Download to read offline
More Related Content
Similar to Metabolic syndrome
Metabolic syndrome
- 1. The Metabolic Syndrome TheLifestyle Disease Dr Dharmendra Kumar Dept of Physiology AFMC, Pune “... good health is more than just exercise and diet. It’s really a point of view and a mental attitude you have about yourself.” ....Albert Schweitzer
- 2. Scope • Introduction • History •Pathophysiology • Recent advances • Summary & conclusion • Take home message 2
- 3. Metabolic syndrome isalso known as: • Metabolic syndrome X • Insulin resistance syndrome • Visceral fat syndrome • Multiple risk factor clustering syndrome • Cardiometabolic syndrome • Obesity dyslipidemia syndrome • Reaven's syndrome (named for Dr. Gerald Reaven) 3
- 4. Introduction • Metabolic syndromeis a cluster of metabolic risk factors • Strongly responsible for excess of CVD morbidity among overweight and Obese patients and those with Type-2 DM. • Simple concept : • Most dangerous risk factors for CVD & Type-2 DM 4
- 5. Introduction Globally: • The NHANES1999-2002 database shows Overall prevalence 34.5% • Risk - 2 times mortality - 3 times- CVD or stroke - 5-7 times- diabetes type 2 • Prevalence increases with weight. • 5% of normal weight, 22% of overweight, and 60% of obese • Gained significant importance recently • NCEP-ATP III • An independent risk factor for CVD 5
- 6. History • 250 ysago , Morgagni : visceral fat and HTN, Atherosclerosis • First World War- metabolic abnormalities, relation b/w DM &HTN • 1920- word clustering, risk factors associated with diabetes • 1930-1950- non-communicable disease era • 1947: French Jean Vague-. Central obesity, excess fat--metabolic complications • Various term: • 1950 : Term Metabolic syndrome • 1960 : Plurimetabolic Syndrome • 1980 : Syndrome X : glucose & insulin metab + obesity • 1988: Dr Gerald Reaven’s - Insulin sensitivity - risk CHD - insulin resistance • Various definition • 1998, 2001, 2005/6, 2009 6
- 7. Definitions of theMetabolic Syndrome • According to clinical outcomes • According to underlying causes • Insulin resistance-WHO definition • Lifestyle: especially obesity- NCEP ATP III • According to metabolic components • According to clinical criteria 7
- 8. Timeline of MetabolicSyndrome Criteria • World Health Organization (1998)#* • European Group for the Study of Insulin Resistance (1999)# • National Cholesterol Education Program (2001)# • American Association of Clinical Endocrinologists (2003) • International Diabetes Federation (2005)#* • American Heart Association & NHLBI (2005)# • “Harmonized” definition (2009)# #Measure of obesity included *BMI included (nonexclusively) 8
- 9. Definitions of theMetabolic Syndrome WHO Definition : 1998 • Based on insulin resistance, BMI, Microalbuminuria NCEP ATP III : 2001 • Abdominal obesity is not an essential component • No cut-off points for WC IDF definition : 2005 • abdominal obesity an essential component • cut-off points for WC “Harmonized” definition : 2009 • Abdominal obesity is not an essential component • Most accepted 9
- 10. Metabolic syndrome: “Harmonized”definition (2009) Abdominal obesity is not an essential component Parameter: (Any three) •Waist Circumference •Triglycerides (mg/dL) •HDL (mg/dL) •Blood pressure (mmHg) •Fasting glucose (mg/dL) Limit Values: •Population specific •> 150 •Men: < 40; Women: <50 •>130/>85 •> 100 Note: Waist Circumference is the only observable parameter 10
- 11. Causative Factors inthe Metabolic Syndrome The Two significant factors : “Central Obesity” and “Insulin Resistance Other possible Factors : • Genetics • Physical inactivity • Aging • High carbohydrate diets (>60% of energy intake) • Pro inflammatory state • Hormonal state (These may play variable roles in different ethnic groups) 11
- 12. Normal Obesity Visceral FatDistribution: Normal vs Obesity Diagnosis of metabolic syndrome- visceral fat areas as determined by CT scan > 100 cm2 12
- 13. Pathophysiology 1. Insulin Resistance 2.Visceral adiposity 3. Dyslipidemia 4. Glucose Intolerance 5. Hypertension 6. Proinflammatory Cytokines 7. Adiponectin Metabolic Syndrome Visceral adiposity Insulin Resistance Cardiovascular disease Dyslipidemia Type 2 Diabetes Hypertension Stress 13
- 14. TNF, Adipokines NO production Pathophysiology:The role of abdominal obesity 14
- 15. Inhibit Protein kinase inMs • Insulin inhibitory lipolys Action • Protein kinase in Liver expression of ß3 – adrenergic receptors Randle’s Cycle Inhibit glycolysis, increase lipolysis & Insulin resistance Pathophysiology: The role of abdominal obesity 15 • Lipotoxic to B-cell • Compensatory hyperinsulinemic state fail
- 16. Pathophysiology- Neurohormonal activation expressionof ß3 – adrenergic receptors Inhibit glycolysis & Insulin resistance anti-inflammatory antiatherogenic, lipogenesis And HTN Hypothalamus, Leptin resistance NADP oxidase ACE 16
- 17. Pathophysiology- Inflammation expression ofß3 – adrenergic receptors 17 CRP Prothrombin Adhesion to endothelium Local RAS
- 18. Pathophysiology- Insulin Resistance Fastinghyperinsulinemia Insulin resistance Lipolysis by LPL Toxic injury to pancreatic islets Insulin resistance Type 2 DM Impaired insulin mediated glucose uptake Hyperglycemia Abundance of FFA’s 18
- 19. Pathophysiology- Insulin Resistance expressionof ß3 – adrenergic receptors Inhibit glycolysis & Insulin resistance anti-inflammatory antiatherogenic And HTN hypothalamus NADP oxidase ACE • postprandial hyperinsulinemia • fasting hyperinsulinemia • fasting hyperglycemia • IR…. FFA…IR 19
- 20. Pathophysiology- Insulin Resistance 20 Hyperlipidemia Inflamation Oxidativestress Insulin Receptor
- 21. The inflammatory componentof the metabolic syndrome • Vascular dysfunction • Endothelial dysfunction • Microalbuminuria • Proinflammatory state • Elevated hsCRP • Elevated inflammatory cytokines (TNF-α, IL-6) • Decreased adiponectin levels • Prothrombotic state • Increased antifibrinolytic factors (PAI-1) • Increased fibrinogen 21
- 22. CLINICAL FEATURES 1. Symptomsand Signs: • The metabolic syndrome typically is not associated with symptoms. • On physical examination, waist circumference- expanded and BP elevated. 2. Associated Diseases/increases risk of: 22
- 23.
- 24. DIAGNOSIS • Purpose: • Reducethe multiple risk factors • Lifestyle modification • History/examination • Bedside and laboratory test • fasting lipids and glucose • biomarkers associated with insulin resistance • ApoB, hsCRP, fibrinogen, urinary microalbumin, and liver function. • sleep study 24
- 25. Therapeutic Goals forManagement LIFESTYLE Diet Physical Activity Behavior Modification Obesity Drugs: • LDL cholesterol • Triglycerides • HDL cholesterol • Blood pressure • Impaired fasting glucose • Insulin resistance 25
- 26. Applied aspects • Insulinresistance • Thiazolidinediones (rosiglitazone, insulin sensitizing drug) • Leptin resistance • Congenital leptin deficiency • Lifestyle disorders 26
- 27. Thiazolidinediones Adipose tissue MuscleLiver Decreased FFA and TNFa release Decreased tissue triglycerides Increased adiponectin Decreased glucose output Increased glucose utilization b-cell Increased insulin secretion Vascular Increased endothelial function PPARg Adapted from Goldstein BJ. Am J Cardiol. Suppl 2002. Applied aspects Effects of Thiazolidinediones Mediated via Adipose Tissue 27
- 28. Recent advances • Newgeneration of PPAR agonists, • Interact with both PPARα and γ-receptors, thereby combining lipid and glycaemic effects. • Protein tyrosine phosphatase 1B inhibitors (PTP1B) • Act as a negative regulator of insulin and leptin receptor signalling pathways. • Leptin receptor antagonists and offer potential as future therapies 28
- 29. Summary & Conclusions •Global epidemic • Variations exist in the diagnostic criteria and definition • The concept of metabolic syndrome • Based on visceral fat accumulation & Insulin resistance • Major target for the prevention of cardiovascular disease • Lifestyle modification 29
- 30.
- 31.
- 32. Takeaway message • Hiddenvolcano • Screening >3 yrs • Evaluation ≥25 yrs • We should not wait till these killers develop Thank You 32
- 33. "The doctor ofthe future will give no medicine, but will interest his patients in the care of the human body, in diet, and in the cause and prevention of disease." .... Thomas Edison So, what can you do? The Lifestyle Disease 33