Presentation Metabolic Syndrome

8/9/2019 Presentation Metabolic Syndrome

1/56

The Metabolic Syndrome

Dr. loay Shakerdi

Abdulhakeem Tleimat


2/56

The Metabolic Syndrome

Goals : Define the metabolic syndrome.

Determine common risk factors. Learn the etiology. Approach to a patient with metabolic syndrome

(clinical features and associated diseases)

ATPIII and IDF criteria of diagnosis. Treatment and prevention.


3/56

DEFINITION

The metabolic syndrome (syndrome X, insulin resistancesyndrome) consists of a constellation of metabolic

abnormalities that confer increased risk ofcardiovascular disease (CVD) and diabetes

mellitus(DM).


4/56

DEFINITION

The major features of the metabolic syndrome include: Central obesity. Hypertriglyceridemia. Low HDL cholesterol. Hyperglycemia. Hypertension.


5/56

EPIDEMIOLOGY

In general, the prevalence of metabolic syndromeincreases with age. The highest recorded prevalence

worldwide is in Native Americans, with nearly 60% ofwomen ages 4549 and 45% of men ages 4549meeting National Cholesterol Education Program,Adult Treatment Panel III (NCEP:ATPIII) criteria.

In France, a 3064-year-old cohort shows a


6/56

EPIDEMIOLOGY

Prevalence of the metabolic syndrome components, from NHANES III. NHANES, National

Health and Nutrition ExaminationSurvey; TG, triglyceride; HDL, high-density lipoprotein; BP,

blood pressure. (From ES Ford et al: JAMA 287:356, 2002; with permission.)


7/56

RISK FACTORS

Overweight/Obesity. Sedentary Lifestyle. Aging. Diabetes Mellitus. Coronary Heart Disease. Lipodystrophy.


8/56

RISK FACTORS

Central adiposity is a key feature of thesyndrome, reflecting the fact that the syndromes

prevalence is driven by the strong relationship betweenwaist circumference and increasing adiposity. However,

despite the importance of obesity, patients who arenormal weight may also be insulin-resistant and

have the syndrome.

Overweight/Obesity


9/56

RISK FACTORS

Compared with individuals who watched televisionor videos or used their computer 4 h daily have a twofoldincreased risk of the metabolic syndrome.

Sedentary Lifestyle


10/56

RISK FACTORS

The metabolic syndrome affects 44% of the U.S.population older than age 50.

The age dependency of the syndromes prevalence is seenin most populations around the world.

Aging


11/56

RISK FACTORS

(~75%) of patients with type 2 diabetes or impairedglucose tolerance (IGT) have the metabolic syndrome.

Diabetes Mellitus


12/56

RISK FACTORS

The approximate prevalence of the metabolic syndrome inpatients with coronary heart disease (CHD) is 50%, witha prevalence of 37% in patients with premature coronary

artery disease

Coronary heart Disease


13/56

RISK FACTORS

Both genetic (e.g., Berardinelli-Seip congenitallipodystrophy, Dunnigan familial partial lipodystrophy) andacquired (e.g., HIV-related lipodystrophy in patients

treated with highly active antiretroviral therapy) forms oflipodystrophy may give rise to severe insulin resistance

and many of the metabolic syndromescomponents.

Lipodystrophy


14/56

ETIOLOGY

Insulin Resistance. Increased Waist Circumference. Dyslipidemia. Glucose Intolerance. Hypertension. Proinflammatory Cytokines. Adiponectin.


15/56

ETIOLOGY

Pathophysiology of the metabolic syndrome.


16/56


17/56

ETIOLOGY

An early major contributor to the development of insulinresistance is an overabundance of circulating fatty acids.Fatty acids impair insulin-mediated glucose uptake andaccumulate as triglycerides in both skeletal and cardiac

muscle, whereas increased glucose production andtriglyceride accumulation are seen in liver.

Insuline Resistance


18/56

ETIOLOGY

Measuring waist circumference does not reliablydistinguish between a large waist due to increases insubcutaneous adipose tissue vs. visceral fat; this

distinction requires CT or MRI.

Increased Waist Circumference


19/56

ETIOLOGY

With increases in visceral adipose tissue, adiposetissuederived FFAs are directed to the liver. On the other

hand, increases in abdominal subcutaneous fat releaselipolysis productsinto the systemic circulation and avoid

more direct effects on hepatic metabolism



20/56

ETIOLOGY

Relative increases in visceral versus subcutaneousadipose tissue with increasing waist circumference in

Asians and Asian Indians may explain the greaterprevalence of the syndrome in these populations

compared to African-American men in whomsubcutaneous fat predominates.



21/56

ETIOLOGY

The other major lipoprotein disturbance in the metabolicsyndrome is a reduction in HDL cholesterol. This

reduction is aconsequence of changes in HDL

composition and metabolism

Dyslipidemia


22/56

ETIOLOGY

The defects in insulin action lead to impaired suppressionof glucose production by the liver and kidney and

reduced glucose uptake and metabolism in insulinsensitive

tissues, i.e., muscle and adipose tissue.

Glucose Intolerance


23/56

ETIOLOGY

To compensate for defects in insulin action, insulinsecretion and/or clearance must be modified to

sustain euglycemia. Ultimately, this compensatorymechanism fails, usually because of defects in insulin

secretion, resulting in progress from IFG and/or IGT toDM.

Glucose Intolerance


24/56

ETIOLOGY

The relationship between insulin resistance andhypertension is well established. Paradoxically, undernormal physiologic conditions, insulin is a vasodilatorwith secondary effects on sodium reabsorption in the

kidney

Hypertension


25/56

ETIOLOGY

However, in the setting of insulin resistance, thevasodilatory effect of insulin is lost, but the renal effect on

sodium reabsorption is preserved. Sodium reabsorptionis increased in Caucasians with the metabolic syndrome

but not in Africans or Asians.

Hypertension


26/56

ETIOLOGY

Insulin also increases the activity of the sympatheticnervous system, an effect that may also be preserved in

the setting of the insulin resistance.

Hypertension


27/56


28/56

ETIOLOGY

The increases in proinflammatory cytokines, includinginterleukin (IL) 1, IL-6, IL-18, resistin, tumor necrosis

factor (TNF) a, and C-reactiveprotein (CRP), reflect overproduction by the expanded

adipose tissue mass

Proinflammatory Cytokines


29/56

ETIOLOGY

Adipose tissue-derived macrophages may be the primarysource of pro-inflammatory cytokines locally and in the

systemic circulation

Proinflammatory Cytokines


30/56

ETIOLOGY

Adiponectin is an anti-inflammatory cytokine producedexclusively by adipocytes.

Adiponectin enhances insulin sensitivity and

inhibits many steps in the inflammatory process.

Adeponectine


31/56

ETIOLOGY

In the liver, adiponectin inhibits the expression ofgluconeogenic enzymes and the rate of glucose

production.In muscle, adiponectin increases glucose transport and

enhances fatty acid oxidation, partially due to activationof AMP kinase.

Adeponectine


32/56

ETIOLOGY

Adiponectin is reduced in the metabolic syndrome.

Adeponectine


33/56

CLINICAL FEATURES

The metabolic syndrome is typically unassociated withsymptoms.

On physical examination, waist circumference may be

expanded and blood pressure elevated.

Symptoms and Signs


34/56

CLINICAL FEATURES

Less frequently, lipoatrophy or acanthosis nigricans isfound on exam. Because these physical findings are

typically associated with severe insulin resistance, othercomponents of the metabolic syndrome should be

expected.

Symptoms and Signs


35/56

CLINICAL FEATURES

CARDIOVASCULAR DISEASE The relative risk for new-onset CVD in patients with the

metabolic syndrome, in the absence of diabetes,averages between 1.5- and threefold.

Associated Diseases


36/56

CLINICAL FEATURES

CARDIOVASCULAR DISEASEIn an 8-year follow-up of middle-aged men and women in

the Framingham Offspring Study (FOS), the populationattributable risk for patients with the metabolic

syndrome to develop CVD was 34% in menand 16% in women.

Associated Diseases


37/56

CLINICAL FEATURES

CARDIOVASCULAR DISEASEBoth the metabolic syndrome and diabetes predictedischemic stroke with greater risk for patients with themetabolic syndrome than for diabetes alone (19% vs

7%), particularly in women (27% vs 5%).

Associated Diseases


38/56

CLINICAL FEATURES

CARDIOVASCULAR DISEASEPatients with metabolic syndrome are also at increased

risk for peripheral vascular disease.

Associated Diseases


39/56

CLINICAL FEATURES

Type 2 DiabetesOverall, the risk for type 2 diabetes in patients with themetabolic syndrome is increased three- to fivefold. In theFOSs 8- year follow-up of middle-aged men and women,

the population-attributable risk for developing type 2diabetes was 62% in men and 47% in women.

Associated Diseases


40/56

CLINICAL FEATURES

Nonalcoholic Fatty Liver DiseaseFatty liver is relatively common. However, in NASH, both

triglyceride accumulation and inflammation coexist.NASH is now present in 23% of the population in the

United States and other Western countries.

Associated Diseases


41/56

CLINICAL FEATURES

HyperuricemiaHyperuricemia reflects defects in insulin action on the

renal tubular reabsorption of uric acid.

Associated Diseases


42/56

CLINICAL FEATURES

Polycystic Ovarian SyndromePCOS is highly associated with the metabolic syndrome,

with a prevalence between 40 and 50%. Women withPCOS are 24 times more likely to have the metabolic

syndrome compared to women without PCOS.

Associated Diseases


43/56

CLINICAL FEATURES

Obstructive Sleep ApneaOSA is commonly associated with obesity, hypertension,

increased circulating cytokines, IGT, and insulinresistance.

With these associations, it is not surprising that themetabolic syndrome is frequently present

Associated Diseases


44/56

DIAGNOSIS


45/56

DIAGNOSIS

The medical history should include evaluationof symptoms for OSA in all patients and PCOS in

premenopausal women. Family history will help Themedical history should include evaluation of symptoms

for OSA in all patients and PCOS in premenopausalwomen. Family history will help determin


46/56

DIAGNOSIS

Fasting lipids and glucose are needed to determine if themetabolic syndrome is present.

Measuring apo B, high-sensitivity CRP, fibrinogen, uric

acid, urinary microalbumin, and liver function tests.

Laboratory Tests


47/56

DIAGNOSIS

A sleep study should be performed if symptoms of OSAare present. If PCOS is suspected based on clinicalfeatures and anovulation, testosterone, luteinizing

hormone, and follicle-stimulating hormone should be

measured.

Laboratory Tests


48/56

TREATMENT AND PREVENTION

Lifestyle. Diet.

Physical Activity. Obesity. LDL Cholesterol. Triglycerides. HDL Cholesterol. Blood Pressure. Impaired Fasting Glucose. Insuline Resistance.


49/56


Weight reduction is the primary approach to the disorder.

With weight reduction, the improvement in insulinsensitivity is often accompanied by favorable

modifications in many components of the metabolicsyndrome.

Lifestyle


50/56


On the basis of ~3500 kcal = one lb of fat, ~500 kcalrestriction daily equates to a weight reduction of 1 lb per

week. Diets restricted in carbohydrate typically provide arapid initial weight loss.

However, after one year, the amount of weight reductionis usually unchanged. Thus, adherence to the diet is

more important than which diet is chosen.

Diet

O


51/56


Before a physical activity recommendation is provided to

patients with the metabolic syndrome, it is important to

ensure that this increased activity does not incur risk.

For the inactive participant, gradual increases in physical

activity should be encouraged to enhance adherence and

to avoid injury.

Physical Activit



52/56


Although increases in physical activity can lead to modest

weight reduction, 6090 min of daily activity is requiredto achieve this goal. Even if an overweight or obeseadult is unable to achieve this level of activity, they still

derive a significant health benefit from at least 30 min ofmoderate intensity daily activity.

Physical Activit



53/56


Weight-loss drugs come in two major classes: appetite

suppressants and absorption inhibitors

Appetite suppressants approved by the Food and DrugAdministration include phentermine (for short-term use

only, 3 months) and sibutramine.

Obesity



54/56


Orlistat inhibits fat absorption by ~30% and is moderately

effective compared to placebo (~5% weight loss).Orlistat has been shown to reduce the incidence of type

2 diabetes, an effect that was especially evident inpatients with baseline IGT.

Obesity



55/56


Bariatric surgery is an option for patients with themetabolic syndrome who have a body mass index (BMI)

of >40 kg/m2 or >35 kg/m2 with comorbidities.Gastric bypass results in a dramatic weight reduction and

improvement in the features of metabolic syndrome. Atpresent, however, a survival benefit has yet to be

realized.

Obesity



56/56


For patients with the metabolic syndrome and diabetes,LDL cholesterol should be reduced to

Presentation Metabolic Syndrome

Documents

Transcript of Presentation Metabolic Syndrome