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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 :.
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Metabolic SyndromeSymposium 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, Insulin-Resistance 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;28:2289-2304
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 life-styles, 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 majorrisk factorfor: • 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