1. Dr :Reem Murad

2.  Syndrome X  Cardiometabolic Syndrome  Cardiovascular Dysmetabolic Syndrome  Insulin-Resistance Syndrome  Metabolic Syndrome  Beer Belly Syndrome  Reaven ’ s Syndrome  etc.

4.  Hypertension  Hypertriglyceridemia  Low HDL-cholesterol  Obesity (central)  Impaired Glucose Handling  Microalbuninuria (WHO)

5. The more components of the syndrome that you have, the greater the risks to your health. Signs and Symptoms

6.  Impaired glucose handling/insulin resistance  Atherogenic dyslipidemia  Endothelial dysfunction  Prothrombotic state  Hemodynamic changes  Proinflammatory state  Excess ovarian testosterone production  Sleep-disordered breathing

7.  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)

10. Lean MEJ, et al. Lancet;1998:351:853–6 IOTF, 1996 Women Men >94 increased risk >102 cm = Substantially increased risk >94 increased risk >102 cm = Substantially increased risk cm >80 increased risk >88 cm = Substantially increased risk >80 increased risk >88 cm = Substantially increased risk However, these cut points lose their reliability or predictive power in patients with BMI >35

11.  Dysfunctional adipose tissue due to combined disorders  Products of dysfunctional adipose tissue  Elevation in:  Non-esterified fatty acids  insulin resistance & dyslipidemia  Cytokines  proinflammatory state  PAI-1  prothrombotic state  Angiotensinogen  elevated blood pressure  Resistin  insulin resistance  Reduced adiponectin  insulin resistance, dyslipidemia, and proinflammatory state

14. Subccuteneous Visceral Retroperitoneal

16.  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

19. Larger, more buoyant LDL Small, dense LDL LDL= 130 mg/dL Less Atherogenic “Normal” More Atherogenic “Insulin Resistance” Cholesterol ester More Apo B Apo B

26.  Multifactor theory:  Structural and functional injury of vascular endothelium;  Response to injury of immune cells and smooth muscle cells;  The role of lipoproteins in initiation and progression of lesions;  The role of growth factors and cytokines;  The role of repeated thrombosis in lesions progression.

30.  The term atherosclerosis, which comes from the Greek words atheros (meaning “gruel” or “paste”) and sclerosis (meaning “hardness”),  contributes to more mortality and more serious morbidity than any other disorder in the western world.

31.  One of the earliest responses to elevated cholesterol levels is the attachment of monocytes to the endothelium.  The monocytes emigrate through the cell-to-cell attachments of the endothelial layer into the subendothelial spaces, where they are transformed into macrophages.  Activated macrophages release free radicals that oxidize LDL.  Oxidized LDL is not recognized at the cell receptor level and so, it can not be internalized and it longer remains into the blood stream.  Oxidized LDL is toxic to the endothelium, causing endothelial loss and exposure of the subendothelial tissue to blood components:  It has chemotactic effect on lymphocytes and monocytes;  It has chemotactic effect on smooth muscle cells from the arterial media and stimulates production of MG-CSF, cytokines, adhesion molecules in the endothelium;  It inhibits endothelium derived releasing factor (EDRF), favoring vasospasm;  It stimulates specific immune system (production of antibodies against oxidized LDL).

32.  Endothelial disruption leads to platelet adhesion and aggregation and fibrin deposition.  Platelets and activated macrophages release various factors that are thought to promote growth factors that modulate the proliferation of smooth muscle cells and deposition of extracellular matrix in the lesions: elastin, collagen, proteoglycans.  Activated macrophages also ingest oxidized LDL to become foam cells, which are present in all stages of atheroscleroticplaque formation.  Lipids released from necrotic foam cells accumulate to form the lipid core of unstable plaques.  Connective tissue synthesis determinates stiffness, calcium fixation and further ulceration of atheromatous plaque.

33.  Glycosylation is a process that affects lipoproteins, circulating proteins and proteins component of the arterial wall.  Effects:  Glycated LDL stimulates platelet aggregation and forms covalent bounds with the proteins of the arterial wall.  Glycated HDL blocks cholesterol efflux from the cells.  Collagen glycosylation increases arterial wall stiffness, activates macrophages and stimulates lipoprotein adherence.  Glycosylated proteins form circulating antigens which generates antibody and circulating immune complexes that will lead to other arterial lesions.

34.  The clinical manifestations of atherosclerosis depend on the vessels involved and the extent of vessel obstruction.  Atherosclerotic lesions produce their effects through:  narrowing of the vessel and production of ischemia;  sudden vessel obstruction caused by plaque hemorrhage or rupture;  thrombosis and formation of emboli resulting from damage to the vessel endothelium;  In larger vessels complications are thrombus formation and weakening of the vessel wall.  In medium-size arteries ischemia and infarction

35.  The term coronary heart disease (CHD) describes heart disease caused by impaired coronary blood flow.  In most cases, it is caused by atherosclerosis.  Diseases of the coronary arteries can cause:  Angina  Myocardial infarction or heart attack  Cardiac dysrhythmias  Conduction defects  Heart failure  Sudden death

36. For a healthy person, the LDL/HDL ratio is 3.5

37.  Atherosclerosis is by far the most common cause of CHD, and atherosclerotic plaque disruption the most frequent cause of myocardial infarction and sudden death.  More than 90% of persons with CHD have coronary atherosclerosis.  Most, if not all, have one or more lesions causing at least 75% reduction in cross-sectional area, the point at which augmented blood flow provided by compensatory vasodilation no longer is able to assure even moderate increases in metabolic demand.  There are two types of atherosclerotic lesions:  the fixed or stable plaque, which obstructs blood flow  commonly implicated in chronic ischemic heart disease: stable angina, variant or vasospastic angina, and silent myocardial ischemia;  the unstable or vulnerable plaque, which can rupture and cause platelet adhesion and thrombus formation  commonly implicated in unstable angina and myocardial infarction.

38.  Angiotensin-converting Enzyme Inhibitors (ACEI)  Angiotensin II Receptor (ARB) Blockers  Combination with Thiazides, Calcium Channel Blockers, Cardioselective Beta Blockers  Target BP : <130/80

39.  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

40.  Incretin Mimetics:  GLP-1 agonist - exenatide  Dual PPAR Dual Agonists:  Glitazars  CB1 Endocannabinoid Receptor (Appetite) Antagonist:  Rimonabant

41.  Obesity  Glucose Intolerance  Insulin Resistance  Lipid Disorders  Hypertension  Goals: Minimize Risk of Type 2 Diabetes and Cardiovascular Disease

42.  For every 1% rise in Hgb A1c there is an 18% rise in risk of cardiovascular events & a 28% increase in peripheral arterial disease  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%

43.  To reduce insulin resistance in overweight and obese individuals, the preferred method is an aggressive regimen of self-care strategies focusing on diet and exercise.  It is common for your doctor to routinely monitor the following to ensure that lifestyle modifications are working: o Weight o Blood glucose o Cholesterol o Blood pressure

44.  Lose weight o Losing as little as 5 to 10% of your body weight can reduce insulin levels and high blood pressure, thus reducing your risk of diabetes.  Exercise o Walking just 30 minutes a day or engaging in other aerobic activities can help prevent the serious diseases associated with MS.  Stop smoking o Smoking cigarettes increases insulin resistance and worsens health consequences associated with MS.  Eat fiber-rich foods o Whole grains, beans, fruits and vegetables are high in dietary fiber. These are important foods to eat since dietary fiber is known to lower insulin levels. Although metabolic syndrome creates a real risk for developing diabetes, stroke or heart disease, these conditions can be prevented. Insulin resistance can be controlled by the following :

45.  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.

46.  Hypertension:  ACE inhibitors, ARBs  Others - thiazides, calcium channel blockers, beta blockers, alpha blockers  Hyperlipidemia:  Statins, Fibrates, Niacin  Platelet inhibitors:  ASA, clopidogrel

47.  A risk factor  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.

48.  Commit to a healthy diet o A healthy diet includes plenty of fruits and vegetables, choosing lean cuts of white meat and fish over red meat, avoiding processed or deep-fried dinners, and eliminating table salt by experimenting with other herbs and spices.  Get moving o It is important to stay active. Get at least 30 minutes of moderately strenuous activity on most days of the week is recommended.  Schedule regular check-ups o This includes assessing blood pressure, cholesterol and blood sugar levels annually. Early detection of problems can help with formulating lifestyle modifications. Healthy lifestyle changes can prevent the onset of the syndrome.

49. HyperinsulinemiaIGTHyperinsulinemiaIGT DyslipidemiaHypertensionCoagulation abnormalityDyslipidemiaHypertensionCoagulation abnormality Insulin Resistance Type 2 Diabetes Hidden Dangers Hidden Dangers