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Metabolic Syndrome Symposium Dar Al-Kalima Health and Wellness Center Bethlehem, Palestine Oct. 2005 Metabolic Syndrome: • • • • What is it? Is it important? How common is it? What should be done about it? Metabolic Syndrome Concept Not New: • 1923 - Kylin first to describe the clustering of hypertension, hyperglycemia, hyperuricemia • 1936 - Himsworth first reported Insulin insensitivity in diabetics • 1965 - Yalow and Berson developed insulin assay and correlated insulin levels & glucose lowering effects in resistant and non-resistant individuals History (cont.) • 1988 - Reaven in his Banting lecture at the ADA meeting coined the term Syndrome X and brought into focus the clustering of features of Metabolic Syndrome • Reaven now prefers the name, InsulinResistance Syndrome - feels insulin resistance is the common denominator for Metabolic Syndrome • Literature now extensive Other Names Used: • • • • • • • • Syndrome X Cardiometabolic Syndrome Cardiovascular Dysmetabolic Syndrome Insulin-Resistance Syndrome Metabolic Syndrome Beer Belly Syndrome Reaven’s Syndrome etc. Clustering of Components: • • • • • • Hypertension Hypertriglyceridemia Low HDL-cholesterol Obesity (central) Impaired Glucose Handling Microalbuninuria (WHO) Is it a Syndrome? • The Metabolic Syndrome: Time for a Critical Appraisal. – Joint Statement from the American Diabetes Association and the European Association for the Study of Diabetes – Kahn, R, et al. Diabetes Care 2005;28:22892304 Is it a Syndrome? • “…too much clinically important information is missing to warrant its designations as a syndrome.” • “Until much needed research is completed, clinicians should evaluate and treat all CVD risk factors without regard to whether a patient meets the criteria for diagnosis of the ‘metabolic syndrome’.” Criteria for diagnosis: • World Health Organization • International Diabetes Federation (IDF) European Association for the Study of Diabetes (EASD) • National Cholesterol Education Project, Adult Treatment Panel (NCEP-ATP III) • Others Hypertension: • IDF: – BP >130/85 or on Rx for previously Dxed hypertension • WHO: – BP >140/90 • NCEP ATP III: – BP >130/80 Obesity: • IDF: – Central obesity - waist circumference >94 cm for Europid men, >80 Europid women with ethnicity specific values for other groups • WHO: – Waist-hip ratio >0.9 - men or >0.85 - women • ATP III: – Waist circumference >40 in. - men, 35 in. women Glucose Abnormalities: • IDF: – FPG >100 mg/dL (5.6 mmol.L) or previously diagnosed type 2 diabetes • WHO: – Presence of diabetes, IGT, IFG, insulin resistance • ATP III: – FBS >110 mg%, <126 mg% (ADA: FBS >100) Dyslipidemia: • IDF: – Triglycerides - >150mg/dL (1.7 mmol/L) – HDL - <40 mg/dL (men), <50 mg/dL (women) • WHO: – Triglycerides - >150 mg/dL (1.7 mmol/L) – HDL - <35 mg/dL (men), >39 mg/dL) women • ATP III: – Same as IDF Necessary Criteria to Make Diagnosis: • IDF: – Require central obesity plus two of the other abnormalities • WHO: – Also requires microalbuminuria - Albumen/ creatinine ratio >30 mg/gm creatinine • ATP III: – Require three or more of the five criteria Linked Metabolic Abnormalities: • • • • • • • • Impaired glucose handling/insulin resistance Atherogenic dyslipidemia Endothelial dysfunction Prothrombotic state Hemodynamic changes Proinflammatory state Excess ovarian testosterone production Sleep-disordered breathing Resulting Clinical Conditions: • • • • • • • Type 2 diabetes Essential hypertension Polycystic ovary syndrome (PCOS) Nonalcoholic fatty liver disease Sleep apnea Cardiovascular Disease (MI, PVD, Stroke) Cancer (Breast, Prostate, Colorectal, Liver) Prevalence of Metabolic Abnormalities: • Global - approx. 314 million people with impaired glucose metabolism (500 million by 2025) • Palestine: (Hanan F. Abdul-Rahim, MSC) – – – – – HTN - 25.4%(R) vs 21.5% (U) Diabetes - 9.8%(R) vs 12%(U) IGT -8.6%(R) vs 5.9%(U) (17% of both groups had either DM or IGT!!) Hypertriglyceridemia - 22.6%(R) vs 34.8%(U) Prevalence - Palestine: (cont.) • Low HDL - 28.3%(R) vs 61.2% (U) • Overall Obesity - 28.2%(R) vs 41.5%(U) • Central Obesity - 65.7%(R) vs 39.0% (U) • Clustering of components with and without diabetes were similar in both populations. • Individuals with DM or IGT - 73.4% also had two additional components of Met. Syn. Prevalence in U.S.: • Varies with ethnicity: – Native Americans with diabetes - 55.2% – Metabolic syndrome more prevalent in Mexican/Americans and African Americans than non-Hispanic caucasians (ATP III) – Prevalence increasing in juveniles as well as adults due to overnutrition and sedentary lifestyles, smoking • Prevalence increases with aging Insulin Resistance: • Etiology is polygenic and environmental (overnutrition, sedentary life-style) • Sensitivity to insulin varies widely in the general population • Insulin-mediated glucose uptake by cells is compromised • As beta cells fail and insulin is insufficient, hyperglycemia occurs Insulin Resistance: • Hyperinsulinemic individuals are at risk for developing diabetes, hyperlipidemia, HTN, & ultimately cardiovascular disease • Patients with Metabolic Syndrome are 3.5 times as likely to die from CVD as normal people Multiple Risk Factor Management • • • • • • Obesity Glucose Intolerance Insulin Resistance Lipid Disorders Hypertension Goals: Minimize Risk of Type 2 Diabetes and Cardiovascular Disease Diabetes Control - How Important? • For every 1% rise in Hgb A1c there is an 18% rise in risk of cardiovascular events & a 28% increase in peripheral arterial disease • Evidence is accumulating to show that tight blood sugar control in both Type 1 and Type 2 diabetes reduces risk of CVD • Goals: FSBS - premeal 90-130, postmeal <180. Hgb A1c <7% BP Control - How Important? • MRFIT and Framingham Heart Studies: – Conclusively proved the increased risk of CVD with long-term sustained hypertension – Demonstrated a 10 year risk of cardiovascular disease in treated patients vs non-treated patients to be 0.40. – 40% reduction in stroke with control of HTN • Precedes literature on Metabolic Syndrome • Goal: <130/80 Lipid Control - How Important? • Multiple major studies show 24 - 37% reductions in cardiovascular disease risk with use of statins and fibrates in the control of hyperlipidemia. • Goals: LDL <70 mg% (<2.6 mmol/l) • Triglycerides <150 mg% (<1.7 mmol/l) • HDL >40 mg% (>1.1 mmol/l) Medications: • Hypertension: – ACE inhibitors, ARBs – Others - thiazides, calcium channel blockers, beta blockers, alpha blockers • Hyperlipidemia: – Statins, Fibrates, Niacin • Platelet inhibitors: – ASA, clopidogrel Insulin Resistance/Diabetes: • Insulin Sensitizers: – Biguanides - metformin – PPAR α, γ & δ agonists - Glitazones, Glitazars – Can be used in combination • Insulin Secretagogues: – Sulfonylureas - glipizide, glyburide, glimeparide, glibenclamide – Meglitinides - repaglanide, netiglamide Insulin • Insulin Analogues: – Lys-pro/Aspart/glulysine used with meals – Glargine as basal insulin • Continuous Subcutaneous Insulin Infusion (CSII) • NPH/Regular, NPH/logs - Mixed or in fixed combinations (70/30, 75/25, 50/50) • Insulin combined with oral agents New Pharmacologic Agents: • Incretin Mimetics: – GLP-1 agonist - exenatide • Dual PPAR Dual Agonists: – Glitazars • CB1 Endocannabinoid Receptor (Appetite) Antagonist: – Rimonabant Antihypertensive Medications: • Angiotensin-converting Enzyme Inhibitors (ACEI) • Angiotensin II Receptor (ARB) Blockers • Combination with Thiazides, Calcium Channel Blockers, Cardioselective Beta Blockers • Target BP: <130/80 Life-Style Modification: Is it Important? • Exercise – Improves CV fitness, weight control, sensitivity to insulin, reduces incidence of diabetes • Weight loss – Improves lipids, insulin sensitivity, BP levels, reduces incidence of diabetes • Goals: Brisk walking - 30 min./day • 10% reduction in body wt. Smoking Cessation/Avoidance: • A risk factor for development in children and adults • Both passive and active exposure harmful • A major risk factor for: – – – – insulin resistance and metabolic syndrome macrovascular disease (PVD, MI, Stroke) microvascular complications of diabetes pulmonary disease, etc. Screening/Public Health Approach • Public Education • Screening for at risk individuals: – – – – – – Blood Sugar/Hgb A1c Lipids Blood pressure Tobacco use Body habitus Family history