Kuliah MetS

Slide 1: 

Metabolic Syndrome MAJ(P) J. Scott Earwood Metabolic Syndrome

Metabolic syndrome : 

Metabolic syndrome is a combination of medical disorders that, when occurring together, increase the risk of developing cardiovascular disease and diabetes.

Other Names Used: : 

Other Names Used: Syndrome X Cardiometabolic Syndrome Cardiovascular Dysmetabolic Syndrome Insulin-Resistance Syndrome Metabolic Syndrome Beer Belly Syndrome Reaven’s Syndrome

Clustering of Components: : 

Clustering of Components: Hypertension Hypertriglyceridemia Low HDL-cholesterol Central obesity Impaired Glucose Handling Microalbuninuria

Risk Factor : 

Risk Factor Gelfand EV et al, 2006; Vasudevan AR et al, 2005 * working definition

Criteria for diagnosis: : 

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

International Diabetes Federation : 

International Diabetes Federation Central obesity (defined as waist circumference# with ethnicity specific values) AND any two of the following: Raised triglycerides: > 150 mg/dL (1.7 mmol/L), or specific treatment for this lipid abnormality. Reduced HDL cholesterol: < 40 mg/dL (1.03 mmol/L) in males, < 50 mg/dL (1.29 mmol/L) in females, or specific treatment for this lipid abnormality Raised blood pressure: systolic BP > 130 or diastolic BP >85 mm Hg, or treatment of previously diagnosed hypertension. Raised fasting plasma glucose :(FPG)>100 mg/dL (5.6 mmol/L), or previously diagnosed type 2 diabetes. If FPG >5.6 mmol/L or 100 mg/dL, OGTT Glucose tolerance test is strongly recommended but is not necessary to define presence of the Syndrome. # If BMI is >30 kg/m², central obesity can be assumed and waist circumference does not need to be measured

Ethnic specific values for waist circumference (IDF) : 

Ethnic specific values for waist circumference (IDF) Europids : Male ≥ 94 cm Female ≥ 80 cm South Asians : Male ≥ 90 cm Female ≥ 80 cm Chinese : Male ≥ 90 cm Female ≥ 80 cm Japanese : Male ≥ 85 cm Female ≥ 90 cm Ethnic South and Central : Use South Asian recommendations until more specific Americans : data are available (ATPIII) Sub-Saharan Africans : Use European data until more specific data are available Eastern Mediterranean and Middle East (Arab) populations : Use European data until more specific data are available

The WHO criteria (1999) : 

The WHO criteria (1999) The presence of one of: Diabetes mellitus Impaired glucose tolerance Impaired fasting glucose or Insulin resistance AND two of the following: Blood pressure: ≥ 140/90 mmHg Dyslipidemia : triglycerides (TG): ≥ 1.695 mmol/L and high-density lipoprotein cholesterol (HDL-C) ≤ 0.9 mmol/L (male), ≤ 1.0 mmol/L (female) Central obesity: waist:hip ratio > 0.90 (male); > 0.85 (female), or body mass index > 30 kg/m2 Microalbuminuria : urinary albumin excretion ratio ≥ 20 µg/min or albumin : creatinine ratio ≥ 30 mg/g

National Cholesterol Education Program Adult Treatment Panel III : 

National Cholesterol Education Program Adult Treatment Panel III NCEP requires at least three of the following: Central obesity: waist circumference : ≥ 102 cm or 40 inches (male) ≥ 88 cm or 36 inches (female) Dyslipidemia: TG ≥ 150 mg/dl Dyslipidemia: HDL-C < 40 mg/dL (male), < 50 mg/dL (female) Blood pressure ≥ 130/85 mmHg Fasting plasma glucose ≥ 110 mg/dl

AHA/ Updated NCEP : 

AHA/ Updated NCEP Elevated waist circumference: Men : > 102 cm Women : > 88 cm Elevated triglycerides: ≥ 150 mg/dL Reduced HDL (“good”) cholesterol: Men : < 40 mg/dL Women : < 50 mg/dL Elevated blood pressure: ≥ 130/85 mm Hg or use of medication for hypertension Elevated fasting glucose: ≥ 100 mg/dL or use of medication for hyperglycemia

Other Indicators of Metabolic Syndrome and CV Risk : 

Other Indicators of Metabolic Syndrome and CV Risk CRP Borderline LDL

Etiology : 

Etiology The exact mechanisms of the complex pathways of metabolic syndrome are not yet completely known. Most patients are older, obese, sedentary, and have a degree of insulin resistance The most important factors are: - weight - genetics - endocrine disorders (polycystic ovary syndrome) - aging - sedentary lifestyle (low physical activity and excess caloric intake)

Etiology : 

Etiology There is debate : whether obesity or insulin resistance is the cause of the metabolic syndrome or if they are consequences of a more far-reaching metabolic derangement. Increased markers of systemic inflammation : C-reactive protein, fibrinogen, interleukin 6 (IL–6), Tumor necrosis factor-alpha (TNFα), and others, often

Insulin Resistance: Associated Conditions : 

Insulin Resistance: Associated Conditions

Patophysiology : 

Patophysiology Development of visceral fat  adipocytes (fat cells) of the visceral fat increase plasma levels of TNF-α  alter levels of a number of other substances (e.g., adiponectin, resistin, PAI-1) TNF-α : - production of inflammatory cytokines - trigger cell signaling by interaction with a TNFα receptor that may lead to insulin resistance.

Patophysiology : 

Patophysiology An experiment with rats : were fed a diet one-third of which was sucrose has been proposed as a model for the development of metabolic syndrome. The sucrose first elevated blood levels of triglycerides, which induced visceral fat and ultimately resulted in insulin resistance. The progression from visceral fat to increased TNFα to insulin resistance has some parallels to human development of metabolic syndrome. The increase in adipose tissue also increases the number of immune cells present within, which play a role in inflammation. Chronic inflammation contribute to an increased risk of hypertension, artherosclerosis and diabetes.

Symptoms and features : 

Symptoms and features Fasting hyperglycemia— diabetes mellitus type 2 or impaired fasting glucose, impaired glucose tolerance, or insulin resistance High blood pressure Central obesity (also known as visceral, male-pattern or apple-shaped adiposity), overweight with fat deposits mainly around the waist Decreased HDL cholesterol Elevated triglycerides Associated diseases and signs are: hyperuricemia, fatty liver (especially in concurrent obesity) progressing to non-alcoholic fatty liver disease, polycystic ovarian syndrome, and acanthosis nigricans

Slide 19: 

Coagulation factors Anti-fibrinolytic factors Overeating, inactivity (acquired / genetic) Liver Muscle Predisposition to atherothrombotic vascular disease Glucose Type 2 diabetes MODERN VIEW OF INSULIN RESISTANCE Insulin resistance VLDL Courtesy of Yki-Järvinen H

Slide 20: 

Appropriate & aggressive therapy  reducing patient risk of cardiovascular disease Lifestyle measures should be the first action Pharmacotherapy should have beneficial effects on Glucose intolerance/diabetes Obesity Hypertension Dyslipidaemia Ideally, treatment should address all of the components of the syndrome and not the individual components Management of the Metabolic Syndrome

Slide 21: 

Treatment of Metabolic Syndrome: 2005