Editing Metabolic syndrome

{{Infobox medical condition (new)
| name =
| synonyms = Dysmetabolic syndrome X
| image = Obesity6.JPG
| caption = A man with marked central obesity, a hallmark of metabolic syndrome. His weight is 182 kg (400 lbs), height 185 cm (6 ft 1 in), and [[body mass index]] (BMI) 53 (normal 18.5 to 24.9).
| field = [[Endocrinology]]
| symptoms = [[Obesity]]
| complications =
| onset =
| duration =
| types =
| causes =
| risks =
| diagnosis =
| differential = [[Insulin resistance]], [[prediabetes]], [[hyperuricemia]], [[obesity]], [[nonalcoholic fatty liver disease]], [[polycystic ovarian syndrome]], [[erectile dysfunction]], [[acanthosis nigricans]]
| prevention =
| treatment =
| medication =
| prognosis =
| frequency =
| deaths =
}}
{{Human body weight}}

'''Metabolic syndrome''' is a clustering of at least three of the following five medical conditions: [[abdominal obesity]], [[hypertension|high blood pressure]], [[hyperglycemia|high blood sugar]], [[Hypertriglyceridemia|high serum triglycerides]], and low serum [[high-density lipoprotein]] (HDL).

Metabolic syndrome is associated with the risk of developing [[cardiovascular disease]] and [[Diabetes mellitus type 2|type 2 diabetes]].<ref name="Mayo-metabolic">{{Cite web |title=Metabolic syndrome |url=https://www.mayoclinic.org/diseases-conditions/metabolic-syndrome/symptoms-causes/syc-20351916 |access-date=10 Sep 2020 |publisher=Mayo Clinic}}</ref> In the U.S., about 25% of the adult population has metabolic syndrome, a proportion increasing with age, particularly among racial and ethnic minorities.<ref name="Falkner-2014">{{Cite journal |vauthors=Falkner B, Cossrow ND |date=July 2014 |title=Prevalence of metabolic syndrome and obesity-associated hypertension in the racial ethnic minorities of the United States |journal=Current Hypertension Reports |volume=16 |issue=7 |pages=449 |doi=10.1007/s11906-014-0449-5 |pmc=4083846 |pmid=24819559}}</ref><ref name="pmid23810877">{{Cite journal |vauthors=Beltrán-Sánchez H, Harhay MO, Harhay MM, McElligott S |date=August 2013 |title=Prevalence and trends of metabolic syndrome in the adult U.S. population, 1999–2010 |journal=Journal of the American College of Cardiology |volume=62 |issue=8 |pages=697–703 |doi=10.1016/j.jacc.2013.05.064 |pmc=3756561 |pmid=23810877}}</ref>

[[Insulin resistance]], metabolic syndrome, and [[prediabetes]] are closely related to one another and have overlapping aspects. The [[syndrome]] is thought to be caused by an underlying disorder of energy utilization and storage, but the cause of the syndrome is an area of ongoing [[medical research]]. Researchers debate whether a diagnosis of metabolic syndrome implies differential treatment or increases risk of [[cardiovascular disease]] beyond what is suggested by the sum of its individual components.<ref name="Anagnostis2023">{{Cite journal |last=Anagnostis |first=Panagiotis |date=November 30, 2023 |title=Metabolic Syndrome |url=https://bestpractice.bmj.com/topics/en-us/212 |journal=BMJ Best Practice |access-date=30 December 2023}}</ref>

== Signs and symptoms ==
The key sign of metabolic syndrome is [[central obesity]], also known as visceral, male-pattern or apple-shaped adiposity. It is characterized by [[adipose tissue]] accumulation predominantly around the waist and trunk.<ref>{{Cite web |date=15 January 2019 |title=Metabolic Syndrome |url=http://www.diabetes.co.uk/diabetes-and-metabolic-syndrome.html |website=Diabetes.co.uk}}</ref> Other signs of metabolic syndrome include high blood pressure, decreased fasting serum HDL cholesterol, elevated fasting serum [[triglyceride]] level, [[impaired fasting glucose]], insulin resistance, or prediabetes. Associated conditions include [[hyperuricemia]]; [[fatty liver]] (especially in concurrent [[obesity]]) progressing to [[nonalcoholic fatty liver disease]]; [[polycystic ovarian syndrome]] in women and [[erectile dysfunction]] in men; and [[acanthosis nigricans]].<ref>{{Cite journal |display-authors=6 |vauthors=Mendrick DL, Diehl AM, Topor LS, Dietert RR, Will Y, La Merrill MA, Bouret S, Varma V, Hastings KL, Schug TT, Emeigh Hart SG, Burleson FG |date=March 2018 |title=Metabolic Syndrome and Associated Diseases: From the Bench to the Clinic |journal=Toxicological Sciences |volume=162 |issue=1 |pages=36–42 |doi=10.1093/toxsci/kfx233 |pmc=6256950 |pmid=29106690}}</ref>

=== Neck circumference ===
Neck circumference has been used as a surrogate simple and reliable index to indicate upper-body subcutaneous fat accumulation. Neck circumference of more than {{cvt|40.25|cm}} for men and more than {{cvt|35.75|cm}} for women are considered high-risk for metabolic syndrome. Persons with large neck circumferences have a more-than-double risk of metabolic syndrome.<ref>{{Cite journal |last=Mohseni-Takalloo |first=Sahar |last2=Mozaffari-Khosravi |first2=Hassan |last3=Mohseni |first3=Hadis |last4=Mirzaei |first4=Masoud |last5=Hosseinzadeh |first5=Mahdieh |date=2023-06-13 |title=Evaluating Neck Circumference as an Independent Predictor of Metabolic Syndrome and Its Components Among Adults: A Population-Based Study |journal=Cureus |language=en |volume=15 |issue=6 |pages=e40379 |doi=10.7759/cureus.40379 |issn=2168-8184 |pmc=10344419 |pmid=37456431 |doi-access=free}}</ref> In adults with overweight/obesity, clinically significant weight loss may protect against COVID-19<ref>{{Cite journal |last=Shyam |first=Sangeetha |last2=García-Gavilán |first2=Jesús Francisco |last3=Paz-Graniel |first3=Indira |last4=Gaforio |first4=José J. |last5=Martínez-González |first5=Miguel Ángel |last6=Corella |first6=Dolores |last7=Martínez |first7=J. Alfredo |last8=Alonso-Gómez |first8=Ángel M. |last9=Wärnberg |first9=Julia |last10=Vioque |first10=Jesús |last11=Romaguera |first11=Dora |last12=López-Miranda |first12=José |last13=Estruch |first13=Ramon |last14=Tinahones |first14=Francisco J. |last15=Lapetra |first15=José |date=2023-10-13 |title=Association of adiposity and its changes over time with COVID-19 risk in older adults with overweight/obesity and metabolic syndrome: a longitudinal evaluation in the PREDIMED-Plus cohort |journal=BMC Medicine |language=en |volume=21 |issue=1 |page=390 |doi=10.1186/s12916-023-03079-z |issn=1741-7015 |pmc=10576302 |pmid=37833678 |doi-access=free}}</ref> and neck circumference has been associated with the risk of being mechanically ventilated in COVID-19 patients, with a 26% increased risk for each centimeter increase in neck circumference.<ref>{{Cite journal |last=Di Bella |first=Stefano |last2=Cesareo |first2=Roberto |last3=De Cristofaro |first3=Paolo |last4=Palermo |first4=Andrea |last5=Sanson |first5=Gianfranco |last6=Roman-Pognuz |first6=Erik |last7=Zerbato |first7=Verena |last8=Manfrini |first8=Silvia |last9=Giacomazzi |first9=Donatella |last10=Dal Bo |first10=Eugenia |last11=Sambataro |first11=Gianluca |last12=Macchini |first12=Elisabetta |last13=Quintavalle |first13=Francesco |last14=Campagna |first14=Giuseppe |last15=Masala |first15=Renato |date=2021 |title=Neck circumference as reliable predictor of mechanical ventilation support in adult inpatients with COVID-19: A multicentric prospective evaluation |journal=Diabetes/Metabolism Research and Reviews |language=en |volume=37 |issue=1 |pages=e3354 |doi=10.1002/dmrr.3354 |issn=1520-7552 |pmc=7300447 |pmid=32484298}}</ref> Moreover, hospitalized COVID-19 patients with a "large neck phenotype" on admission had a more than double risk of death.<ref>{{Cite journal |last=Di Bella |first=Stefano |last2=Zerbato |first2=Verena |last3=Sanson |first3=Gianfranco |last4=Roman-Pognuz |first4=Erik |last5=De Cristofaro |first5=Paolo |last6=Palermo |first6=Andrea |last7=Valentini |first7=Michael |last8=Gobbo |first8=Ylenia |last9=Jaracz |first9=Anna Wladyslawa |last10=Bozic Hrzica |first10=Elizabeta |last11=Bresani-Salvi |first11=Cristiane Campello |last12=Galindo |first12=Alexandre Bezerra |last13=Crovella |first13=Sergio |last14=Luzzati |first14=Roberto |date=2021-12-10 |title=Neck Circumference Predicts Mortality in Hospitalized COVID-19 Patients |journal=Infectious Disease Reports |language=en |volume=13 |issue=4 |pages=1053–60 |doi=10.3390/idr13040096 |issn=2036-7449 |pmc=8700782 |pmid=34940406 |doi-access=free}}</ref>

=== Complications ===
Metabolic syndrome can lead to several serious and chronic complications, including [[Type 2 diabetes|type-2 diabetes]], [[cardiovascular disease]]s, [[stroke]], [[kidney disease]] and [[Non-alcoholic fatty liver disease|nonalcoholic fatty liver disease.]]<ref>{{Cite web |title=Metabolic syndrome – Symptoms and causes |url=https://www.mayoclinic.org/diseases-conditions/metabolic-syndrome/symptoms-causes/syc-20351916 |access-date=2022-03-31 |website=Mayo Clinic |language=en}}</ref>

Furthermore, metabolic syndrome is associated with a significantly increased risk of surgical complications across most types of surgery in a 2023 systematic review and meta-analysis of over 13 million individuals.<ref>{{Cite journal |last=Norris |first=Philip |last2=Gow |first2=Jeff |last3=Arthur |first3=Thomas |last4=Conway |first4=Aaron |last5=Fleming |first5=Fergal J |last6=Ralph |first6=Nicholas |date=2 November 2023 |title=Metabolic syndrome and surgical complications: A systematic review and meta-analysis of 13 million individuals |journal=International Journal of Surgery |volume=110 |issue=1 |pages=541–53 |doi=10.1097/JS9.0000000000000834 |pmc=10793842 |pmid=37916943 |doi-access=free}}</ref>

==Causes==
The mechanisms of the complex pathways of metabolic syndrome are under investigation. The [[pathophysiology]] is very complex and has been only partially elucidated. Most people affected by the condition are older, obese, sedentary, and have a degree of insulin resistance. [[Stress (biology)|Stress]] can also be a contributing factor. The most important [[risk factors]] are diet (particularly sugar-sweetened beverage consumption),<ref name="PMID20693348">{{Cite journal |vauthors=Malik VS, Popkin BM, Bray GA, Després JP, Willett WC, Hu FB |date=November 2010 |title=Sugar-sweetened beverages and risk of metabolic syndrome and type 2 diabetes: a meta-analysis |journal=Diabetes Care |volume=33 |issue=11 |pages=2477–83 |doi=10.2337/dc10-1079 |pmc=2963518 |pmid=20693348}}</ref> genetics,<ref>{{Cite journal |vauthors=Pollex RL, Hegele RA |date=September 2006 |title=Genetic determinants of the metabolic syndrome |journal=Nature Clinical Practice Cardiovascular Medicine |volume=3 |issue=9 |pages=482–89 |doi=10.1038/ncpcardio0638 |pmid=16932765 |s2cid=24558150}}</ref><ref>{{Cite journal |vauthors=Poulsen P, Vaag A, Kyvik K, Beck-Nielsen H |date=May 2001 |title=Genetic versus environmental aetiology of the metabolic syndrome among male and female twins |journal=Diabetologia |volume=44 |issue=5 |pages=537–43 |doi=10.1007/s001250051659 |pmid=11380071 |s2cid=26582450 |doi-access=free}}</ref><ref name="Groop2000">{{Cite journal |vauthors=Groop L |date=March 2000 |title=Genetics of the metabolic syndrome |journal=The British Journal of Nutrition |volume=83 |issue=Suppl 1 |pages=S39–S48 |doi=10.1017/S0007114500000945 |pmid=10889791 |s2cid=8974554 |doi-access=free}}</ref><ref name="Bouchard1995">{{Cite journal |vauthors=Bouchard C |date=May 1995 |title=Genetics and the metabolic syndrome |journal=International Journal of Obesity and Related Metabolic Disorders |volume=19 |issue=Suppl 1 |pages=S52–59 |pmid=7550538}}</ref> aging, sedentary behavior<ref name="PMID22514690">{{Cite journal |vauthors=Edwardson CL, Gorely T, Davies MJ, Gray LJ, Khunti K, Wilmot EG, Yates T, Biddle SJ |year=2012 |title=Association of sedentary behaviour with metabolic syndrome: a meta-analysis |journal=PLOS ONE |volume=7 |issue=4 |pages=e34916 |bibcode=2012PLoSO...734916E |doi=10.1371/journal.pone.0034916 |pmc=3325927 |pmid=22514690 |doi-access=free}}</ref> or low physical activity,<ref name="katzmaryk">{{Cite journal |vauthors=Katzmarzyk PT, Leon AS, Wilmore JH, Skinner JS, Rao DC, Rankinen T, Bouchard C |date=October 2003 |title=Targeting the metabolic syndrome with exercise: evidence from the HERITAGE Family Study |journal=Medicine and Science in Sports and Exercise |volume=35 |issue=10 |pages=1703–09 |doi=10.1249/01.MSS.0000089337.73244.9B |pmid=14523308 |s2cid=25598917 |doi-access=free}}</ref><ref>{{Cite journal |vauthors=He D, Xi B, Xue J, Huai P, Zhang M, Li J |date=June 2014 |title=Association between leisure time physical activity and metabolic syndrome: a meta-analysis of prospective cohort studies |journal=Endocrine |volume=46 |issue=2 |pages=231–40 |doi=10.1007/s12020-013-0110-0 |pmid=24287790 |s2cid=5271746}}</ref> disrupted [[chronobiology]]/sleep,<ref name="PMID23890470">{{Cite journal |vauthors=Xi B, He D, Zhang M, Xue J, Zhou D |date=August 2014 |title=Short sleep duration predicts risk of metabolic syndrome: a systematic review and meta-analysis |journal=Sleep Medicine Reviews |volume=18 |issue=4 |pages=293–97 |doi=10.1016/j.smrv.2013.06.001 |pmid=23890470}}</ref> mood disorders/psychotropic medication use,<ref name="PMID24262678">{{Cite journal |vauthors=Vancampfort D, Correll CU, Wampers M, Sienaert P, Mitchell AJ, De Herdt A, Probst M, Scheewe TW, De Hert M |date=July 2014 |title=Metabolic syndrome and metabolic abnormalities in patients with major depressive disorder: a meta-analysis of prevalences and moderating variables |url=https://lirias.kuleuven.be/handle/123456789/398044 |journal=Psychological Medicine |volume=44 |issue=10 |pages=2017–28 |doi=10.1017/S0033291713002778 |pmid=24262678 |s2cid=206253750}}</ref><ref name="PMID23361837">{{Cite journal |vauthors=Vancampfort D, Vansteelandt K, Correll CU, Mitchell AJ, De Herdt A, Sienaert P, Probst M, De Hert M |date=March 2013 |title=Metabolic syndrome and metabolic abnormalities in bipolar disorder: a meta-analysis of prevalence rates and moderators |journal=The American Journal of Psychiatry |volume=170 |issue=3 |pages=265–74 |doi=10.1176/appi.ajp.2012.12050620 |pmid=23361837}}</ref> and excessive alcohol use.<ref name="PMID24315622">{{Cite journal |vauthors=Sun K, Ren M, Liu D, Wang C, Yang C, Yan L |date=August 2014 |title=Alcohol consumption and risk of metabolic syndrome: a meta-analysis of prospective studies |journal=Clinical Nutrition |volume=33 |issue=4 |pages=596–602 |doi=10.1016/j.clnu.2013.10.003 |pmid=24315622}}</ref> The pathogenic role played in the syndrome by the excessive expansion of adipose tissue occurring under sustained [[overeating]], and its resulting [[lipotoxicity]] was reviewed by [[Antonio Vidal-Puig|Vidal-Puig]].<ref>{{Cite journal |vauthors=Vidal-Puig A |date=2013 |title=Adipose tissue expandability, lipotoxicity and the metabolic syndrome |journal=Endocrinologia y Nutricion |volume=60 |issue=Suppl 1 |pages=39–43 |doi=10.1016/s1575-0922(13)70026-3 |pmid=24490226}}</ref>

Recent studies have highlighted the global prevalence of metabolic syndrome, driven by the rise in obesity and type 2 diabetes. The World Health Organization (WHO) and other major health organizations define metabolic syndrome with criteria that include central obesity, insulin resistance, hypertension, and dyslipidemia. As of 2015, metabolic syndrome affects approximately 25% of the global population, with rates significantly higher in urban areas due to increased consumption of high-calorie, low-nutrient diets and decreased physical activity. This condition is associated with a threefold increase in the risk of type 2 diabetes and cardiovascular disease, accounting for a substantial burden of non-communicable diseases globally (Saklayen, 2018).<ref>{{Cite journal |last=Saklayen |first=M.G. |date=2018 |title=The Global Epidemic of the Metabolic Syndrome |journal=Current Hypertension Reports |volume=20 |issue=2 |pages=12 |doi=10.1007/s11906-018-0812-z |pmc=5866840 |pmid=29480368}}</ref>

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. Markers of systemic [[inflammation]], including [[C-reactive protein]], are often increased, as are [[fibrinogen]], [[interleukin 6]], [[tumor necrosis factor-alpha]]&nbsp;(TNF-α), and others. Some have pointed to a variety of causes, including increased [[uric acid]] levels caused by dietary [[fructose]].<ref>{{Cite journal |vauthors=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 |date=March 2006 |title=A causal role for uric acid in fructose-induced metabolic syndrome |journal=American Journal of Physiology. Renal Physiology |volume=290 |issue=3 |pages=F625–31 |doi=10.1152/ajprenal.00140.2005 |pmid=16234313}}</ref><ref>{{Cite journal |vauthors=Hallfrisch J |date=June 1990 |title=Metabolic effects of dietary fructose |journal=FASEB Journal |volume=4 |issue=9 |pages=2652–60 |doi=10.1096/fasebj.4.9.2189777 |pmid=2189777 |s2cid=23659634 |doi-access=free}}</ref><ref>{{Cite journal |vauthors=Reiser S, Powell AS, Scholfield DJ, Panda P, Ellwood KC, Canary JJ |date=May 1989 |title=Blood lipids, lipoproteins, apoproteins, and uric acid in men fed diets containing fructose or high-amylose cornstarch |journal=The American Journal of Clinical Nutrition |volume=49 |issue=5 |pages=832–39 |doi=10.1093/ajcn/49.5.832 |pmid=2497634 |doi-access=free}}</ref>

Research shows that Western diet habits are a factor in the development of metabolic syndrome, with high consumption of food that is not biochemically suited to humans.<ref name="PMID22351884">{{Cite journal |vauthors=Bremer AA, Mietus-Snyder M, Lustig RH |date=March 2012 |title=Toward a unifying hypothesis of metabolic syndrome |journal=Pediatrics |volume=129 |issue=3 |pages=557–70 |doi=10.1542/peds.2011-2912 |pmc=3289531 |pmid=22351884}}</ref>{{page needed|date=September 2020}} Weight gain is associated with metabolic syndrome. Rather than total adiposity, the core clinical component of the syndrome is visceral and/or ectopic fat (i.e., fat in organs not designed for fat storage) whereas the principal metabolic abnormality is insulin resistance.<ref>{{Cite journal |vauthors=Ali ES, Hua J, Wilson CH, Tallis GA, Zhou FH, Rychkov GY, Barritt GJ |date=September 2016 |title=The glucagon-like peptide-1 analogue exendin-4 reverses impaired intracellular Ca(2+) signalling in steatotic hepatocytes |journal=Biochimica et Biophysica Acta (BBA) - Molecular Cell Research |volume=1863 |issue=9 |pages=2135–46 |doi=10.1016/j.bbamcr.2016.05.006 |pmid=27178543}}</ref> The continuous provision of energy via dietary [[Carbohydrate metabolism|carbohydrate]], [[Lipid metabolism|lipid]], and [[Protein metabolism|protein]] fuels, unmatched by physical activity/energy demand, creates a backlog of the products of [[Oxidative phosphorylation|mitochondrial oxidation]], a process associated with progressive mitochondrial dysfunction and insulin resistance.<ref>{{Cite journal |last=Bremer |first=A. A. |last2=Mietus-Snyder |first2=M. |last3=Lustig |first3=R. H. |date=2012 |title=Toward a Unifying Hypothesis of Metabolic Syndrome |url=https://pmc.ncbi.nlm.nih.gov/articles/PMC3289531/ |journal=Pediatrics |volume=129 |issue=3 |pages=557–570 |doi=10.1542/peds.2011-2912 |via=PubMed Central|pmc=3289531 }}</ref>

===Stress===
Recent research indicates prolonged [[chronic stress]] can contribute to metabolic syndrome by disrupting the hormonal balance of the [[hypothalamic-pituitary-adrenal axis]] (HPA-axis).<ref name="Gohill">{{Cite journal |vauthors=Gohil BC, Rosenblum LA, Coplan JD, Kral JG |date=July 2001 |title=Hypothalamic-pituitary-adrenal axis function and the metabolic syndrome X of obesity |journal=CNS Spectrums |volume=6 |issue=7 |pages=581–86, 589 |doi=10.1017/s1092852900002121 |pmid=15573024 |s2cid=22734016}}</ref> A dysfunctional HPA-axis causes high [[cortisol]] levels to circulate, which results in raising [[glucose]] and [[insulin]] levels, which in turn cause insulin-mediated effects on adipose tissue, ultimately promoting [[visceral adiposity]], insulin resistance, dyslipidemia and hypertension, with direct effects on the bone, causing "low turnover" [[osteoporosis]].<ref name="tsigos">{{Cite journal |vauthors=Tsigos C, Chrousos GP |date=October 2002 |title=Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress |url=https://zenodo.org/record/1259653 |journal=Journal of Psychosomatic Research |volume=53 |issue=4 |pages=865–71 |doi=10.1016/S0022-3999(02)00429-4 |pmid=12377295}}</ref> HPA-axis dysfunction may explain the reported risk indication of abdominal obesity to [[cardiovascular disease]] (CVD), type 2 diabetes and [[stroke]].<ref name="rosmond">{{Cite journal |vauthors=Rosmond R, Björntorp P |date=February 2000 |title=The hypothalamic-pituitary-adrenal axis activity as a predictor of cardiovascular disease, type 2 diabetes and stroke |journal=Journal of Internal Medicine |volume=247 |issue=2 |pages=188–97 |doi=10.1046/j.1365-2796.2000.00603.x |pmid=10692081 |s2cid=20336259 |doi-access=free}}</ref> [[Psychosocial]] stress is also linked to heart disease.<ref name="brunner">{{Cite journal |vauthors=Brunner EJ, Hemingway H, Walker BR, Page M, Clarke P, Juneja M, Shipley MJ, Kumari M, Andrew R, Seckl JR, Papadopoulos A, Checkley S, Rumley A, Lowe GD, Stansfeld SA, Marmot MG |date=November 2002 |title=Adrenocortical, autonomic, and inflammatory causes of the metabolic syndrome: nested case-control study |journal=Circulation |volume=106 |issue=21 |pages=2659–65 |doi=10.1161/01.cir.0000038364.26310.bd |pmid=12438290 |s2cid=5992769 |doi-access=free}}</ref>

===Obesity===
Central obesity is a key feature of the syndrome, as both a sign and a cause, in that the increasing adiposity often reflected in high [[waist circumference]] may both result from and contribute to insulin resistance. However, despite the importance of obesity, affected people who are of normal weight may also be insulin-resistant and have the syndrome.<ref name="isbn0-07-147692-X">{{Cite book |last=Fauci, Anthony S. |title=Harrison's principles of internal medicine |publisher=McGraw-Hill Medical |year=2008 |isbn=978-0-07-147692-8}}{{page needed|date=October 2017}}</ref>

===Sedentary lifestyle===
Physical inactivity is a predictor of CVD events and related [[Death|mortality]]. Many components of metabolic syndrome are associated with a [[sedentary lifestyle]], including increased adipose tissue (predominantly central); reduced HDL cholesterol; and a trend toward increased triglycerides, blood pressure, and glucose in the genetically susceptible. Compared with individuals who watched television or videos or used their computers for less than one hour daily, those who carried out these behaviors for greater than four hours daily have a twofold increased risk of metabolic syndrome.<ref name="isbn0-07-147692-X" />

===Aging===
Metabolic syndrome affects 60% of the U.S. population older than age 50. With respect to that demographic, the percentage of women having the syndrome is higher than that of men. The age dependency of the syndrome's prevalence is seen in most populations around the world.<ref name="isbn0-07-147692-X" />

===Diabetes mellitus type 2===
{{main|Diabetes mellitus|Diabetes mellitus type 2}}

The metabolic syndrome quintuples the risk of type 2 diabetes mellitus. Type 2 diabetes is considered a [[complication (medicine)|complication]] of metabolic syndrome.<ref name="Mayo-metabolic" /> In people with impaired glucose tolerance or impaired fasting glucose, presence of metabolic syndrome doubles the risk of developing type 2 diabetes.<ref name="PMID22895669">{{Cite journal |vauthors=Goldberg RB, Mather K |date=September 2012 |title=Targeting the consequences of the metabolic syndrome in the Diabetes Prevention Program |journal=Arteriosclerosis, Thrombosis, and Vascular Biology |volume=32 |issue=9 |pages=2077–90 |doi=10.1161/ATVBAHA.111.241893 |pmc=3901161 |pmid=22895669}}</ref> It is likely that prediabetes and metabolic syndrome denote the same disorder, defining it by the different sets of biological markers.{{citation needed|date=June 2022}}

The presence of metabolic syndrome is associated with a higher prevalence of CVD than found in people with type 2 diabetes or [[impaired glucose tolerance]] without the syndrome.<ref name="isbn0-07-147692-X" /> [[Adiponectin#Hypoadiponectinemia|Hypoadiponectinemia]] has been shown to increase insulin resistance<ref name="pmid17495599">{{Cite journal |vauthors=Lara-Castro C, Fu Y, Chung BH, Garvey WT |date=June 2007 |title=Adiponectin and the metabolic syndrome: mechanisms mediating risk for metabolic and cardiovascular disease |journal=Current Opinion in Lipidology |volume=18 |issue=3 |pages=263–70 |doi=10.1097/MOL.0b013e32814a645f |pmid=17495599 |s2cid=20799218}}</ref> and is considered to be a risk factor for developing metabolic syndrome.<ref name="pmid19258676">{{Cite journal |vauthors=Renaldi O, Pramono B, Sinorita H, Purnomo LB, Asdie RH, Asdie AH |date=January 2009 |title=Hypoadiponectinemia: a risk factor for metabolic syndrome |journal=Acta Medica Indonesiana |volume=41 |issue=1 |pages=20–24 |pmid=19258676}}</ref>

===Coronary heart disease===
The approximate prevalence of the metabolic syndrome in people with [[coronary artery disease]] (CAD) is 50%, with a prevalence of 37% in people with premature coronary artery disease (age 45), particularly in women. With appropriate [[Cardiopulmonary rehabilitation|cardiac rehabilitation]] and changes in lifestyle (e.g., nutrition, physical activity, weight reduction, and, in some cases, drugs), the prevalence of the syndrome can be reduced.<ref name="isbn0-07-147692-X" />

===Lipodystrophy===
[[Lipodystrophy|Lipodystrophic disorders]] in general are associated with metabolic syndrome. Both genetic (e.g., [[Berardinelli-Seip congenital lipodystrophy]], [[Dunnigan familial partial lipodystrophy]]) and acquired (e.g., [[HIV]]-related lipodystrophy in people treated with [[highly active antiretroviral therapy]]) forms of lipodystrophy may give rise to severe insulin resistance and many of metabolic syndrome's components.<ref name="isbn0-07-147692-X" />

===Rheumatic diseases===
There is research that associates comorbidity with rheumatic diseases. Both [[psoriasis]] and [[psoriatic arthritis]] have been found to be associated with metabolic syndrome.<ref>{{Cite journal |vauthors=Quilon III A, Brent L |year=2010 |title=The primary care physician's guide to inflammatory arthritis: diagnosis |url=http://www.musculoskeletalnetwork.com/display/article/1145622/1579185 |journal=The Journal of Musculoskeletal Medicine |volume=27 |pages=223–31}}</ref>

===Chronic obstructive pulmonary disease===
Metabolic syndrome is seen to be a comorbidity in up to 50 percent of those with [[chronic obstructive pulmonary disease]] (COPD). It may pre-exist or may be a consequence of the lung pathology of COPD.<ref name="Chan">{{Cite journal |vauthors=Chan SM, Selemidis S, Bozinovski S, Vlahos R |date=June 2019 |title=Pathobiological mechanisms underlying metabolic syndrome (MetS) in chronic obstructive pulmonary disease (COPD): clinical significance and therapeutic strategies |journal=Pharmacol Ther |volume=198 |pages=160–88 |doi=10.1016/j.pharmthera.2019.02.013 |pmc=7112632 |pmid=30822464}}</ref>

==Pathophysiology==
It is common for there to be a development of [[visceral fat]], after which the [[adipocyte]]s (fat cells) of the visceral fat increase [[blood plasma|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 [[cytokine]]s and also possibly trigger cell signaling by interaction with a [[TNF receptor superfamily|TNF-α receptor]] that may lead to insulin resistance.<ref>{{Cite journal |vauthors=Hotamisligil GS |date=June 1999 |title=The role of TNFalpha and TNF receptors in obesity and insulin resistance |journal=Journal of Internal Medicine |volume=245 |issue=6 |pages=621–25 |doi=10.1046/j.1365-2796.1999.00490.x |pmid=10395191 |s2cid=58332116 |doi-access=free}}</ref> 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.<ref>Whitney, Ellie and Ralfes, R. Sharon. 2011. ''Understanding Nutrition''. [[Wadsworth Cengage Learning]]: Belmont, CA</ref>

The involvement of the [[endocannabinoid system]] in the development of metabolic syndrome is indisputable.<ref name="ECS - metabolic disorders" /><ref name="ECS - MS" /><ref name="AA and endocannabinoids" /> Endocannabinoid overproduction may induce [[reward system]] dysfunction<ref name="ECS - MS">{{Cite journal |author-link3=Alexandros Makriyannis |vauthors=Vemuri VK, Janero DR, Makriyannis A |date=March 2008 |title=Pharmacotherapeutic targeting of the endocannabinoid signaling system: drugs for obesity and the metabolic syndrome |journal=Physiology & Behavior |volume=93 |issue=4–5 |pages=671–86 |doi=10.1016/j.physbeh.2007.11.012 |pmc=3681125 |pmid=18155257 |quote=The etiology of many appetitive disorders is characterized by a pathogenic component of reward-supported craving, be it for substances of abuse (including alcohol and nicotine) or food. Such maladies affect large numbers of people as prevalent socioeconomic and healthcare burdens. Yet in most instances drugs for their safe and effective pharmacotherapeutic management are lacking despite the attendant medical needs, collateral adverse physical and psychological effects, and enormous global market potential. The endocannabinoid signaling system plays a critical role in motivational homeostasis as a conduit for reward stimuli and a positive modulator of brain reward circuits. Endocannabinoid-system hyperactivity through CB1 receptor transmission is considered contributory to a range of appetitive disorders and, hence, is a major focus of contemporary pharmaceutical research.}}</ref> and cause [[executive dysfunction]]s (e.g., impaired delay discounting), in turn perpetuating unhealthy behaviors.{{medical citation needed|date=April 2016}} The brain is crucial in development of metabolic syndrome, modulating peripheral carbohydrate and lipid metabolism.<ref name="ECS - metabolic disorders">{{Cite book |title=Endocannabinoids |vauthors=Gatta-Cherifi B, Cota D |year=2015 |isbn=978-3-319-20824-4 |series=Handbook of Experimental Pharmacology |volume=231 |pages=367–91 |chapter=Endocannabinoids and Metabolic Disorders |doi=10.1007/978-3-319-20825-1_13 |pmid=26408168 |quote=The endocannabinoid system (ECS) is known to exert regulatory control on essentially every aspect related to the search for, and the intake, metabolism and storage of calories, and consequently it represents a potential pharmacotherapeutic target for obesity, diabetes and eating disorders.&nbsp;... recent research in animals and humans has provided new knowledge on the mechanisms of actions of the ECS in the regulation of eating behavior, energy balance, and metabolism. In this review, we discuss these recent advances and how they may allow targeting the ECS in a more specific and selective manner for the future development of therapies against obesity, metabolic syndrome, and eating disorders.}}</ref><ref name="ECS - MS" />

Metabolic syndrome can be induced by overfeeding with sucrose or fructose, particularly concomitantly with high-fat diet.<ref>{{Cite journal |vauthors=Fukuchi S, Hamaguchi K, Seike M, Himeno K, Sakata T, Yoshimatsu H |date=June 2004 |title=Role of fatty acid composition in the development of metabolic disorders in sucrose-induced obese rats |journal=Experimental Biology and Medicine |volume=229 |issue=6 |pages=486–93 |doi=10.1177/153537020422900606 |pmid=15169967 |s2cid=20966659}}</ref> 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|date=April 2016}} 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]].<ref name="FAAH">{{Cite journal |vauthors=Di Marzo V, Fontana A, Cadas H, et al. |date=Dec 1994 |title=Formation and inactivation of endogenous cannabinoid anandamide in central neurons |url=http://www.escholarship.org/uc/item/0kh020xm |journal=Nature |type=Submitted manuscript |volume=372 |issue=6507 |pages=686–91 |bibcode=1994Natur.372..686D |doi=10.1038/372686a0 |pmid=7990962 |s2cid=4341716}}</ref><ref name="AA and endocannabinoids">{{Cite journal |vauthors=Turcotte C, Chouinard F, Lefebvre JS, Flamand N |date=June 2015 |title=Regulation of inflammation by cannabinoids, the endocannabinoids 2-arachidonoyl-glycerol and arachidonoyl-ethanolamide, and their metabolites |journal=Journal of Leukocyte Biology |volume=97 |issue=6 |pages=1049–70 |doi=10.1189/jlb.3RU0115-021R |pmid=25877930 |s2cid=206999921}}</ref> Anandamide can also be produced from [[N-Acylphosphatidylethanolamine|''N''-acylphosphatidylethanolamine]] via several pathways.<ref name="AA and endocannabinoids" /> Anandamide and 2-AG can also be hydrolized into arachidonic acid, potentially leading to increased [[eicosanoid]] synthesis.<ref name="AA and endocannabinoids" />

== Diagnosis ==

===NCEP===
As of 2023, the U.S. [[National Cholesterol Education Program]] Adult Treatment Panel III (2001) continues to be the most widely used clinical definition.<ref name="Anagnostis2023" /> It requires at least three of the following:<ref>{{Cite journal |last=Expert Panel On Detection |first=Evaluation |date=May 2001 |title=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 |journal=JAMA |volume=285 |issue=19 |pages=2486–97 |doi=10.1001/jama.285.19.2486 |pmid=11368702}}</ref>
* Central obesity: waist circumference ≥ 102&nbsp;cm or 40&nbsp;inches (male), ≥ 88&nbsp;cm or 35&nbsp;inches(female)
* Dyslipidemia: TG ≥ 1.7&nbsp;mmol/L (150&nbsp;mg/dL)
* Dyslipidemia: HDL-C < 40&nbsp;mg/dL (male), < 50&nbsp;mg/dL (female)
* Blood pressure ≥ 130/85 mmHg (or treated for hypertension)
* Fasting plasma glucose ≥ 6.1&nbsp;mmol/L (110&nbsp;mg/dL)

===2009 Interim Joint Statement===
The [[International Diabetes Federation]] Task Force on Epidemiology and Prevention; the [[National Heart, Lung, and Blood Institute]]; the [[American Heart Association]]; the [[World Heart Federation]]; the [[International Atherosclerosis Society]]; and the [[International Association for the Study of Obesity]] published an interim joint statement to harmonize the definition of the metabolic syndrome in 2009.<ref name="PMID19805654">{{Cite journal |vauthors=Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM, Smith SC |date=October 2009 |title=Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity |url=http://circ.ahajournals.org/content/circulationaha/120/16/1640.full.pdf |journal=Circulation |volume=120 |issue=16 |pages=1640–45 |doi=10.1161/CIRCULATIONAHA.109.192644 |pmid=19805654}}</ref> According to this statement, the criteria for clinical diagnosis of the
metabolic syndrome are three or more of the following:
* Elevated waist circumference with population- and country-specific definitions
* Elevated triglycerides (≥ 150&nbsp;mg/dL (1.7&nbsp;mmol/L))
* Reduced HDL-C (≤40&nbsp;mg/dL (1.0&nbsp;mmol/L) in males, ≤50&nbsp;mg/dL (1.3&nbsp;mmol/L) in females)
* Elevated blood pressure (systolic ≥130 and/or diastolic ≥85&nbsp;mm Hg)
* Elevated fasting glucose (≥100&nbsp;mg/dL (5.55&nbsp;mmol/L)<ref name="PMID19805654" />

This definition recognizes that the risk associated with a particular waist measurement will differ in different populations. However, for international comparisons and to facilitate the etiology, the organizations agree that it is critical that a commonly agreed-upon set of criteria be used worldwide, with agreed-upon cut points for different ethnic groups and sexes. There are many people in the world of mixed ethnicity, and in those cases, pragmatic decisions will have to be made. Therefore, an international criterion of overweight may be more appropriate than ethnic specific criteria of abdominal obesity for an anthropometric component of this syndrome which results from an excess lipid storage in adipose tissue, skeletal muscle and liver.<ref name="PMID19805654" />

The report notes that previous definitions of the metabolic syndrome by the International Diabetes Federation<ref name="idf.org">{{Cite report |url=https://www.idf.org/our-activities/advocacy-awareness/resources-and-tools/60:idfconsensus-worldwide-definitionof-the-metabolic-syndrome.html |title=IDF Consensus Worldwide Definition of the Metabolic Syndrome |date=2006 |publisher=International Diabetes Federation |location=Brussels, Belgium |archive-url=https://web.archive.org/web/20120916064300/http://www.idf.org/webdata/docs/IDF_Meta_def_final.pdf |archive-date=2012-09-16 |vauthors=Alberti G, Zimmet P, Shaw J |veditors=Grundy SM}}</ref> (IDF) and the revised [[National Cholesterol Education Program]] (NCEP) are very similar, and they identify individuals with a given set of symptoms as having metabolic syndrome. There are two differences, however: the IDF definition states that if [[body mass index]] (BMI) is greater than 30&nbsp;kg/m<sup>2</sup>, central obesity can be assumed, and waist circumference does not need to be measured.  However, this potentially excludes any subject without increased waist circumference if BMI is less than 30. Conversely, the NCEP definition indicates that metabolic syndrome can be diagnosed based on other criteria. Also, 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.{{citation needed|date=June 2022}}

===WHO===
The [[World Health Organization]] (1999)<ref>{{Cite web |year=1999 |title=Definition, Diagnosis, and Classification of Diabetes Mellitus and its Complications |url=http://whqlibdoc.who.int/hq/1999/who_ncd_ncs_99.2.pdf |url-status=dead |archive-url=https://web.archive.org/web/20140821000053/http://whqlibdoc.who.int/hq/1999/WHO_NCD_NCS_99.2.pdf |archive-date=21 August 2014 |access-date=25 March 2013 |publisher=World Health Organization |pages=32–33 |vauthors=Alberti KG, etal}}</ref>  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&nbsp;mmol/L  and HDL cholesterol ≤ 0.9&nbsp;mmol/L (male), ≤ 1.0&nbsp;mmol/L (female)
* Central obesity: waist:hip ratio > 0.90 (male); > 0.85 (female), or BMI > 30&nbsp;kg/m<sup>2</sup>
* [[Microalbuminuria]]: urinary albumin excretion ratio ≥ 20&nbsp;μg/min or albumin:creatinine ratio ≥ 30&nbsp;mg/g

===EGIR===
The [http://www.egir.org/load.php?menu=public&page=http://www.egir.org/activity.html European Group for the Study of Insulin Resistance] (1999) requires that subjects have insulin resistance (defined for purposes of clinical practivality as the top 25% of the fasting insulin values among nondiabetic individuals) AND two or more of the following:<ref name="BalkauCharlesEGIR">{{Cite journal |last=Balkau B, Charles MA |date=May 1999 |title=Comment on the provisional report from the WHO consultation. European Group for the Study of Insulin Resistance (EGIR) |journal=Diabet Med |volume=16 |issue=5 |pages=442–43 |doi=10.1046/j.1464-5491.1999.00059.x |pmid=10342346}}</ref>
* Central obesity: waist circumference ≥ 94&nbsp;cm or 37 inches (male), ≥ 80&nbsp;cm or 31.5 inches (female)
* Dyslipidemia: TG ≥ 2.0&nbsp;mmol/L (177&nbsp;mg/dL) and/or HDL-C < 1.0&nbsp;mmol/L (38.61&nbsp;mg/dL) or treated for dyslipidemia
* Blood pressure ≥ 140/90 mmHg or antihypertensive medication
* Fasting plasma glucose ≥ 6.1&nbsp;mmol/L (110&nbsp;mg/dL)

===Cardiometabolic index===
The Cardiometabolic index (CMI) is a tool used to calculate risk of type 2 diabetes, non-alcoholic fatty liver disease,<ref name="Khanmohammadi Tavolinejad Aminorroaya Rezaie 2022 pp. 1943–1973">{{Cite journal |last=Khanmohammadi |first=Shaghayegh |last2=Tavolinejad |first2=Hamed |last3=Aminorroaya |first3=Arya |last4=Rezaie |first4=Yasaman |last5=Ashraf |first5=Haleh |last6=Vasheghani-Farahani |first6=Ali |date=2022-08-30 |title=Association of lipid accumulation product with type 2 diabetes mellitus, hypertension, and mortality: a systematic review and meta-analysis |journal=Journal of Diabetes & Metabolic Disorders |publisher=Springer Science and Business Media LLC |volume=21 |issue=2 |pages=1943–73 |doi=10.1007/s40200-022-01114-z |issn=2251-6581 |pmc=9672205 |pmid=36404835 |s2cid=251912707}}</ref> and metabolic issues. It is based on calculations from waist-to-height ratio and triglycerides-to-HDL cholesterol ratio.<ref name="Pluta Dudzińska Lubkowska 2022 p=624">{{Cite journal |last=Pluta |first=Waldemar |last2=Dudzińska |first2=Wioleta |last3=Lubkowska |first3=Anna |date=2022-01-06 |title=Metabolic Obesity in People with Normal Body Weight (MONW) – Review of Diagnostic Criteria |journal=International Journal of Environmental Research and Public Health |publisher=MDPI AG |volume=19 |issue=2 |page=624 |doi=10.3390/ijerph19020624 |issn=1660-4601 |pmc=8776153 |pmid=35055447 |doi-access=free}}</ref>

CMI can also be used for finding connections between cardiovascular disease and erectile dysfunction.<ref name="Chen Shi Huang Li 2019 p=108585">{{Cite journal |last=Chen |first=Lei |last2=Shi |first2=Guang-rui |last3=Huang |first3=Dan-dan |last4=Li |first4=Yang |last5=Ma |first5=Chen-chao |last6=Shi |first6=Min |last7=Su |first7=Bin-xiao |last8=Shi |first8=Guang-jiang |year=2019 |title=Male sexual dysfunction: A review of literature on its pathological mechanisms, potential risk factors, and herbal drug intervention |journal=Biomedicine & Pharmacotherapy |publisher=Elsevier BV |volume=112 |page=108585 |doi=10.1016/j.biopha.2019.01.046 |issn=0753-3322 |pmid=30798136 |doi-access=free}}</ref> When following an anti inflammatory diet (low-glycemic carbohydrates, fruits, vegetables, fish, less red meat and processed foods) the markers may drop resulting in a significant reduction in body weight and adipose tissue.<ref name="Bagheri Zolghadri Stanek 2022 p=3985">{{Cite journal |last=Bagheri |first=Soghra |last2=Zolghadri |first2=Samaneh |last3=Stanek |first3=Agata |date=2022-09-26 |title=Beneficial Effects of Anti-Inflammatory Diet in Modulating Gut Microbiota and Controlling Obesity |journal=Nutrients |publisher=MDPI AG |volume=14 |issue=19 |page=3985 |doi=10.3390/nu14193985 |issn=2072-6643 |pmc=9572805 |pmid=36235638 |doi-access=free}}</ref>

===Other===
[[C-reactive protein|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.<ref name="pmid19271113">{{Cite journal |vauthors=Kogiso T, Moriyoshi Y, Shimizu S, Nagahara H, Shiratori K |year=2009 |title=High-sensitivity C-reactive protein as a serum predictor of nonalcoholic fatty liver disease based on the Akaike Information Criterion scoring system in the general Japanese population |journal=Journal of Gastroenterology |volume=44 |issue=4 |pages=313–21 |doi=10.1007/s00535-009-0002-5 |pmid=19271113 |s2cid=1193178}}</ref> 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.<ref name="PMID20870782">{{Cite journal |vauthors=Brand JS, van der Tweel I, Grobbee DE, Emmelot-Vonk MH, van der Schouw YT |date=February 2011 |title=Testosterone, sex hormone-binding globulin and the metabolic syndrome: a systematic review and meta-analysis of observational studies |journal=International Journal of Epidemiology |volume=40 |issue=1 |pages=189–207 |doi=10.1093/ije/dyq158 |pmid=20870782 |doi-access=free}}</ref>

==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 |vauthors=Lakka TA, Laaksonen DE |date=February 2007 |title=Physical activity in prevention and treatment of the metabolic syndrome |journal=Applied Physiology, Nutrition, and Metabolism |volume=32 |issue=1 |pages=76–88 |doi=10.1139/h06-113 |pmid=17332786}}</ref> and a healthy, reduced calorie diet.<ref>{{Cite journal |vauthors=Feldeisen SE, Tucker KL |date=February 2007 |title=Nutritional strategies in the prevention and treatment of metabolic syndrome |journal=Applied Physiology, Nutrition, and Metabolism |volume=32 |issue=1 |pages=46–60 |doi=10.1139/h06-101 |pmid=17332784}}</ref>  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.<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 |vauthors=James PT, Rigby N, Leach R |date=February 2004 |title=The obesity epidemic, metabolic syndrome and future prevention strategies |journal=European Journal of Cardiovascular Prevention and Rehabilitation |volume=11 |issue=1 |pages=3–8 |doi=10.1097/01.hjr.0000114707.27531.48 |pmid=15167200 |s2cid=36797932}}</ref>

The [[Caerphilly Heart Disease Study]] followed 2,375 male subjects over 20 years and suggested the daily intake of an Imperial [[pint]] (~568 mL) of milk or equivalent dairy products more than halved the risk of metabolic syndrome.<ref>{{Cite journal |vauthors=Elwood PC, Pickering JE, Fehily AM |date=August 2007 |title=Milk and dairy consumption, diabetes and the metabolic syndrome: the Caerphilly prospective study |journal=Journal of Epidemiology and Community Health |volume=61 |issue=8 |pages=695–98 |doi=10.1136/jech.2006.053157 |pmc=2652996 |pmid=17630368}}</ref> Some subsequent studies support the authors' findings, while others dispute them.<ref>{{Cite journal |vauthors=Snijder MB, van der Heijden AA, van Dam RM, Stehouwer CD, Hiddink GJ, Nijpels G, Heine RJ, Bouter LM, Dekker JM |date=April 2007 |title=Is higher dairy consumption associated with lower body weight and fewer metabolic disturbances? The Hoorn Study |journal=The American Journal of Clinical Nutrition |volume=85 |issue=4 |pages=989–95 |doi=10.1093/ajcn/85.4.989 |pmid=17413097 |doi-access=free}}</ref> A systematic review of four [[randomized controlled trials]] said that, in the short term, a [[Paleolithic diet|Paleolithic nutritional]] pattern improved three of five measurable components of the metabolic syndrome in participants with at least one of the components.<ref>{{Cite journal |vauthors=Manheimer EW, van Zuuren EJ, Fedorowicz Z, Pijl H |date=October 2015 |title=Paleolithic nutrition for metabolic syndrome: systematic review and meta-analysis |journal=The American Journal of Clinical Nutrition |volume=102 |issue=4 |pages=922–32 |doi=10.3945/ajcn.115.113613 |pmc=4588744 |pmid=26269362}}</ref>

== Management ==
{{update section|date=December 2024}}

===Diet===
Dietary [[Low-carbohydrate diet|carbohydrate restriction]] reduces blood glucose levels, contributes to weight loss, and reduces the use of several medications that may be prescribed for metabolic syndrome.<ref>{{Cite journal |display-authors=6 |vauthors=Feinman RD, Pogozelski WK, Astrup A, Bernstein RK, Fine EJ, Westman EC, Accurso A, Frassetto L, Gower BA, McFarlane SI, Nielsen JV, Krarup T, Saslow L, Roth KS, Vernon MC, Volek JS, Wilshire GB, Dahlqvist A, Sundberg R, Childers A, Morrison K, Manninen AH, Dashti HM, Wood RJ, Wortman J, Worm N |date=January 2015 |title=Dietary carbohydrate restriction as the first approach in diabetes management: critical review and evidence base |journal=Nutrition |volume=31 |issue=1 |pages=1–13 |doi=10.1016/j.nut.2014.06.011 |pmid=25287761 |doi-access=free}}</ref> Studies suggest that meal timing and frequency can significantly impact the risk of developing metabolic syndrome. Research indicates that individuals who maintain regular meal timings and avoid eating late at night have a reduced risk of developing this condition.<ref>{{Cite journal |last=Alkhulaifi |first=F. |date=2022 |title=Meal Timing, Meal Frequency and Metabolic Syndrome |journal=Nutrients |volume=14 |issue=1719 |page=1719 |doi=10.3390/nu14091719 |pmc=9102985 |pmid=35565686 |doi-access=free}}</ref>

===Medications===
Generally, the individual disorders that compose the metabolic syndrome are treated separately.<ref name="ijms">{{Cite journal |vauthors=Srikanthan K, Feyh A, Visweshwar H, Shapiro JI, Sodhi K |year=2016 |title=Systematic Review of Metabolic Syndrome Biomarkers: A Panel for Early Detection, Management, and Risk Stratification in the West Virginian Population |journal=International Journal of Medical Sciences |volume=13 |issue=1 |pages=25–38 |doi=10.7150/ijms.13800 |pmc=4716817 |pmid=26816492}}</ref> [[Diuretic]]s and [[ACE inhibitor]]s may be used to treat hypertension. Various cholesterol medications may be useful if LDL cholesterol, triglycerides, and/or HDL cholesterol is abnormal.{{citation needed|date=June 2022}}

==Epidemiology==
{{Main|Epidemiology of metabolic syndrome}}
Approximately 20–25 percent of the world's adult population has the cluster of risk factors that is metabolic syndrome.<ref name="idf.org" />  In 2000, approximately 32% of U.S. adults had metabolic syndrome.<ref name="Ford ES">{{Cite journal |vauthors=Ford ES, Li C, Zhao G |date=September 2010 |title=Prevalence and correlates of metabolic syndrome based on a harmonious definition among adults in the US |url=https://zenodo.org/record/1230784 |journal=Journal of Diabetes |volume=2 |issue=3 |pages=180–93 |doi=10.1111/j.1753-0407.2010.00078.x |pmid=20923483 |s2cid=5145131 |doi-access=free}}</ref><ref name="Ford ES et al">{{Cite journal |vauthors=Ford ES, Giles WH, Mokdad AH |date=October 2004 |title=Increasing prevalence of the metabolic syndrome among u.s. Adults |journal=Diabetes Care |volume=27 |issue=10 |pages=2444–49 |doi=10.2337/diacare.27.10.2444 |pmid=15451914 |doi-access=free}}</ref> In more recent years that figure has climbed to 34%.<ref name="Ford ES et al" /><ref>{{Cite journal |vauthors=Mozumdar A, Liguori G |date=January 2011 |title=Persistent increase of prevalence of metabolic syndrome among U.S. adults: NHANES III to NHANES 1999–2006 |journal=Diabetes Care |volume=34 |issue=1 |pages=216–19 |doi=10.2337/dc10-0879 |pmc=3005489 |pmid=20889854}}</ref>

In young children, there is no consensus on how to measure metabolic syndrome since age-specific cut points and reference values that would indicate "high risk" have not been well established.<ref name="Metabolic syndrome in children">{{Cite journal |vauthors=Kamel M, Smith BT, Wahi G, Carsley S, Birken CS, Anderson LN |date=December 2018 |title=Continuous cardiometabolic risk score definitions in early childhood: a scoping review |journal=Obesity Reviews |volume=19 |issue=12 |pages=1688–99 |doi=10.1111/obr.12748 |pmid=30223304 |s2cid=52291692}}</ref> A continuous cardiometabolic risk summary score is often used for children instead of a dichotomous measure of metabolic syndrome.<ref name="Continuous measure for metabolic syndrome in children">{{Cite journal |vauthors=Chiarelli F, Mohn A |date=October 2017 |title=Early diagnosis of metabolic syndrome in children |journal=The Lancet. Child & Adolescent Health |volume=1 |issue=2 |pages=86–88 |doi=10.1016/S2352-4642(17)30043-3 |pmid=30169210}}</ref>

Other conditions<ref>{{Cite journal |last=Mendrick |first=Donna L |last2=Diehl |first2=Anna Mae |last3=Topor |first3=Lisa S |last4=Dietert |first4=Rodney R |last5=Will |first5=Yvonne |last6=La Merrill |first6=Michele A |last7=Bouret |first7=Sebastien |last8=Varma |first8=Vijayalaskshmi |last9=Hastings |first9=Kenneth L |last10=Schug |first10=Thaddeus T |last11=Emeigh Hart |first11=Susan G |last12=Burleson |first12=Florence G |date=2018-03-01 |title=Metabolic Syndrome and Associated Diseases: From the Bench to the Clinic |url=https://academic.oup.com/toxsci/article/162/1/36/4585010 |journal=Toxicological Sciences |language=en |volume=162 |issue=1 |pages=36–42 |doi=10.1093/toxsci/kfx233 |issn=1096-6080 |pmc=6256950 |pmid=29106690}}</ref> and specific microbiome diversity<ref>{{Cite journal |last=Fan |first=Yong |last2=Pedersen |first2=Oluf |date=January 2021 |title=Gut microbiota in human metabolic health and disease |url=https://www.nature.com/articles/s41579-020-0433-9 |journal=Nature Reviews Microbiology |language=en |volume=19 |issue=1 |pages=55–71 |doi=10.1038/s41579-020-0433-9 |issn=1740-1526 |pmid=32887946 |s2cid=256744684}}</ref> seems to be associated with metabolic syndrome, with certain-degree of gender-specificity.<ref>{{Cite journal |last=Pietropaoli |first=Davide |last2=Altamura |first2=Serena |last3=Ortu |first3=Eleonora |last4=Guerrini |first4=Luca |last5=Pizarro |first5=Theresa T. |last6=Ferri |first6=Claudio |last7=Del Pinto |first7=Rita |date=2023-04-10 |title=Association between metabolic syndrome components and gingival bleeding is women-specific: a nested cross-sectional study |journal=Journal of Translational Medicine |language=en |volume=21 |issue=1 |pages=252 |doi=10.1186/s12967-023-04072-z |issn=1479-5876 |pmc=10088168 |pmid=37038173 |doi-access=free}}</ref>

==History==
In 1921, Joslin first reported the association of diabetes with hypertension and hyperuricemia.<ref>{{Cite journal |vauthors=Joslin E |year=1921 |title=The Prevention of Diabetes Mellitus |journal=JAMA |volume=76 |issue=2 |pages=79–84 |doi=10.1001/jama.1921.02630020001001}}</ref>
In 1923, Kylin reported additional studies on the above triad.<ref>{{Cite journal |vauthors=Kylin E |date=1923 |title=[Studies of the hypertension-hyperglycemia-hyperuricemia syndrome] |journal=Zentralbl Inn Med |language=German |volume=44 |pages=105–27}}</ref>
In 1947, Vague observed that upper body obesity appeared to predispose to [[diabetes]], [[atherosclerosis]], [[gout]] and [[Calculus (medicine)|calculi]].<ref>{{Cite journal |vauthors=Vague J |date=1947 |title=La diffférenciacion sexuelle, facteur déterminant des formes de l'obésité. |journal=Presse Med |volume=30 |pages=339–40}}</ref>
In the late 1950s, the term metabolic syndrome was first used.

In 1967, Avogadro, Crepaldi and coworkers described six moderately obese people with diabetes, [[hypercholesterolemia]], and marked [[hypertriglyceridemia]], all of which improved when the affected people were put on a hypocaloric, low-carbohydrate diet.<ref>{{Cite journal |vauthors=Avogaro P, Crepaldi G, Enzi G, Tiengo A |year=1967 |title=Associazione di iperlipemia, diabete mellito e obesita' di medio grado |trans-title=Association of hyperlipemia, diabetes mellitus and middle-degree obesity |journal=Acta Diabetologica Latina |language=it |volume=4 |issue=4 |pages=572–90 |doi=10.1007/BF01544100 |s2cid=25839940}}</ref>
In 1977, Haller used the term ''metabolic syndrome'' for associations of obesity, diabetes mellitus, [[hyperlipoproteinemia]], [[hyperuricemia]], and [[hepatic steatosis]] when describing the additive effects of risk factors on atherosclerosis.<ref>{{Cite journal |vauthors=Haller H |date=April 1977 |title=[Epidermiology and associated risk factors of hyperlipoproteinemia] |journal=Zeitschrift für Sie Gesamte Innere Medizin und Ihre Grenzgebiete |volume=32 |issue=8 |pages=124–28 |pmid=883354}}</ref>
The same year, Singer used the term for associations of obesity, gout, diabetes mellitus, and hypertension with hyperlipoproteinemia.<ref>{{Cite journal |vauthors=Singer P |date=May 1977 |title=[Diagnosis of primary hyperlipoproteinemias] |journal=Zeitschrift für die Gesamte Innere Medizin und Ihre Grenzgebiete |volume=32 |issue=9 |pages=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]], [[hypercholesterolemia]], [[hypertriglyceridemia]], and hypertension) 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>{{Cite journal |vauthors=Phillips GB |date=July 1978 |title=Sex hormones, risk factors and cardiovascular disease |journal=The American Journal of Medicine |volume=65 |issue=1 |pages=7–11 |doi=10.1016/0002-9343(78)90685-X |pmid=356599}}</ref><ref>{{Cite journal |vauthors=Phillips GB |date=April 1977 |title=Relationship between serum sex hormones and glucose, insulin and lipid abnormalities in men with myocardial infarction |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=74 |issue=4 |pages=1729–33 |bibcode=1977PNAS...74.1729P |doi=10.1073/pnas.74.4.1729 |pmc=430867 |pmid=193114 |doi-access=free}}</ref>
In 1988, in his [[Banting Lectures|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>{{Cite journal |vauthors=Reaven GM |date=December 1988 |title=Banting lecture 1989. Role of insulin resistance in human disease |journal=Diabetes |volume=37 |issue=12 |pages=1595–607 |doi=10.2337/diabetes.37.12.1595 |pmid=3056758}}</ref>

== See also ==
* [[Metabolic disorder]]
* [[Portal-visceral hypothesis]]

== References ==
{{Reflist}}

{{Medical resources
|   ICD10          = E88.9
|   ICD9           = {{ICD9|277.7}}
|   ICDO           =
|   OMIM           = 605552
|   DiseasesDB     = 31955
|   MedlinePlus    = 007290
|   eMedicineSubj  =
|   eMedicineTopic =
|   MeshID         = D024821
}}

{{Authority control}}

{{DEFAULTSORT:Metabolic Syndrome}}
[[Category:Metabolic disorders]]
[[Category:Endocrine diseases]]
[[Category:Medical conditions related to obesity]]
[[Category:Syndromes affecting the endocrine system]]
[[Category:Syndromes with obesity]]