Syndrome x

The syndrome runs in families and is more common among African-Americans, Hispanics, Asians, and Native Americans.

Metabolic syndrome, also called Syndrome X is a group of risk factors that together, put someone at higher risk of coronary artery disease. These risk factors include: central obesity (excessive fat tissue in the abdominal region), glucose intolerance, high triglycerides and low hdl cholesterol, and high blood pressure.

Risk Factors for Metabolic Syndrome[edit | edit source]

Insulin resistance--Insulin is a hormone that helps your body use glucose -- a simple sugar made from the food you eat -- as energy. In people with insulin resistance, the insulin doesn't work as well, so your body keeps making more and more of it to cope with the rising level of glucose. Eventually, this can lead to diabetes. Insulin resistance is closely connected to having excess weight in the belly.

Obesity -- especially abdominal obesity. Experts say that metabolic syndrome is becoming more common because of rising obesity rates. In addition, having extra fat in the belly -- as opposed to elsewhere in the body -- seems to increase your risk.
Unhealthy lifestyle--Eating a diet high in unhealthy processed foods and not getting enough physical activity can play a role.
Hormonal imbalance--Hormones may play a role. For instance, polycystic ovary syndrome (PCOS) -- a condition that affects fertility -- is related to hormonal imbalance and metabolic syndrome.
Smoking.

Aging
Diabetes mellitus type 2: The metabolic syndrome quintuples the risk of type 2 diabetes mellitus. Type 2 diabetes is considered a complication of metabolic syndrome.
Coronary heart disease
Lipodystrophy
Rheumatic diseases

Pathophysiology[edit | edit source]

It is common for there to be a development of visceral fat, after which the adipocytes (fat cells) of the visceral fat increase plasma levels of TNF-α and alter levels of other substances (e.g., adiponectin, resistin, and PAI-1). TNF-α has been shown to cause the production of inflammatory cytokines and also possibly trigger cell signaling by interaction with a TNF-α receptor that may lead to insulin resistance. An experiment with rats fed a diet with 33% 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 TNF-α to insulin resistance has some parallels to human development of metabolic syndrome. The increase in adipose tissue also increases the number of immune cells, which play a role in inflammation. Chronic inflammation contributes to an increased risk of hypertension, atherosclerosis and diabetes.

The involvement of the endocannabinoid system in the development of metabolic syndrome is indisputable. Endocannabinoid overproduction may induce reward system dysfunction and cause executive dysfunctions (e.g., impaired delay discounting), in turn perpetuating unhealthy behaviors.[medical citation needed] The brain is crucial in development of metabolic syndrome, modulating peripheral carbohydrate and lipid metabolism.

Metabolic syndrome can be induced by overfeeding with sucrose or fructose, particularly concomitantly with high-fat diet. The resulting oversupply of omega-6 fatty acids, particularly arachidonic acid (AA), is an important factor in the pathogenesis of metabolic syndrome.[medical citation needed] Arachidonic acid (with its precursor – linoleic acid) serves as a substrate to the production of inflammatory mediators known as eicosanoids, whereas the arachidonic acid-containing compound diacylglycerol (DAG) is a precursor to the endocannabinoid 2-arachidonoylglycerol (2-AG) while fatty acid amide hydrolase (FAAH) mediates the metabolism of anandamide into arachidonic acid. Anandamide can also be produced from N-acylphosphatidylethanolamine via several pathways. Anandamide and 2-AG can also be hydrolyzed into arachidonic acid, potentially leading to increased eicosanoid synthesis.

Criteria for Diagnosis[edit | edit source]

IDF: The International Diabetes Federation consensus worldwide definition of metabolic syndrome (2006) is: 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 (BP): 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 is >5.6 mmol/L or 100 mg/dL, an oral 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

WHO: The World Health Organization (1999)[44] requires the presence of any 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 HDL cholesterol ≤ 0.9 mmol/L (male), ≤ 1.0 mmol/L (female)
Central obesity: waist:hip ratio > 0.90 (male); > 0.85 (female), or BMI > 30 kg/m2
Microalbuminuria: urinary albumin excretion ratio ≥ 20 µg/min or albumin:creatinine ratio ≥ 30 mg/g

EGIR: The European Group for the Study of Insulin Resistance (1999) requires insulin resistance defined as the top 25% of the fasting insulin values among nondiabetic individuals AND two or more of the following:

Central obesity: waist circumference ≥ 94 cm or 37 inches (male), ≥ 80 cm or 31.5 inches (female)
Dyslipidemia: TG ≥ 2.0 mmol/L and/or HDL-C < 1.0 mmol/L or treated for dyslipidemia
Blood pressure ≥ 140/90 mmHg or antihypertensive medication
Fasting plasma glucose ≥ 6.1 mmol/L

NCEP: The U.S. National Cholesterol Education Program Adult Treatment Panel III (2001) requires at least three of the following:

Central obesity: waist circumference ≥ 102 cm or 40 inches (male), ≥ 88 cm or 35 inches(female)
Dyslipidemia: TG ≥ 1.7 mmol/L (150 mg/dl)
Dyslipidemia: HDL-C < 40 mg/dL (male), < 50 mg/dL (female)
Blood pressure ≥ 130/85 mmHg (or treated for hypertension)
Fasting plasma glucose ≥ 6.1 mmol/L (110 mg/dl)

American Heart Association: There is confusion as to whether, in 2004, the American Heart Association and National Heart, Lung, and Blood Institute intended to create another set of guidelines or simply update the National Cholesterol Education Program definition.

Central obesity: waist circumference ≥ 102 cm or 40 inches (male), ≥ 88 cm or 35 inches(female)
Dyslipidemia: TG ≥ 1.7 mmol/L (150 mg/dL)
Dyslipidemia: HDL-C < 40 mg/dL (male), < 50 mg/dL (female)
Blood pressure ≥ 130/85 mmHg (or treated for hypertension)
Fasting plasma glucose ≥ 5.6 mmol/L (100 mg/dL), or use of medication for hyperglycemia

Other

High-sensitivity C-reactive protein has been developed and used as a marker to predict coronary vascular diseases in metabolic syndrome, and it was recently used as a predictor for nonalcoholic fatty liver disease (steatohepatitis) in correlation with serum markers that indicated lipid and glucose metabolism.[48] Fatty liver disease and steatohepatitis can be considered manifestations of metabolic syndrome, indicative of abnormal energy storage as fat in ectopic distribution. Reproductive disorders (such as polycystic ovary syndrome in women of reproductive age), and erectile dysfunction or decreased total testosterone (low testosterone-binding globulin) in men can be attributed to metabolic syndrome.

Prevention[edit | edit source]

Various strategies have been proposed to prevent the development of metabolic syndrome. These include increased physical activity (such as walking 30 minutes every day),[50] and a healthy, reduced calorie diet. Many studies support the value of a healthy lifestyle as above. However, one study stated these potentially beneficial measures are effective in only a minority of people, primarily because of a lack of compliance with lifestyle and diet changes. The International Obesity Taskforce states that interventions on a sociopolitical level are required to reduce development of the metabolic syndrome in populations.

The Caerphilly Heart Disease Study followed 2,375 male subjects over 20 years and suggested the daily intake of a pint (~568 mL) of milk or equivalent dairy products more than halved the risk of metabolic syndrome. Some subsequent studies support the authors' findings, while others dispute them. A systematic review of four randomized controlled trials said that, in the short term, a paleolithic nutritional pattern improved three of five measurable components of the metabolic syndrome in participants with at least one of the components.

Management[edit | edit source]

Generally, the individual disorders that compose the metabolic syndrome are treated separately. Diuretics and ACE inhibitors may be used to treat hypertension. Various cholesterol medications may be useful if LDL cholesterol, triglycerides, and/or HDL cholesterol is abnormal. Dietary carbohydrate restriction reduces blood glucose levels, contributes to weight loss, and reduces the use of several medications that may be prescribed for metabolic syndrome.