Metabolic_syndrome

Dysmetabolic syndrome X Classification & external resources
ICD-9	277.7
OMIM	605552
DiseasesDB	31955
MeSH	D024821

Metabolic syndrome is a combination of medical disorders that increase the risk of developing cardiovascular disease and diabetes. It affects a large number of people, and prevalence increases with age. Some studies estimate the prevalence in the USA to be up to 25% of the population.^{[citation needed]}

Metabolic syndrome is also known as metabolic syndrome X, syndrome X, insulin resistance syndrome, Reaven\'s syndrome or CHAOS (Australia). A similar condition in overweight horses is referred to as equine metabolic syndrome; it is unknown if they have the same etiology.

Contents 1 Signs and symptoms 2 Diagnosis 2.1 WHO 2.2 EGIR 2.3 NCEP 2.4 American Heart Association/Updated NCEP 3 Etiology 4 Pathophysiology 5 Prevention 6 Therapy 7 History 8 See also 9 References

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;

Associated diseases and signs are: elevated uric acid levels, 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).

Diagnosis

There are currently two major definitions for metabolic syndrome provided by the International Diabetes FederationThe IDF consensus worldwide definition of the metabolic syndrome. PDF and 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 cut points for waist circumference, while NCEP uses only one set of cut points for waist circumference regardless of geography. These two definitions are much closer to each other than the original NCEP and WHO definitions.

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 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

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

• 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 confusion as to whether AHA/NHLBI intended to create another set of guidelines or simply update the NCEP ATP III definition. According to Scott Grundy, University of Texas Southwestern Medical School, Dallas, Texas, the intent was just to update the NCEP ATP III definition and not create a new definition.Grundy SM, Brewer HB, Cleeman JI, Smith SC, Lenfant D, for the Conference Participants. Definition of metabolic syndrome: report of the National, Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation. 2004;109:433-438.American Heart Association\'s description of Syndrome X:

• 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 cause of the metabolic syndrome is unknown. The pathophysiology is extremely complex and has been only partially elucidated. Most patients are older, obese, sedentary, and have a degree of insulin resistance. The most important factors in order are:

1. aging,
2. genetics and
3. lifestyle, i.e., low physical activity and excess caloric intake.

There is debate regarding whether obesity or insulin resistance is the cause of the metabolic syndrome or if they are consequences of a more far-reaching metabolic derangement. However, metabolic syndrome is not observed in the absence of insulin resistance, while obesity is not present in many individuals who present with metabolic syndrome. A number of markers of systemic inflammation, 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 increased uric acid levels caused by dietary fructose.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. Hallfrisch J (1990). "Metabolic effects of dietary fructose". FASEB J 4 (9): 2652–2660. PMID 2189777. 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. 

Pathophysiology

Commonly there is development of visceral fat after which the adipocytes (fat cells) of the visceral fat increase plasma levels of TNFα and alter levels of a number of other substances (e.g., adiponectin, resistin, PAI-1). TNFα has been shown not only to cause the production of inflammatory cytokines, but possibly to trigger cell signalling by interaction with a TNFα receptor that may lead to insulin resistance^{[citation needed]}. 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 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. . The progression from visceral fat to increased TNFα to insulin resistance has some parallels to human development of metabolic syndrome.

Prevention

Various strategies have been proposed to prevent the development of metabolic syndrome. These include increased physical activity (such as walking 30 minutes every day),Lakka TA, Laaksonen DE (2007). "Physical activity in prevention and treatment of the metabolic syndrome". Applied physiology, nutrition, and metabolism = Physiologie appliquée, nutrition et métabolisme 32 (1): 76-88. doi:10.1139/h06-113. PMID 17332786.  and a healthy, reduced calorie diet.Feldeisen SE, Tucker KL (2007). "Nutritional strategies in the prevention and treatment of metabolic syndrome". Appl Physiol Nutr Metab 32 (1): 46-60. doi:10.1139/h06-101. PMID 17332784.  There are many studies that support the value of a healthy lifestyle as above. However, one study stated that these measures are effective in only a minority of people. The International Obesity Taskforce states that interventions on a sociopolitical level are required to reduce development of the metabolic syndrome in populations.James PT, Rigby N, Leach R (2004). "The obesity epidemic, metabolic syndrome and future prevention strategies". Eur J Cardiovasc Prev Rehabil 11 (1): 3-8. PMID 15167200. 

A 2007 study of 2,375 male subjects over 20 years suggested that daily intake of a pint of milk or equivalent dairy products more than halved the risk of metabolic syndrome.Elwood, PC; Pickering JE, Fehily AM (2007). "Milk and dairy consumption, diabetes and the metabolic syndrome: the Caerphilly prospective study". J Epidemiol Community Health 61 (8): 695-698. doi:10.1136/jech.2006.053157. PMID 17630368.  Other studies both support and dispute the authors\' findings.Snijder MB, van der Heijden AA, van Dam RM, et al (2007). "Is higher dairy consumption associated with lower body weight and fewer metabolic disturbances? The Hoorn Study". Am. J. Clin. Nutr. 85 (4): 989-95. PMID 17413097. 

Therapy

The first line treatment is change of lifestyle (i.e., caloric restriction and physical activity). However, drug treatment is frequently required. Generally, the individual disorders that comprise the metabolic syndrome are treated separately. Diuretics and ACE inhibitors may be used for hypertension). Cholesterol drugs may be used to lower LDL cholesterol and triglyceride levels, if they are elevated, and to raise HDL levels if they are low. Use of drugs that decrease insulin resistance e.g., metformin and thiazolidinediones, is controversial; this treatment is not approved by the FDA in the US.

A 2003 study indicated that cardiovascular exercise was therapeutic in approximately 31% of cases. The most probable benefit was to triglyceride levels, with 43% showing improvement; but fasting plasma glucose and insulin resistance of 91% of test subjects did not improve.Katzmaryk,, Peter T; Leon, Arthur S.; Wilmore, Jack H.; Skinner, James S.; Rao, D. C.; Rankinen, Tuomo; Bouchard, Claude (October 2003). "Targeting the Metabolic Syndrome with Exercise: Evidence from the HERITAGE Family Study.". Med. Sci. Sports Exerc 35 (10): 1703-1709. Retrieved on 2007-06-24.  Many other studies have supported the value of increased physical activity and restricted caloric intake (exercise and diet) to treat metabolic syndrome.

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.Joslin EP. The prevention of diabetes mellitus. JAMA 1921;76:79–84.Kylin E. [Studies of the hypertension-hyperglycemia-hyperuricemia syndrome] (German). Zentralbl Inn Med 1923;44: 105-27.

• 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.Vague J. La diffférenciacion sexuelle, facteur déterminant des formes de l\'obésité. Presse Med 1947;30:339-40.
• 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.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.
• 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.Haller H. [Epidemiology and associated risk factors of hyperlipoproteinemia] (German). Z Gesamte Inn Med 1977;32(8):124-8. PMID 883354.
• The same year, Singer used the term for associations of obesity, gout, diabetes mellitus, and hypertension with hyperlipoprotenemia.Singer P. [Diagnosis of primary hyperlipoproteinemias] (German). Z Gesamte Inn Med 1977;32(9):129-33. PMID 906591.
• In 1977 and 1978, 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.Phillips GB. Sex hormones, risk factors and cardiovascular disease. Am J Med 1978;65:7-11. PMID 356599.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.
• In 1988, in his Banting lecture, 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.Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 1988;37:1595-607. PMID 3056758.

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).

See also

• Hyperinsulinemia
• Insulin resistance
• Chronic Somogyi rebound

References

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