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Metabolic Syndrome

Definition Acanthosis Nigricans

Metabolic Syndrome X Brown → Black
Syndrome X Poorly Defined
Insulin Resistance Syndrome Velvety Hyperpigmentation of Skin
Reaven’s Syndrome Found in Body Folds
CHAOS (in Australia) (posterior, lateral folds of neck, axilla, groin, umbilicus, forehead)
• Coronary Artery Disease Age < 40 y/o
• High Blood Pressure May be Genetically Inherited
• Adult onset Diabetes Associated with Obesity, Endocrinopathies
• Obesity Caused by
• Stroke Insulin Resistance (↑ circulating insulin levels)
Combination of medical disorders Insulin spillover into skin
Aggregate of certain symptoms, signs Results in abnormal ↑ in growth (hyperplasia of skin)
↑ Risk
Coronary Heart Disease
Diseases related to Plaque Buildups in Artery Walls
(Stroke, Peripheral Vascular Disease)
Type 2 Diabetes

Symptoms, Features
Abdominal Obesity Xanthelasmata, Xanthoma
Excessive fat tissue in, around abdomen Signs of Dyslipidaemia
Atherogenic Dyslipidemia Not usually present in Metabolic Syndrome
↑ TG, ↓ HDL, ↑ LDL
Foster Plaque build-ups in Artery walls
↑ Blood Pre ssure
Insulin Resistance, Glucose I ntolerance
Prothrombin state
↑ Fibrinogen, Plasminogen AcƟvator Inhibitor-1 in Blood
Proinflammatory state
↑ C-Reactive Protein in Blood
Hyperuricaemia
Fatty Liver
Especially in concurrent obesity
Polycystic Ovarian Syndrome
Women
Acanthosis Nigricans Non-Alcoholi c Fatty Liver
Consistently associated with Insulin Resistance
Abdominal (Central) Obesity Other associated variables
Visceral Type 2 DM
Male pattern Obesity
Apple-shaped adiposity Dyslipidaemia
Overweight with fat deposits around Insulin Resistance ca use Fat Accumulation in 3 mechanisms
waist Impaired in Oxidation of Fatty Acids
↑ Synthesis, Uptake of Fatty Acids
↓ Hepatic secretion of VLD Lipoprotein Cholesterol

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
Polycystic Ovarian Syndrome
Glucose levels – 7.8 – 11.0 mmol/L (75g oral glucose tolerance test)
Multiple cystic follicles in Ovary
Fasting Glucose
Affect approximately 5-15% of women of reproductive age (12-45 y/o)
• Normal
Principal Features
• Mildly ↑ Obesity
Often associated with Insulin Resistance
Anovulation (results in irregular menstruation)
↑ Risk of Cardiovascular pathology
Acne
May precede Type 2 Diabetes Mellitus by many years Excessive amounts, Effe cts of Androgenic hor mones (musculinizing)
Causes (Unkn own)
Insulin Resistance Insulin Resistance
Caused by Diabetes
Specific Genes Obesity
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
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Diagnosis (Guidelines ) Risk Factors

WHO Stress
World Health Organization Criteria (1999) Upset Hormonal Balance (HPA-Axis )
NCEP-ATP III ↑ Cortisol Levels
US National Cholesterol Education Program Adult Treatment Panel III ↑ Glucose, Insulin
IDF Insulin-mediated effects on Adipose Tissue
International Diabetes Federation concensu s worldwide definition of metabolic Promote
syndrome (2006) • Visceral Adiposity
WHO ATP III IDF • Insulin Resistance
Central Obesity √ √ √ • Dyslipidaemia
↑ BP √ √ √ • Hypertension
↑ TG √ √ √ Overweight, Obesity
↓ HDL √ √ √ Central adiposity
↑ FPG (Fasting Plasma Glucose) √ √ Sedentary Lifestyle
Microalbuminuria √ ↑ Adipose Tissue (central)
Criterias for Diagnosis Presence of Any 3 Cr iterias Central Obe sity ↓ HDL Cholesterol
DM, Glucose AND ↑ TG
Intolerance, Any 2 Cr iterias
Insulin Resi stance ↑ BP
AND ↑ Glucose
Any 2 Cr iterias Aging
Diabetes Mellitus
Epidemiology Type 2 Diabetes
3rd National Health & Nutrition Examination Survey (NHANLS III) Criteria Impaired Glucose Tolerance (IGT)
47 million people have Metabolic Syndrome Coronary Heart Disease
Including 44% of those in > 50 y/o group Lipodystrophy
Metabolic Syndrome present in Genetic
10% Women, 15% Men with Normal Glucose Tolerance Acquired
42% Women, 64% Men with Impaired Fasting Glucose
78% Women, 74% Men with Type 2 Diabetes Metabolic Syndrome ↑ Risk for CVS Disease
Most Patients (>80%) with Type 2 Diabetes have Metabolic Syndrome Caused by
(converse in not necessarily true) Hypertension
Affects 1 in 5 people Dyslipidaemia
Prevalence ↑ with Age Hyperglycaemia
Hypertension
Etiology ↙ ↘
Weight (Obese) Vascular Damage, Endothelium Injury ↑ Peripheral Resistance
Genetics ↓ ↓
Atherosclerosis ↑ Heart Workload
Aging ↓ ↓
Sedentary Lifestyle (↓ Physical activity, ↑ Caloric Intake) Aneurysms Cardiac Muscles Hypertrophy
Insulin Resistance Thrombosis ↓
Stress Embolism Heart Failure
Stenosis
Adipose Tissue ↓
Myocardial Infarction
Storage depot of Fat Stroke
Secretes Cytokines Renal Artery S tenosis
When there is Obesity (Marked ↑ in Adipose Tissue) Dyslipidaemia
↑ Systemic Inflammation markers ↙ ↘
↑ C-Reactive Protein Accumulation of Lipoproteins in Impair Endothelial cell function by
↑ Fibrinogen Vessel Wall, Macrophages ↑ ROS local production
↘ ↙
↑ IL-6 Atherosclerosis
↑ TNF-α ↓
Aneurysm
Pathophysiol ogy (Insulin Resistance in Metabolic Syndrome) Thrombosis
Lack of Exercise Embolism
Uncontrolled Diet Stenosis
↓
↓
Myocardial Infarction
Obesity Stroke
↙ ↘ Renal Artery S tenosis
Excess circulating FFA deposited in Adipose Tissue release Hyperglyc aemia
Muscle, Liver Tissues Adipocytokines ↙ ↓ ↘
Intracellular TG ↑ markedly (Leptin, Adiponectin, Resistin) Non-Enzymatic Activation of Intracellular
↓ ↓ Glycosylation Protein Kinase C Hyperglyc aemia with
↓ ↓ distrubances in
Potent Inhibitors In Obesity state
AGE Formation Include production of Polyol Pathway
(Insulin Signalling) ↓ Adiponectin Accumulate at Vessel Wall Proangiogenic, ↓
Intracellular TG ↑ Resistin ↓ Profibrinogenic molecules Intracellular accumulation
Products of Fatty Acid Metabolism ↓ Enhance Lipoproteins ↓ of metabolism of Sorbitol
Adiponectin (Insulin Sensitivity) Deposition ↑ Deposition of ECM, BM ↓
Resistin (Insulin Resistance ) Material ↑ Intracellular Osmolality
↙ ↑ H2O Influx
Insulin Resistance ↓ 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