Metabolic syndrome
54439
220751734
2008-06-21T11:59:18Z
75.178.92.164
/* EGIR */
{{DiseaseDisorder infobox |
Name = Dysmetabolic syndrome X |
ICD10 = |
ICD9 = {{ICD9|277.7}} |
Image = |
Caption = |
ICDO = |
OMIM = 605552 |
DiseasesDB = 31955 |
MedlinePlus = |
eMedicineSubj = |
eMedicineTopic = |
MeshID = D024821 |
}}
'''Metabolic syndrome''' is a combination of [[medicine|medical]] disorders that increase the risk of developing [[cardiovascular disease]] and [[Diabetes mellitus|diabetes]].<ref>[http://www.nlm.nih.gov/medlineplus/metabolicsyndrome.html MedlinePlus: Metabolic Syndrome<!-- Bot generated title -->]</ref> It affects a great number of people, and prevalence increases with age. Some studies estimate the [[prevalence]] in the USA to be up to 25% of the population.<ref>Ford ES, Giles WH, Dietz WH (2002). Prevalence of metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. ''JAMA'' '''287'''(3):356-359. PMID 11790215</ref>
Metabolic syndrome is also known as '''metabolic syndrome X''', '''syndrome X''', '''[[insulin resistance]] syndrome''', '''[[Gerald Reaven|Reaven]]'s syndrome''', '''CHAOS''' (Australia), or '''metabo''' (Japan)<ref>[http://www.nytimes.com/2008/06/13/world/asia/13fat.html?ref=health New York Times: Japan, Seeking Trim Waists, Measures Millions</ref>. A similar condition in overweight horses is referred to as [[equine metabolic syndrome]]; it is unknown if they have the same [[etiology]].
== 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 [[High density lipoprotein|HDL]] cholesterol;
* Elevated [[triglyceride]]s;
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 Federation]]<ref>The IDF consensus worldwide definition of the metabolic syndrome. [http://www.idf.org/webdata/docs/IDF_Meta_def_final.pdf PDF]</ref> 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/m<sup>2</sup>
* 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 mmol/L 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:<ref>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.</ref>
* 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.<ref name="Grundy">[http://circ.ahajournals.org/cgi/reprint/109/3/433.pdf 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.</ref><ref>[http://www.americanheart.org/presenter.jhtml?identifier=4756 American Heart Association's description of Syndrome X]</ref>:
* 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:
#aging,
#genetics and
#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]].<ref>{{cite journal | author=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 | title=A causal role for uric acid in fructose-induced metabolic syndrome | journal=Am J Phys Renal Phys | year=2006 | volume=290 | issue=3 | pages= F625–F631 | pmid=16234313 | doi=10.1152/ajprenal.00140.2005}}</ref><ref>{{cite journal | author=Hallfrisch J | title=Metabolic effects of dietary fructose | journal=FASEB J | year=1990 | volume=4 | issue=9 | pages= 2652–2660 | pmid=2189777}}</ref><ref>{{cite journal | author=Reiser S, Powell AS, Scholfield DJ, Panda P, Ellwood KC, Canary JJ | title=Blood lipids, lipoproteins, apoproteins, and uric acid in men fed diets containing fructose or high-amylose cornstarch | journal= Am J Clin Nutr | year=1989 | volume=49 | issue=5 | pages= 832–839 | pmid=2497634}}</ref>
==Pathophysiology==
Commonly there is development of [[visceral fat]] after which the [[adipocyte]]s (fat [[Cell (biology)|cell]]s) of the visceral fat increase [[blood plasma|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 [[cytokine]]s, but possibly to trigger cell signalling by interaction with a TNFα [[Receptor (biochemistry)|receptor]] that may lead to insulin resistance {{Fact|date=August 2007}}. 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 [[triglyceride]]s, which induced [[visceral]] fat and ultimately resulted in insulin resistance <ref>{{cite journal | author=Fukuchi S, Hamaguchi K, Seike M, Himeno K, Sakata T, Yoshimatsu H. | title=Role of Fatty Acid Composition in the Development of Metabolic Disorders in Sucrose-Induced Obese Rats | journal=Exp Biol Med | year=2004 | volume=229 | issue=6 | pages= 486–493 | url=http://www.ebmonline.org/cgi/content/full/229/6/486 | pmid=15169967}}</ref>. 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),<ref>{{cite journal |author=Lakka TA, Laaksonen DE |title=Physical activity in prevention and treatment of the metabolic syndrome |journal=Applied physiology, nutrition, and metabolism = Physiologie appliquée, nutrition et métabolisme |volume=32 |issue=1 |pages=76–88 |year=2007 |pmid=17332786 |doi=10.1139/h06-113}}</ref> and a healthy, reduced calorie diet.<ref>{{cite journal |author=Feldeisen SE, Tucker KL |title=Nutritional strategies in the prevention and treatment of metabolic syndrome |journal=Appl Physiol Nutr Metab |volume=32 |issue=1 |pages=46–60 |year=2007 |pmid=17332784 |doi=10.1139/h06-101}}</ref> 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.<ref name="katzmaryk" /> The [[International Obesity Taskforce]] states that interventions on a sociopolitical level are required to reduce development of the metabolic syndrome in populations.<ref>{{cite journal |author=James PT, Rigby N, Leach R |title=The obesity epidemic, metabolic syndrome and future prevention strategies |journal=Eur J Cardiovasc Prev Rehabil |volume=11 |issue=1 |pages=3–8 |year=2004 |pmid=15167200| doi = 10.1097/01.hjr.0000114707.27531.48 <!--Retrieved from CrossRef by DOI bot-->}}</ref>
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.<ref>{{cite journal |last=Elwood |first=PC |coauthors=Pickering JE, Fehily AM |year=2007 |title=Milk and dairy consumption, diabetes and the metabolic syndrome: the Caerphilly prospective study |journal= J Epidemiol Community Health |volume=61 |issue=8 |pages=695–698 |pmid=17630368 |url=http://jech.bmj.com/cgi/content/abstract/61/8/695 |doi=10.1136/jech.2006.053157}}</ref> Other studies both support and dispute the authors' findings.<ref>{{cite journal |author=Snijder MB, van der Heijden AA, van Dam RM, ''et al'' |title=Is higher dairy consumption associated with lower body weight and fewer metabolic disturbances? The Hoorn Study |journal=Am. J. Clin. Nutr. |volume=85 |issue=4 |pages=989–95 |year=2007 |pmid=17413097 |doi=}}</ref>
The most obvious method of prevention is undoubtedly to reduce the amount of carbohydrates, specifically fast digesting starches and sugars.
== 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. [[Diuretic]]s and [[ACE inhibitor]]s may be used to treat [[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 [[thiazolidinedione]]s, 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.<ref name="katzmaryk">{{cite journal
| last = Katzmaryk,
| first = Peter T
| coauthors = Leon, Arthur S.; Wilmore, Jack H.; Skinner, James S.; Rao, D. C.; Rankinen, Tuomo; Bouchard, Claude
| title = Targeting the Metabolic Syndrome with Exercise: Evidence from the HERITAGE Family Study.
| journal = Med. Sci. Sports Exerc
| volume = 35
| issue = 10
| pages = 1703–1709
| date = [[October 2003]]
| url = http://www.ms-se.com/pt/re/msse/abstract.00005768-200310000-00013.htm
| accessdate = 2007-06-24
| doi = 10.1249/01.MSS.0000089337.73244.9B }}
</ref>
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.<ref>Joslin EP. The prevention of diabetes mellitus. ''JAMA'' 1921;76:79–84.</ref><ref>Kylin E. [Studies of the hypertension-hyperglycemia-hyperuricemia syndrome] (German). ''Zentralbl Inn Med'' 1923;44: 105-27.</ref>
* 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.<ref>Vague J. La diffférenciacion sexuelle, facteur déterminant des formes de l'obésité. Presse Med 1947;30:339-40.</ref>
* 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.<ref>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.<!--No PMID--></ref>
* 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.<ref>Haller H. [Epidemiology and associated risk factors of hyperlipoproteinemia] (German). ''Z Gesamte Inn Med'' 1977;32(8):124-8. PMID 883354.</ref>
* The same year, Singer used the term for associations of obesity, gout, diabetes mellitus, and hypertension with hyperlipoprotenemia.<ref>Singer P. [Diagnosis of primary hyperlipoproteinemias] (German). ''Z Gesamte Inn Med'' 1977;32(9):129-33. PMID 906591.</ref>
* 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.<ref>Phillips GB. Sex hormones, risk factors and cardiovascular disease. ''Am J Med'' 1978;65:7-11. PMID 356599.</ref><ref>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.</ref>
* 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.<ref>Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 1988;37:1595-607. PMID 3056758.</ref>
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).
==Controversy==
The clinical value of the metabolic syndrome has recently come under fire. It is asserted that different sets of conflicting and incomplete diagnostic criteria are in existence, and that diagnosis of the metabolic syndrome has a negligible association with the risk of heart disease.<ref>{{cite journal
|title=Metabolic syndrome—what is the clinical usefulness?
|author=Richard Kahn
|journal=Lancet
|year=2008
|volume=371
|pages=1892–1893
|doi=10.1016/S0140-6736(08)60731-X}}</ref>
These concerns have led to the [[American Diabetes Association]] and the [[European Association for the Study of Diabetes]] to issue a joint statement identifying eight major concerns on the clinical utility of the metabolic syndrome.<ref>{{cite journal
|author=Kahn R, Buse J, Ferrannini E, Stern M
|title=The metabolic syndrome: time for a critical appraisal. Joint statement from the American Diabetes Association and the European Association for the Study of Diabetes
|journal=Diabetes Care
|year=2005
|volume=28
|pages=2289–2304
|pmid=16123508
|doi=10.2337/diacare.28.9.2289}}</ref>
It is not contested that cardiovascular risk factors tend to cluster together, but what is contested is the assertion that the metabolic syndrome is anything more than the sum of its constituent parts.
==See also==
* [[Hyperinsulinemia]]
* [[Insulin resistance]]
* [[Chronic Somogyi rebound]]
==References==
{{Reflist|2}}
[[Category:Diabetes]]
[[Category:Endocrinology]]
[[Category:Medical conditions related to obesity]]
[[Category:Syndromes]]
{{link FA|it}}
[[de:Metabolisches Syndrom]]
[[es:Síndrome metabólico]]
[[ko:대사 증후군]]
[[it:Sindrome metabolica]]
[[nl:Metabool syndroom]]
[[ja:メタボリックシンドローム]]
[[pl:Zespół metaboliczny]]
[[pt:Síndrome metabólica]]
[[ru:Метаболический синдром]]
[[fi:Metabolinen oireyhtymä]]
[[sv:Metabolt syndrom]]
[[zh:代謝症候群]]