Metabolic Syndrome

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Signs and Symptoms of Metabolic syndrome: 5

1. central obesity (increased abdominal adipose tissue (apple shape) 2. Hyperglycemia (imparied glucose tolerance ) > diabetes mellitus 3. Dyslipidemia (increased triglycerides) -> arterial plaque buildup 4. Dyslipidemia (decreased HDL- cholesterol) -> arterial plaque buildup 5. Hypertensinon (increased blood pressure) 3 of any 5

Catabolism dominates in the fasted state: (4 major adaptations)

1. proteolysis: mobilizes amino acids in skeletal muscle 2. gluconeogenesis: in liver and kidney cells 3. Triacylglycerol lipolysis: in adipose tissue 4. Beta oxidation and ketogenesis: in liver cells

Lifetime Probability of developing metabolic syndrome: Men and Women

1:3

Risk Factors for Metabolic Syndrome: Vascular diseases

3 - fold higher risk for atherosclerosis and cardiovascular disease

Risk Factors for Metabolic Syndrome: Kidney Disease

3 - fold higher risk for chronic kidney disease

Risk Factors for Metabolic Syndrome: Diabetes Mellitus

5- fold higher risk for type 2 diabetes mellitus

Effects of physical activity

Increases insulin sensitivity and glucose transport improves cardiovascular risk - decreases blood pressure - decreases triglycerides - increases good HDL cholesterol - decreases bad LDL cholesterol improves weight management

Treatment for metabolic Syndrome: Primary intervention

Lifestyle changes Quit smoking weight reduction (<25 BMI) - healthy diet (low in sugar and fat) to lower caloric intake - increase physical activity Beneficial effects on weight, lipid profile, insulin sensitivity, and blood pressure

Cytokine: Adipocnectin - adipocytes

anti- atherogenic: decrease foam cell formation decrease vascular remodeling Anti- diabetic: increased insulin sensitivity decreased hepatic glucose output decreased in central obesity

What is the best predictor of adverse lipid proflies

central obesity

Fibrates

decrease Fatty acids and triglycerides in circulation increase HDL Cholesterol

antihypertensives

decrease blood pressure

Statins

decreases LDL cholesterol inhibit HMG- CoA reductase

Cytokine: Interleukin 6 (IL-6) - macrophate

pro-atherogenic: increases vascular inflammation Pro - diabetic: decreases insulin signalling increases in central obesity

Population attributable risk (PAR)

the proportion of heart attacks in the total population attributable to a specific risk factor

Thiazolidinediones (TZDs)

activate PPAR gamma decrease hyperglycemia

Risk Factors for Metabolic Syndrome - 6

1. Central obesity (BMI> 30) 2. Insulin resistance 3. Aging 4. Genetic predisposition 5. Hormonal Changes 6. Lack of exercise

Prevalence of Metabolic Syndrome in the US (ethnicity) : Women

Hispanic > African American > White> Other

Prevalence of Metabolic Syndrome in the US (ethnicity) : Men

Hispanic > White > Other > African American

Risk Factors for Metabolic Syndrome: Other Disorders

Increased risk for non alcoholic fatty liver disease increased risk for reproductive disorders (PCOS)

Cytokine: Tumor Necrosis Factor a (TNF-a) - Macrophage

Pro-atherogenic - increases vascular remodeling Pro - diabetic - decreases insulin sensitivity in adipocytes increased in central obesity

Cytokine: Plasminogen activator inhibitor 1 (Pal-1) - adipcytes

Pro-atherogenic: increased thrombotic (blood clot) risk at sites of atherosclerosis increased in central obesity

Risk Factors for Metabolic Syndrome: Metabolic Syndrome itself is a Risk Factor: 4

Vascular disease Diabetes Mellitus Kidney disease Other disorders

glipizide

insulin sensitizer decreases hyperglycemia

Treatment for metabolic Syndrome: Secondary intervention

management of dyslipidemia, hyperglycemia, and hypertension (blood pressure) Aspirin for cardiovascular disease prevention by reducing thrombotic events (blood clots)

What are the best predictors of cardiovascular disease and heart attack

metabolic syndrome risk factors - Dyslipiedemia, decreased HDL (49) Central Obesity (20) Hypertension (18) Diabetes (10)

Metformin

suppresses hepatic glucose production and fatty acid synthesis Decreaes hyperglycemia


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