproteins in
Impair Endothelial cell function by
Vessel Wall, Macrophages
ROS local production

Atherosclerosis

Aneurysm
Thrombosis
Embolism
Stenosis

Myocardial Infarction
Stroke
Renal Artery S tenosis
Hyperglyc aemia

Non-Enzymatic
Activation of
Intracellular
Glycosylation
Protein Kinase C
Hyperglyc aemia with

distrubances in
AGE Formation
Include production of
Polyol Pathway
Accumulate at Vessel Wall
Proangiogenic,

Profibrinogenic molecules
Intracellular accumulation
Enhance Lipoproteins

of metabolism of Sorbitol
Deposition
Deposition of ECM, BM

Material
Intracellular Osmolality
H2O Influx
Intracellular
Antioxidant Reserves

Endothelial Cell Injury

Diabetic Macrovascular Disease

Diabetic Microangiopathy
Diabetic Complications

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Prevention
Exercise
Start slowly
Gradually step up to exercising on most days of the week (30-60 mins)
Lose Weight
If Overweight
Healthy Diet
Fruits, Vegetables
Saturated Fats, Trans Fat, Cholesterol, Salt
Quit Smoking
Treatment
Change of Lifestyle
Caloric restriction
Physical activity
Drug
Hypertension Diuretics, ACE Inhibitors
LDL, TG, HDL Cholesterol Drugs
Insulin Resistance Metformin, Thiazolidinediones