1 / 62

METABOLIC SYNDROME: CURRENT CONCEPTS Josephine Carlos-Raboca, MD, FPCP, FPSEM

METABOLIC SYNDROME: CURRENT CONCEPTS Josephine Carlos-Raboca, MD, FPCP, FPSEM Chief, Section of Endocrinology, Diabetes and Metabolism. OUTLINE. Definition of Metabolic Syndrome Clinical Significance of Metabolic Syndrome What Causes Metabolic Syndrome

dinh
Download Presentation

METABOLIC SYNDROME: CURRENT CONCEPTS Josephine Carlos-Raboca, MD, FPCP, FPSEM

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. METABOLIC SYNDROME: CURRENT CONCEPTS Josephine Carlos-Raboca, MD, FPCP, FPSEM Chief, Section of Endocrinology, Diabetes and Metabolism

  2. OUTLINE • Definition of Metabolic Syndrome • Clinical Significance of Metabolic Syndrome • What Causes Metabolic Syndrome • Link up between Obesity, Insulin Resistance and Metabolic Syndrome • Principles in Management of Metabolic Syndrome

  3. Metabolic Syndrome • A constellation of major risk factors, life-habit risk factors: • Abdominal obesity • Atherogenic dyslipidemia • Elevated TG • Small, dense LDL particles • Low HDL-C • Elevated blood pressure • Insulin resistance • Prothrombotic and proinflammatory states Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497.

  4. WHO definition of ‘Metabolic Syndrome’ AT LEAST ONE OF: • glucose intolerance • IGT • type 2 diabetes • insulin resistance* AT LEAST TWO OF: • impaired glucose regulation or diabetes • insulin resistance* •  arterial pressure  140/90 mmHg •  plasma triglycerides  1.7 mmol/l or 150 mg/dl and/or  HDL cholesterol< 0.9 mmol/l or 35 mg/dl for men; < 1.0 mmol/l or 39 mg/dl for women • central obesitywaist:hip ratio > 0.90 for men, > 0.85 for women; and/or BMI > 30 kg/m2 • microalbuminuria urinary albumin excretion rate  20 g/min or albumin to creatinine ratio  30 mg/g + * Insulin resistance defined under hyperinsulinemic, euglycemic conditions as glucose uptake below the lowest quartile for the background population under investigation World Health Organization. Definition, diagnosis and classification of diabetes mellitus and its complications. Part I: Diagnosis and classification of diabetes mellitus. WHO Department of Noncommunicable Disease Surveillance; 1999.

  5. 2005 Revised ATP III Clinical Screening Criteria to Identify Metabolic Syndrome (AHA and NHLBI)

  6. Diagnosis of The Metabolic SyndromeIDF CRITERIA (2005) • Central obesity (defined as waist circumference 94 cm for Europid men and 80 cm for Europid women, with ethnicity specific values for other groups) • Plus any two of the following four factors • TG 150 mg/dl (1.7 mmol/l), or specific treatment for this lipid abnormality • HDL <40 mg/l (1.03 mmol/l) in males and <50 mg/l (1.29 mmol/l) in females, or specific treatment for this lipid abnormality • Systolic BP 130 or diastolic BP 85 mmHg, or treatment of previously diagnosed hypertension • Fasting plasma glucose 100 mg/dl (5.6 mmol/l), or previously diagnosed type 2 diabetes. If above 5.6 mmol/l or 100 mg/dl, OGTT is strongly recommended but is not necessary to define presence of the syndrome

  7. Diagnosis of The Metabolic SyndromeIDF CRITERIA (2005) Ethnic-specific cut-points for waist circumference

  8. Diagnosis of The Metabolic SyndromeIDF CRITERIA (2005) Ethnic-specific cut-points for waist circumference

  9. A Major Health Issue WorldwidePrevalence of the metabolic syndrome (ATP III) *Obesity criteria adjusted to waist circumference appropriate for an Indian population

  10. Clinical Significance of Metabolic Syndrome

  11. Metabolic syndrome predicts future CHD and DM Metabolic Syndrome High LDL-C T2DM Coronary Heart Disease

  12. Metabolic Syndrome and Risk of CV Events Whatever The Definition, The Metabolic Syndrome Increases 1.5 to 2-fold The Risk of CV Events Dekker JM, et al. (Hoorn study). Circulation 2005;112:666-673.

  13. 3.7 Fold Increase CHD Risk with 4-5 Features of the Metabolic Syndrome CHD Death or Non-fatal MI Sattar et a Circ 2003;108:414-419l

  14. Diabetes and Metabolic Syndrome Worsen Long-term Prognosis in Patients with Acute Myocardial Infarction G Levantesi G, et al. (GISSI-Prevenzione). J Am Coll Cardiol 2005;46:277-283.

  15. 24.5 Fold Increase Risk of New Onset Diabetes with 4-5 Features of the Metabolic Syndrome Onset of new DM Sattar et a Circ 2003;108:414-419l

  16. Other Associated Disorders • Obstructive Sleep Apnea • Fatty Liver (Non Alcoholic Steatorrheic Hepatitis) • Arthritis • Polycystic Ovarian Syndrome • Malignancy

  17. What is the root cause of Metabolic Syndrome? Insulin Resistance? Obesity? Inflammation?

  18. The Metabolic Syndrome: a network of atherogenic factors Genetic factors Environmental Factors (Obesity, Physical Inactivity) Hyperglycemia/IGT Dyslipidemia Hypertension Endothelial dysfunction/ Microalbuminuria Hypofibrinolysis Inflammation Insulin Resistance Atherosclerosis McFarlane S, et al. J Clin Endocrinol Metab 2001; 86:713–718.

  19. Link between Insulin Resistance and Metabolic Syndrome

  20. Endothelial dysfunction Carbohydrate Excessive fatty acid release Defective insulin secretion Excess glucose production Reduced glucose uptake Resistance to the action of insulin Insulin resistance – a reduced response of target tissues to circulating insulin Glucose (G) G I I G Insulin (I) G G I G I G I G I G G I I G G I G

  21. Indicators of Insulin Resistance • HOMA • Hyperinsulinemia • Triglyceride/HDL >4

  22. Insulin Resistance Syndrome Central obesity Endothelial dysfunction/ microalbuminuria Hyperglycemia Insulin resistance Dyslipidemia Hypertension Hypofibrinolysis Inflammation Cardiovascular disease Festa A et al. Circulation 2000; 102:42–47; Reaven GM et al. Annu Rev Med 1993; 44:121–131.

  23. Prevalence of insulin resistance correlates with increasing number of metabolic disorders 100 80 60 Prevalence of HOMA-estimated insulin resistance (%) 40 20 0 0 1 2 3 4 Number of metabolic disorders n = 888 Metabolic disorders: glucose intolerance, dyslipidemia, hyperuricemia and/or hypertension. P < 0.001 for differences between all categories. Bonora E, et al. Diabetes 1998; 47:1643.

  24. Link between Obesity and Metabolic Syndrome • Fat accumulation leads to systemic oxidative stress • Increase ROS (eg H2O2) -increase NADPH oxidase activity and decreased antioxidant enzymes – leads to dysregulated adipocytokine production - insulin resistance - increase MCP -1 – HPN and atherosclerosis

  25. Insulin resistant adipocytes secrete multiple signaling molecules linked with inflammation & insulin resistance Free fatty acids  TNF a  Leptin  Resistin  Adiponectin  Angiotensin II  PAI-1

  26. Adipokines Mediates IR and Inflammation Adiponectin,  TNF,  Leptin, PAI-1,  IL-6, Angiotensinogen Insulin Resistance  Insulin Sensitivity  Vascular Infllammation Endothelial Dysfunction

  27. How Does Abdominal Obesity Cause Insulin Resistance Reduced Physical Activity Excessive food intake Inflammation insulin receptor Substrate (IRS-1 & IRS-2)  IL-6 Genetic factors  TNF-  various cytokines adiponectin  ABDOMINAL OBESITY Insulin resistance  leptin Hormones  blood FFA

  28. Liver FFA CE (HL)  TG Apo B (CETP) HD2 VLDL HDL3 Insulin Resistant Abdominal Adipocytes TG Apo A-1 (CETP) CE TG Kidney LDL • small, Dense LDL LDL ( HL) Insulin Resistance of Abdominal Adipose Tissue and Atherogenic Dyslipidaemia

  29. Visceral Fat Associates with Atherogenic Dyslipidaemia Adapted from Pouliot MC, et al. Diabetes 1992;41:826-834.

  30. Low HDL-C Predicts CHD Risk Low HDL-C is an independent predictor of CHD riskeven when LDL-C is low Castelli WP. Can J Cardiol. 1998;4 (suppl A):5A-10A.

  31. Patients with Elevated Triglycerides are at IncreasedRisk for CHD High TG associates with higher relative risk for CHD in the Framingham Heart Study Castelli WP. Can J Cardiol. 1998;4 (suppl A):5A-10A.

  32. Small, Dense, LDL Particles were an IndependentRisk Factor for CAD in Quebec Cardiovascular Study St Pierre, et al. Circulation. 2001:104:2295.

  33. Obesity Is An Inflammatory Stimulus • Metabolic syndrome is a proinflammatory, proatherogenic condition • Many adipose tissue products can cause insulin resistance and inflammation: • Cytokines (e.g., TNF-a, IL-6) • Chemokines • Growth factors • Procoagulants (e.g., PAI-1) • Free fatty acids • Resistin • Adiponectin • Nitric oxide synthase

  34. Atherosclerosis Is An Inflammatory Disease • Initial step of atherosclerosis: leukocyte recruitment by the dysfunctional endothelium, facilitated by chemo-attractants and adhesion molecules (VCAM-1, ICAM-1) • In the intima, maturation of the mononuclear phagocyte towards the foam cell (capture of modified lipoproteins) • Activated foam cells • express the procoagulant tissue factor • generate reactive oxygen species and pro-inflammatory cytokines (CRP, IL-6) • can also be the source of enzymes that alter the metabolism of the extracellular matrix • Death of the mononuclear phagocyte by either oncosis or apoptosis leads to formation of the lipid core of the atherosclerotic plaque

  35. Atherosclerosis Is An Inflammatory Disease • The endothelium and smooth muscle vascular cells can themselves elaborate pro-inflammatory cytokines. • In the initial phase of inflammation, elaboration of pro-inflammatory cytokines and the cross talk between leukocytes and intrinsic vascular wall cells play a key role in the initiation of the progression phase.

  36. Atherosclerosis Is An Inflammatory Disease • Alterations in the metabolism of the extracellular matrix under the plaque arterial remodelling • Suppression of new collagen synthesis by smooth muscle cells • Overproduction of collagen-degrading proteinases that attack the collagen within the fibrous cap • Inflammatory mediators tightly control the biosynthesis of tissue factor (a procoagulant) • Weakening of the fibrous cap thrombosis of a disrupted atheroma

  37. C-Reactive Protein andMetabolic Syndrome Ridker et al. Circulation. 2003;107:391.

  38. High CRP Levels Predict CVD in Patients with and without Metabolic Disorders Malik S, et al. (NHANES 1999-2000). Diabetes Care. 2005;28:690-93.

  39. Adiponectin Levels are Significantly Lower in Hypertensive Subjects Iwashima Y, et al. Hypertension 2004;43:1318-1323.

  40. ROS Excess FFA are linked to both Insulin Resistance and Inflammation FFA FA CoA DAG IkB P --Ser—IRS1 PKC NFkB Inflammation Insulin Resistance Inoguchi et al. Diabetes 2000;49:1939-45. Yu et al. Diabetologia 2001;44:614-20; Lu et al. Circ.Res. 1996;79:611-8.

  41. Elevated circulating FFA is a central factor in the development of type 2 diabetes Insulin resistance High insulin demand and insulin resistance in pancreas Decreased glucose uptake into muscle and adipose tissue and raised hepatic glucose output Increased lipolysis lipotoxicity glucotoxicity Elevated circulating FFA Hyperglycemia -cell dysfunction Arner P. Diabetes Obes Met 2001;3 (Suppl.1); S11–S19.

  42. Obesity, Type 2 Diabetes, and Metabolic Syndrome: 3 Interrelated Epidemics Overweight/Obesity: a worldwide epidemic • >1 billion adults worldwide were: • - Overweight in 2002 1-BMI>25 kg/m2 • At least 300 million are clinically obese 2 • - BMI>30 kg/m2 1- World Health Organization. Global strategy on diet, physical activity and health, 2003. Available at: http://www.who.int/hpr/NPH/docs/gs_obesity.pdf. Accessed November 11, 2003. 2- International Obesity Task Force. Available at: http://www.iotf.org. Accessed November 13, 2003.

  43. The Metabolic Syndrome Is A Metabolic Time Bomb • With the elevated risk of diabetes andcardiovascular disease from the metabolic syndrome, there is an urgent need for strategies to defuse this metabolic time bomb

  44. Management of Metabolic Syndrome

  45. What to do About the Metabolic Syndrome? • Intervening in the Metabolic Syndrome: • Cardiovascular Risk Assessment • Metabolic Syndrome • Traditional Risk Factors • B. Lifestyle Modification • C. Drug Treatment

  46. First Step: Assessment of Global Cardiovascular Risk • Risk engines incorporate the major cardiovascular risk factors into a summary 10-year CHD risk score • Framingham: age, sex, smoking, total cholesterol, HDL-C, systolic blood pressure or treated hypertension • PROCAM: age, smoking, LDL-C, HDL-C, triglycerides, SBP, fasting blood glucose, diabetes, treated hypertension, family history of CHD • UKPDS risk engine: estimation of cardiovascular risk in patients with type 2 diabetes and no previous MI

  47. Therapeutic Objectives To reduce underlying causes: • Overweight and obesity • Physical inactivity To treat associated lipid and non-lipid risk factors: • Hypertension • Prothrombotic state • Atherogenic dyslipidaemia • Insulin Resistance or Glucose Intolerance

  48. Lifestyle Therapies: First-Line Interventions to Reduce Metabolic Risk Factors • The major lifestyle interventions include: • Weight loss in overweight or obese subjects • Increased physical activity • Modification of an atherogenic diet • These changes will produce a reduction in all of the metabolic risk factors simultaneously • In the long run, the greatest benefit for those with the metabolic syndrome will be derived from effective lifestyle intervention

  49. Weight Reduction or Maintenance • Weight reduction through caloric restriction: • Caloric intake should be reduced by 500-1000 calories per day to produce a weight loss of 0.5-1.0 kg per week • The goal is to reduce bodyweight by about 7-10% over 6-12 months • Weight maintenance can be achieved throughlong-term lifestyle changes

  50. Dietary Changes • Caloric restriction must be combined with a set of dietary principles: • Saturated fat: 7% of total calories • Reduced trans fat • Dietary cholesterol: <200 mg daily • Total fat: 25-35% of total calories • Reduced consumption of simple sugars • Increased intakes of fruits, vegetables, and whole grains The relative amounts of carbohydrate and unsaturated fats is more controversial

More Related