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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 syndrome symposium l.jpg

Metabolic SyndromeSymposium

Dar Al-Kalima Health and Wellness Center

Bethlehem, Palestine

Oct. 2005


Metabolic syndrome l.jpg
Metabolic Syndrome:

  • What is it?

  • Is it important?

  • How common is it?

  • What should be done about it?


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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


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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


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Other Names Used:

  • Syndrome X

  • Cardiometabolic Syndrome

  • Cardiovascular Dysmetabolic Syndrome

  • Insulin-Resistance Syndrome

  • Metabolic Syndrome

  • Beer Belly Syndrome

  • Reaven’s Syndrome

  • etc.


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Clustering of Components:

  • Hypertension

  • Hypertriglyceridemia

  • Low HDL-cholesterol

  • Obesity (central)

  • Impaired Glucose Handling

  • Microalbuninuria (WHO)


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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


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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’.”


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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


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Hypertension:

  • IDF:

    • BP >130/85 or on Rx for previously Dxed hypertension

  • WHO:

    • BP >140/90

  • NCEP ATP III:

    • BP >130/80


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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


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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)


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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


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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


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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


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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)


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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)


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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.


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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


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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


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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


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Multiple Risk Factor Management

  • Obesity

  • Glucose Intolerance

  • Insulin Resistance

  • Lipid Disorders

  • Hypertension

  • Goals: Minimize Risk of Type 2 Diabetes and Cardiovascular Disease


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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%


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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


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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)


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Medications:

  • Hypertension:

    • ACE inhibitors, ARBs

    • Others - thiazides, calcium channel blockers, beta blockers, alpha blockers

  • Hyperlipidemia:

    • Statins, Fibrates, Niacin

  • Platelet inhibitors:

    • ASA, clopidogrel


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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


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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


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New Pharmacologic Agents:

  • Incretin Mimetics:

    • GLP-1 agonist - exenatide

  • Dual PPAR Dual Agonists:

    • Glitazars

  • CB1 Endocannabinoid Receptor (Appetite) Antagonist:

    • Rimonabant


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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


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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.


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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.


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Screening/Public Health Approach

  • Public Education

  • Screening for at risk individuals:

    • Blood Sugar/Hgb A1c

    • Lipids

    • Blood pressure

    • Tobacco use

    • Body habitus

    • Family history


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