Metabolic syndrome is a combination of medical disorders that increase one's risk for cardiovascular disease and diabetes. It affects a large number of people in a clustered fashion. In some studies, the prevalence in the USA is calculated as being up to 25% of the population. The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or disease. ... The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. ... The Mendelian Inheritance in Man project is a database that catalogues all the known diseases with a genetic component, and - when possible - links them to the relevant genes in the human genome. ... The Disease Bold textDatabase is a free website that provides information about the relationships between medical conditions, symptoms, and medications. ... medicines, see medication and pharmacology. ... Cardiovascular disease refers to the class of diseases that involve the heart and/or blood vessels (arteries and veins). ... For the disease characterized by excretion of large amounts of very dilute urine, see diabetes insipidus. ... In epidemiology, the prevalence of a disease in a statistical population is defined as the ratio of the number of cases of a disease present in a statistical population at a specified time and the number of individuals in the population at that specified time. ...

It is known under various other names, such as (metabolic) syndrome X, insulin resistance syndrome, Reaven's syndrome or CHAOS (Australia). Insulin resistance is the condition in which normal amounts of insulin are inadequate to produce a normal insulin response from fat, muscle and liver cells. ... Gerald Reaven is an American endocrinologist and professor emeritus in medicine at the Stanford University School of Medicine in Stanford, California. ...

Signs and symptoms

Symptoms and features are:

• 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;
• Elevated uric acid levels.

Associated diseases and signs are: fatty liver (especially in concurrent obesity), progressing to non-alcoholic fatty liver disease, polycystic ovarian syndrome, hemochromatosis (iron overload); and acanthosis nigricans (a skin condition featuring dark patches). See diabetes mellitus for further general information on diabetes. ... Impaired fasting glycaemia (IFG) is a pre-diabetic state, associated with insulin resistance and increased risk cardiovascular pathology, although of lesser risk that Impaired glucose tolerance (IGT). ... Impaired Glucose Tolerance (IGT) is a pre-diabetic state of dysglycemia, that is associated with insulin resistance and increased risk of cardiovascular pathology. ... Insulin resistance is the condition in which normal amounts of insulin are inadequate to produce a normal insulin response from fat, muscle and liver cells. ... Arterial hypertension, or high blood pressure is a medical condition where the blood pressure is chronically elevated. ... Central obesity (or apple-shaped or masculine obesity) occurs when the main deposits of body fat are localised around the abdomen and the upper body. ... High-density lipoproteins (HDL) form a class of lipoproteins, varying somewhat in their size (8–11 nm in diameter), that carry cholesterol from the bodys tissues to the liver. ... It has been suggested that Medium Chain Triglycerides be merged into this article or section. ... This article or section is in need of attention from an expert on the subject. ... Fatty liver (also known as steatorrhoeic hepatosis or steatosis hepatis) is a reversible condition where large vacuoles of triglyceride fat accumulate in liver cells via the process of steatosis. ... Non-alcoholic fatty liver disease (NAFLD) is fatty inflammation of the liver when this is not due to excessive alcohol use. ... Polycystic ovary syndrome (PCOS, also known clinically as Stein-Leventhal syndrome), is an endocrine disorder that affects 5–10% of women. ... Haemochromatosis, also spelled hemochromatosis, is a hereditary disease characterized by improper processing by the body of dietary iron which causes iron to accumulate in a number of body tissues, eventually causing organ dysfunction. ... Acanthosis nigricans is a brown to black, poorly defined, velvety hyperpigmentation of the skin, usually present in the posterior and lateral folds of the neck, the axilla, groin, umbilicus, and other areas. ...

Diagnosis

There are currently two major definitions for metabolic syndrome: 1)International Diabetes Federation^[1] and 2) the revised National Cholesterol Education Program, respectively. The revised NCEP and IDF definitions of metabolic syndrome are very similar and it can be expected that they will identify many of the same individuals as having metabolic syndrome. The two differences are that IDF excludes any subject without increased waist circumference, while in the NCEP definition metabolic syndrome can be diagnosed based on other criteria and the IDF uses geography-specific cutpoints for waist circumference, while NCEP uses only one set of cutpoints for waist circumference regardless of geography. These two definitions are much closer to each other than the original NCEP and WHO definitions. The International Diabetes Federation (IDF) is the global advocate for more than 230 million people with diabetes worldwide. ... The National Cholesterol Education Program is a program managed by the National Heart, Lung and Blood Institute, a division of the National Institutes of Health. ...

WHO

The World Health Organization criteria (1999) require presence of diabetes mellitus, impaired glucose tolerance, impaired fasting glucose or insulin resistance, AND two of the following:

• blood pressure: ≥ 140/90 mmHg
• dyslipidaemia: triglycerides (TG): ≥ 1.695 mmol/L and/or 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), and/or body mass index > 30 kg/m2
• microalbuminuria: urinary albumin excretion ratio ≥ 20 mg/min or albumin:creatinine ratio ≥ 30 mg/g

EGIR

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

• central obesity: waist circumference ≥ 94 cm (male), ≥ 80 cm (female)
• dyslipidaemia: TG ≥ 2.0 mmol/L and/or HDL-C < 1.0 mg/dL or treated for dyslipidaemia
• hypertension: blood pressure ≥ 140/90 mmHg or antihypertensive medication
• fasting plasma glucose ≥ 6.1 mmol/L

NCEP

The National Cholesterol Education Program Adult Treatment Panel III (2001) requires at least three of the following:^[2]

• central obesity: waist circumference ≥ 102 cm or 40 inches (male), ≥ 88 cm or 36 inches(female)
• dyslipidaemia: TG ≥ 1.695 mmol/L (150 mg/dl)
• dyslipidaemia: HDL-C < 40 mg/dL (male), < 50 mg/dL (female)
• blood pressure ≥ 130/85 mmHg
• fasting plasma glucose ≥ 6.1 mmol/L (110 mg/dl)

American Heart Association/Updated NCEP

There is quite a bit of confusion about whether AHA/NHLBI intended to create another set of guidelines or simply update the NCEP ATPIII definition. According to Dr. Scott Grundy, University of Texas Southwestern Medical School, Dallas, Texas, the intent was just to update the NCEP ATPIII definition and not create a new definition (personal communication):

• Elevated waist circumference: Men — Equal to or greater than 40 inches (102 cm) Women — Equal to or greater than 35 inches (88 cm)
• Elevated triglycerides: Equal to or greater than 150 mg/dL
• Reduced HDL (“good”) cholesterol: Men — Less than 40 mg/dL Women — Less than 50 mg/dL
• Elevated blood pressure: Equal to or greater than 130/85 mm Hg or use of medication for hypertension
• Elevated fasting glucose: Equal to or greater than 100 mg/dL (5.6 mmol/L) or use of medication for hyperglycemia

Etiology

The causes of metabolic syndrome are extremely complex and have only been partially elucidated. Most patients are older, obese and have a degree of insulin resistance. The most important factors in order are 1) aging, 2) lifestyle (i.e., physical activity and caloric intake) and 3) genetics. There is debate regarding whether obesity or insulin resistance is the cause of the metabolic syndrome or a by-product of a more far-reaching metabolic derangement. Systemic inflammation: a number of inflammatory markers (including C-reactive protein) are often increased, as are fibrinogen, InterLeukin−6 (IL−6), Tumor Necrosis Factor alpha (TNFα) and others. Some have pointed to oxidative stress due to a variety of causes including dietary fructose mediated increased uric acid levels.^[3][4][5] Insulin resistance is the condition in which normal amounts of insulin are inadequate to produce a normal insulin response from fat, muscle and liver cells. ... An abscess on the skin, showing the redness and swelling characteristic of inflammation. ... C-reactive protein (CRP) is a plasma protein, an acute phase protein produced by the liver. ... Fibrin is a protein involved in the clotting of blood. ... Interleukins are a group of cytokines that were first seen to be expressed by white blood cells (leukocytes, hence the -leukin) as a means of communication (inter-). The name is sort of a relic though; it has since been found that interleukins are produced by a wide variety of bodily... In medicine, tumor necrosis factor alpha (TNFα, cachexin or cachectin) is an important cytokine involved in systemic inflammation and the acute phase response. ... Oxidative stress is a medical term for damage to animal or plant cells (and thereby the organs and tissues composed of those cells) caused by reactive oxygen species, which include (but are not limited to) superoxide, singlet oxygen, peroxynitrite or hydrogen peroxide. ... Fructose (or levulose) is a simple sugar (monosaccharide) found in many foods and is one of the three most important blood sugars along with glucose and galactose. ...

Pathophysiology

Commonly, there is development of visceral fat followed by the adipocytes (fat cells) of the visceral fat increasing plasma levels of TNFα and altering levels of a number of other substances (e.g., adiponectin, resistin, PAI-1). TNFα has been shown to not only cause the production of inflammatory cytokines, but may also trigger cell signalling by interaction with a TNFα receptor that may lead to insulin resistance. An experiment with rats that were fed a diet one-third of which was sucrose has been proposed as a model for the development of the metabolic syndrome. The sucrose first elevated blood levels of triglycerides, which induced visceral fat and ultimately resulted in insulin resistance ^[6]. The progression from visceral fat to increased TNFα to insulin resistance parallels human development of metabolic syndrome. A term often used in usability enginering or user interface design Often conected with the Emotional feelings in a product signifies the WOW feeling when seeing a new product. ... Fats consist of a wide group of compounds that are generally soluble in organic solvents and largely insoluble in water. ... Adipocytes are the cells that primarily compose adipose tissue, specialized in storing energy as fat. ... Drawing of the structure of cork as it appeared under the microscope to Robert Hook from Micrographia which is the origin of the word cell. Cells in culture, stained for keratin (red) and DNA (green). ... Blood plasma is the liquid component of blood, in which the blood cells are suspended. ... Cytokines are a group of proteins and peptides that are used in organisms as signaling compounds. ... In biochemistry, a receptor is a protein on the cell membrane or within the cytoplasm or cell nucleus that binds to a specific molecule (a ligand), such as a neurotransmitter, hormone, or other substance, and initiates the cellular response to the ligand. ... Sucrose (common name: table sugar, also called saccharose) is a disaccharide (glucose + fructose) with the molecular formula C12H22O11. ... It has been suggested that Medium Chain Triglycerides be merged into this article or section. ... A term often used in usability enginering or user interface design Often conected with the Emotional feelings in a product signifies the WOW feeling when seeing a new product. ...

Therapy

The main treatment is lifestyle (i.e., caloric restriction and physical activity). However, drug treatment may occasionally be necessary. Generally, the individual diseases that comprise the metabolic syndrome are treated separately (e.g. diuretics and ACE inhibitors for hypertension). Cholesterol drugs may be used to lower LDL cholesterol and triglyceride levels, if they are elevated. Use of drugs that decrease insulin resistance e.g., metformin and thiazolidinediones is controversial and not FDA approved. A diuretic (colloquially called a water pill) is any drug or herb that elevates the rate of bodily urine excretion (diuresis). ... Captopril, the first ACE inhibitor ACE inhibitors, or inhibitors of Angiotensin-Converting Enzyme, are a group of pharmaceuticals that are used primarily in treatment of hypertension and congestive heart failure, in most cases as the drugs of first choice. ... This article or section does not adequately cite its references or sources. ... Insulin resistance is the condition in which normal amounts of insulin are inadequate to produce a normal insulin response from fat, muscle and liver cells. ... Metformin (INN; trade names Glucophage, Diabex, Diaformin, Fortamet, Riomet, Glumetza and others) is an anti-diabetic drug from the biguanide class of oral hypoglycemic agents. ... The medication class of thiazolidinedione was introduced in the late 1990s as an adjunctive therapy for diabetes mellitus (type II) and related diseases. ...

History

The term "metabolic syndrome" dates back to at least the late 1950s, but came into common usage in the late 1970s to describe various associations of risk factors with diabetes, that had been noted as early as the 1920s.^[7][8]

• The Marseilles physician Dr. Jean Vague, in 1947, made the interesting observation that upper body obesity appeared to predispose to diabetes, atherosclerosis, gout, and calculi.^[9]
• Avogaro, Crepaldi and co-workers described six moderately obese patients with diabetes, hypercholesterolemia, and marked hypertriglyceridemia all of which improved when the patients were put on a hypocaloric, low carbohydrate diet.^[10]
• In 1977, Haller used the term "metabolic syndrome" for associations of obesity, diabetes mellitus, hyperlipoproteinemia, hyperuricemia and steatosis hepatis when describing the additive effects of risk factors on atherosclerosis.^[11]
• The same year, Singer used the term for associations of obesity, gout, diabetes mellitus, and hypertension with hyperlipoprotenemia.^[12]
• In 1977 and 1978, Dr. Gerald B. Phillips developed the concept that risk factors for myocardial infarction concur to form a "constellation of abnormalities" (i.e., glucose intolerance, hyperinsulinemia, hyperlipidemia [hypercholesterolemia and hypertriglyceridemia] and hypertension) that is associated not only with heart disease, but also with aging, obesity and other clinical states. He suggested there must be an underlying linking factor, the identification of which could lead to the prevention of cardiovascular disease; he hypothesized that this factor was sex hormones.^[13][14]
• In 1988, in his Banting lecture, Dr. Gerald M. Reaven proposed insulin resistance as the underlying factor and named the constellation of abnormalities Syndrome X. Reaven did not include abdominal obesity, which has also been hypothesized as the underlying factor, as part of the condition.^[15]

The terms "metabolic syndrome", "insulin resistance syndrome", and "syndrome X" are now used specifically to define a constellation of abnormalities that is associated with increased risk for the development of type 2 diabetes and atherosclerotic vascular disease (e.g. heart disease and stroke). Gerald M. Jerry Reaven is an American endocrinologist and professor emeritus in medicine at the Stanford University School of Medicine in Stanford, California. ...

See also

• Hyperinsulinemia
• Insulin resistance
• Uric acid

Hyperinsulinemia, present in people with Diabetes mellitus type 2 or insulin resistance where excess levels of circulating insulin in blood. ... Insulin resistance is the condition in which normal amounts of insulin are inadequate to produce a normal insulin response from fat, muscle and liver cells. ... This article or section is in need of attention from an expert on the subject. ...

References

1. ^ The IDF consensus worldwide definition of the metabolic syndrome. PDF
2. ^ Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA 2001;285:2486-97. PMID 11368702.
3. ^ Nakagawa T, Hu H, Zharikov S, Tuttle KR, Short RA, Glushakova O, Ouyang X, Feig DI, Block ER, Herrera-Acosta J, Patel JM, Johnson RJ (2006). "A causal role for uric acid in fructose-induced metabolic syndrome". Am J Phys Renal Phys 290 (3): F625–F631. PMID 16234313. 
4. ^ Hallfrisch J (1990). "Metabolic effects of dietary fructose". FASEB J 4 (9): 2652–2660. PMID 2189777. 
5. ^ Reiser S, Powell AS, Scholfield DJ, Panda P, Ellwood KC, Canary JJ (1989). "Blood lipids, lipoproteins, apoproteins, and uric acid in men fed diets containing fructose or high-amylose cornstarch". Am J Clin Nutr 49 (5): 832–839. PMID 2497634. 
6. ^ Fukuchi S, Hamaguchi K, Seike M, Himeno K, Sakata T, Yoshimatsu H. (2004). "Role of Fatty Acid Composition in the Development of Metabolic Disorders in Sucrose-Induced Obese Rats". Exp Biol Med 229 (6): 486–493. PMID 15169967. 
7. ^ Joslin EP. The prevention of diabetes mellitus. JAMA 1921;76:79–84.
8. ^ Kylin E. [Studies of the hypertension-hyperglycemia-hyperuricemia syndrome] (German). Zentralbl Inn Med 1923;44: 105-27.
9. ^ Vague J. La diffférenciacion sexuelle, facteur déterminant des formes de l'obésité. Presse Med 1947;30:339-40.
10. ^ Avogaro P, Crepaldi G, Enzi G, Tiengo A. Associazione di iperlipidemia, diabete mellito e obesità di medio grado. Acta Diabetol Lat 1967;4:572-590.
11. ^ Haller H. [Epidemiology and associated risk factors of hyperlipoproteinemia] (German). Z Gesamte Inn Med 1977;32(8):124-8. PMID 883354.
12. ^ Singer P. [Diagnosis of primary hyperlipoproteinemias] (German). Z Gesamte Inn Med 1977;32(9):129-33. PMID 906591.
13. ^ Phillips GB. Sex hormones, risk factors and cardiovascular disease. Am J Med 1978;65:7-11. PMID 356599.
14. ^ Phillips GB. Relationship between serum sex hormones and glucose, insulin, and lipid abnormalities in men with myocardial infarction. Proc Natl Acad Sci U S A 1977;74:1729-1733. PMID 193114.
15. ^ Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 1988;37:1595-607. PMID 3056758.

• Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC Jr, Spertus JA, Costa F. Diagnosis and Management of the Metabolic Syndrome. An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 2006;113(19):2363-72. PMID 16702489.
• Grundy SM. Obesity, Metabolic Syndrome and Cardiovascular Disease. J Clin Endocrinol Metab 2004;89:2595-600. PMID 15181029.

External links

• ApolloLipids — resource for medical professionals providing articles and slides on metabolic syndrome concerning cardiovascular disease, lipids and obesity.
• American Heart Association's description of Syndrome X.