Linked Metabolic Abnormalities Impaired glucose handling insulin resistance

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)

Multiple Risk Factor Management • Obesity • Glucose Intolerance • Insulin Resistance • Lipid Disorders • Hypertension • Goals: Minimize Risk of Type 2 Diabetes and Cardiovascular Disease

Glucose Abnormalities: • IDF: • • – FPG >100 mg/d. L (5. 6 mmol. L) or previously diagnosed type 2 diabetes WHO: – Presence of diabetes, IGT, IFG, insulin resistance ATP III: – FBS >110 mg/d. L, <126 mg/d. L (6. 1 -7. 1 mmol/L ) – (ADA: FBS >100 mg/d. L [ 5. 6 mmol/L ])

Hypertension: • IDF: • • – BP >130/85 or on Rx for previously diagnosed hypertension WHO: – BP >140/90 NCEP ATP III: – BP >130/80

Dyslipidemia: • IDF: • • – Triglycerides - >150 mg/d. L (1. 7 mmol /L) – HDL - <40 mg/d. L (men), <50 mg/d. L (women) WHO: – Triglycerides - >150 mg/d. L (1. 7 mmol/L) – HDL - <35 mg/d. L (men), >39 mg/d. L) women ATP III: – Same as IDF

Screening/Public Health Approach • • Public Education Screening for at risk individuals: – Blood Sugar/ Hb. A 1 c – Lipids – Blood pressure – Tobacco use – Body habitus – Family history

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.

Diabetes Control - How Important? • • • For every 1% rise in Hb A 1 c 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: Goals • FBS - premeal <110, • postmeal <180. • Hb. A 1 c <7%

Overcome Insulin Resistance/ Diabetes: • Insulin Sensitizers: – Biguanides - metformin – PPAR α, γ & δ agonists – Glitazones, Gltazars Rosiglitazon, Pioglitazon – Can be used in combination • Insulin Secretagogues: – Sulfonylurea - glipizide, glyburide, glimeparide, glibenclamide – Meglitinides - repaglanide, netiglamide

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: BP. <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 <100 mg/d. L (<3. 0 mmol /l) (high risk <70 mg/d. L- <2. 6 mmol/L) TG <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 – Central acting Alfa agonist : Moxolidin Dylipidemia: – Statins, Fibrates, Niacin Platelet inhibitors: – ASA, clopidogrel

A Critical Look at the Metabolic Syndrome • • • Is it a Syndrome? * “…too much clinically important information is missing to warrant its designations as a syndrome. ” Unclear pathogenesis, Insulin resistance may not underlie all factors, & is not a consistent finding in some definitions. CVD risks associated with metabolic syndrome has not shown to be greater than the sum of it’s individual components. *ADA & EASD

A Critical Look at the Metabolic 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’. ” The advice remains to treat individual risk factors when present & to prescribe therapeutic lifestyle changes & weight management for obese patients with multiple risk factors.

Individual metabolic abnormalities among Qatari population according to gender (Musallam et al 08) Men (n = 405) Women (n=412) Variable n(%) ATP III n(%) p-Value Abdominal obesity 227(56. 0) 308(74. 8) <0. 001 Hypertension 143(35. 3) 156(37. 9) 0. 448 Diabetes 77(19. 0) 107(26. 0) 0. 017 Hypertriglyceridemia 113(27. 9) 83(20. 1) 0. 009 Low HDL 95(23. 5) 121(29. 4) 0. 055

Individual metabolic abnormalities among Qatari population according to gender No of components of ATP III Men (n = 405) Variable n(%) Women (n=412) p-Value None 88(21. 7) 74(18. 0) – One 103(25. 4) 100(24. 3) Two 125(30. 9) 111(26. 9) – Three or more 89(22. 0) 127(30. 8) – 0. 033

Multivariate logistic regression analysis of factors associated with Metabolic Syndrome according to (ATP III criteria) Age Female gender Odds ratio 95% CI p-Value 1. 07 1. 05– 1. 09 <0. 001 1. 86 1. 30– 2. 67 0. 001 Body Mass Index 1. 05 1. 02– 1. 07 <0. 001 Fam his of DM 1. 66 1. 12– 2. 44 0. 011 Smoking 3. 27 1. 63– 6. 55 0. 001

Prevalence of Me. S in different Countries Country Year Sample Prevalence (%) Arab Americans 2003 542 23 Oman 2001 1419 21 Jordan 2002 1121 36 Saudi Arabia 2004 2250 20. 8 Palestine 1998 Qatar 2007 817 27. 6 Turkey 2004 1637 33. 4* Iran ? 10368 33. 7 * Crude rates 17* Mussallam et al. Int J Food Safety and PH 2008

Prevalence of Me. S in different Countries Country Year Sample Prevalence (%) USA 2005 2002 34* Greece 2005 1419 21 South Australia 2005 4060 15. 3 S. Korea 2001 40, 698 6. 8 China 2000 2776 10. 2* Turkey 2004 1637 33. 4* Chennai India 2003 475 41* Qatar 2001 817 27. 6 * Crude rates Mussallam et al. Int J Food Safety and PH 2008