{{Infobox medical condition | 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 = [[Acanthosis nigricans]], [[erectile dysfunction]], [[hyperuricemia]], [[insulin resistance]], [[nonalcoholic fatty liver disease]], [[obesity]], [[polycystic ovarian syndrome]], [[prediabetes]] | 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 |article-number=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=https://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 simple surrogate index of upper-body subcutaneous fat. Values >{{cvt|40.25|cm}} (men) and >{{cvt|35.75|cm}} (women) are considered high risk for metabolic syndrome, and large neck circumference more than doubles risk.<ref>{{Cite journal |last1=Mohseni-Takalloo |first1=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 |article-number=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 |last1=Shyam |first1=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 increased risk of mechanical ventilation and mortality in hospitalized COVID-19 patients.<ref>{{Cite journal |last1=Di Bella |first1=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 |article-number=e3354 |doi=10.1002/dmrr.3354 |issn=1520-7552 |pmc=7300447 |pmid=32484298}}</ref><ref>{{Cite journal |last1=Di Bella |first1=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 [[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> It is also associated with a significantly increased risk of surgical complications across most types of surgery in a 2023 systematic review and meta-analysis of >13 million individuals.<ref>{{Cite journal |last1=Norris |first1=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 underlying metabolic syndrome are under investigation and only partially elucidated. Most affected people are older, obese, sedentary, and have some degree of insulin resistance. [[Stress (biology)|Stress]] can also contribute. Important [[risk factors]] include diet (particularly sugar-sweetened beverages),<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}}</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 behaviour<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 |article-number=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 and some medications,<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 |url-access=subscription }}</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 of excessive adipose expansion under sustained [[overeating]] and resulting [[lipotoxicity]] has also been proposed.<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>
Markers of systemic [[inflammation]] including [[C-reactive protein]], [[fibrinogen]], [[interleukin 6]], and [[tumor necrosis factor-alpha]] (TNF-α) are often increased. Some research has focused on increased [[uric acid]] levels from 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>
Modern "Western diet" patterns with high intake of energy-dense processed foods are a factor in the development of metabolic syndrome.<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 |page=560 |doi=10.1542/peds.2011-2912 |pmc=3289531 |pmid=22351884}}</ref> Rather than total adiposity, the core clinical component is visceral/ectopic fat, and 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> A chronic energy surplus unmatched by activity may lead to mitochondrial dysfunction and insulin resistance.<ref>{{Cite journal |last1=Bremer |first1=A. A. |last2=Mietus-Snyder |first2=M. |last3=Lustig |first3=R. H. |date=2012 |title=Toward a Unifying Hypothesis of Metabolic Syndrome |journal=Pediatrics |volume=129 |issue=3 |pages=557–570 |doi=10.1542/peds.2011-2912 |pmid=22351884 |pmc=3289531 }}</ref>
=== Stress === Prolonged [[chronic stress]] may contribute to metabolic syndrome via dysregulation of the [[hypothalamic–pituitary–adrenal 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> Elevated [[cortisol]] can raise [[glucose]] and [[insulin]] levels, promoting [[visceral adiposity]], insulin resistance, dyslipidaemia, and hypertension, and has effects on bone turnover.<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><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><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 |bibcode=2002Circu.106.2659B |s2cid=5992769 |doi-access=free}}</ref>
=== Pathophysiology === It is common for there to be a development of [[visceral fat]], after which [[adipocyte]]s increase [[blood plasma|plasma]] levels of [[TNF-α]] and alter levels of other adipokines (e.g., [[adiponectin]], [[resistin]], [[PAI-1]]). TNF-α can induce inflammatory [[cytokine]]s and may trigger 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> Rat models with high-sucrose diets have shown progression from hypertriglyceridaemia to visceral fat accumulation and insulin resistance. Increased adipose tissue elevates immune cells and chronic inflammation, contributing to hypertension, atherosclerosis and diabetes.<ref>Whitney, Ellie; Ralfes, R. Sharon. 2011. ''Understanding Nutrition''. [[Wadsworth Cengage Learning]]: Belmont, CA.</ref><ref>{{cite journal |last1=Paley |first1=Carole A. |last2=Johnson |first2=Mark I. |title=Abdominal obesity and metabolic syndrome: exercise as medicine? |journal=BMC Sports Sci Med Rehabil |date=2018 |volume=10 |article-number=7 |doi=10.1186/s13102-018-0097-1 |pmid=29755739 |pmc=5935926 |doi-access=free |issn=2052-1847}}</ref>
The [[endocannabinoid system]] may contribute to metabolic dysregulation.<ref name="ECS - metabolic disorders" /><ref name="ECS - MS" /><ref name="AA and endocannabinoids" /> Overproduction can alter reward circuitry and executive function, perpetuating unhealthy behaviours.{{medical citation needed|date=April 2016}} The brain modulates 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}}</ref><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=...}}</ref> Overfeeding with sucrose/fructose, particularly with high-fat intake, can induce features of metabolic syndrome in animals.<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> [[Arachidonic acid]]–derived mediators ([[eicosanoids]]; [[2-arachidonoylglycerol]]; [[anandamide]]) may link lipid oversupply and inflammation.<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>
== Diagnosis ==
=== NCEP === As of 2023, the U.S. [[National Cholesterol Education Program]] Adult Treatment Panel III (2001) remains widely used.<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 cm (40 in) men; ≥88 cm (35 in) women * Dyslipidaemia: TG ≥1.7 mmol/L (150 mg/dL) * Dyslipidaemia: HDL-C <40 mg/dL (men), <50 mg/dL (women) * Blood pressure ≥130/85 mmHg (or treated for hypertension) * Fasting plasma glucose ≥6.1 mmol/L (110 mg/dL)
=== 2009 Interim Joint Statement === The [[International Diabetes Federation]] Task Force and partner organisations harmonised criteria 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... |url=https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.109.192644 |journal=Circulation |volume=120 |issue=16 |pages=1640–45 |doi=10.1161/CIRCULATIONAHA.109.192644 |pmid=19805654}}</ref> Diagnosis is three or more of: * Elevated waist circumference (population- and country-specific) * Triglycerides ≥150 mg/dL (1.7 mmol/L) * Reduced HDL-C (≤40 mg/dL (1.0 mmol/L) men; ≤50 mg/dL (1.3 mmol/L) women) * Elevated blood pressure (systolic ≥130 and/or diastolic ≥85 mmHg) * Fasting glucose ≥100 mg/dL (5.55 mmol/L)<ref name="PMID19805654" />
This statement recognises population differences in waist risk thresholds and encourages common criteria with agreed cut points for international comparisons.<ref name="PMID19805654" />
The prior IDF and revised NCEP definitions are similar, but differ on assumptions when [[body mass index]] ≥30 kg/m<sup>2</sup> and on geography-specific waist cut points.{{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=https://web.archive.org/web/20140821000053/http://whqlibdoc.who.int/hq/1999/WHO_NCD_NCS_99.2.pdf |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 one of diabetes mellitus, impaired glucose tolerance, impaired fasting glucose or insulin resistance '''and''' two of: * Blood pressure ≥140/90 mmHg * [[Dyslipidemia]]: TG ≥1.695 mmol/L and HDL-C ≤0.9 mmol/L (men), ≤1.0 mmol/L (women) * Central obesity: waist:hip ratio >0.90 (men); >0.85 (women), or BMI >30 kg/m<sup>2</sup> * [[Microalbuminuria]]: urinary albumin excretion ≥20 μg/min or albumin:creatinine ≥30 mg/g
=== EGIR === The European Group for the Study of Insulin Resistance (1999) requires insulin resistance (top 25% fasting insulin among nondiabetic individuals) '''and''' two or more of:<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 ≥94 cm (37 in) men; ≥80 cm (31.5 in) women * Dyslipidaemia: TG ≥2.0 mmol/L (177 mg/dL) and/or HDL-C <1.0 mmol/L (38.61 mg/dL) or treated for dyslipidaemia * Blood pressure ≥140/90 mmHg or antihypertensive medication * Fasting plasma glucose ≥6.1 mmol/L (110 mg/dL)
=== Cardiometabolic index === The Cardiometabolic Index (CMI) estimates risk of type 2 diabetes, [[non-alcoholic fatty liver disease]], and metabolic issues from waist-to-height ratio and triglycerides-to-HDL-C ratio.<ref name="Pluta Dudzińska Lubkowska 2022 p=624">{{Cite journal |last1=Pluta |first1=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 has also been explored alongside cardiovascular disease and erectile dysfunction.<ref name="Chen Shi Huang Li 2019 p=108585">{{Cite journal |last1=Chen |first1=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 |article-number=108585 |doi=10.1016/j.biopha.2019.01.046 |issn=0753-3322 |pmid=30798136 |doi-access=free}}</ref> Anti-inflammatory dietary patterns may improve related markers.<ref name="Bagheri Zolghadri Stanek 2022 p=3985">{{Cite journal |last1=Bagheri |first1=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]] is used to predict cardiovascular risk in metabolic syndrome and may predict [[nonalcoholic fatty liver disease]].<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}}</ref> Reproductive disorders (such as polycystic ovary syndrome in women of reproductive age) and erectile dysfunction or decreased total testosterone in men have also been associated.<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 == Prevention of metabolic syndrome centres on improving modifiable lifestyle factors that contribute to excess visceral fat, insulin resistance, and cardiometabolic risk. Even modest, sustained changes in activity and diet have been shown to improve multiple components of the syndrome.<ref name=ADA2024/><ref name=Peterseim2024/>
Regular physical activity is strongly supported by clinical and public-health organizations. Guidelines from the American Heart Association recommend at least 150 minutes per week of moderate-intensity aerobic activity, or 75 minutes of vigorous activity, with additional muscle-strengthening exercises on two or more days per week.<ref name=AHA2024/> Walking—even in shorter bouts that accumulate to 30 minutes per day—is associated with measurable improvements in blood pressure, insulin sensitivity, and waist circumference.<ref name=Peterseim2024/>
Dietary patterns emphasizing whole foods appear beneficial. Evidence from observational studies and randomized trials supports Mediterranean-style eating, which is associated with reduced central adiposity and improved lipid and glycaemic measures.<ref name=Dominguez2023/> Calorie reduction, improved diet quality, and lowering intake of refined carbohydrates also contribute to improved metabolic parameters.<ref name=Feinman2015/> Time-restricted eating (a form of intermittent fasting) has shown preliminary benefits in reducing waist circumference and fasting glucose in adults with metabolic syndrome, though long-term effects remain under investigation.<ref name=Manoogian2024/>
Other behavioural factors influence prevention outcomes. Adequate sleep duration and quality have been linked to lower cardiometabolic risk, with insufficient sleep associated with higher rates of hypertension, obesity, and dysregulated glucose metabolism.<ref name=Eshera2023/> Reducing alcohol intake may also be protective, as heavy use can worsen hepatic and metabolic outcomes in people with underlying metabolic risk.<ref name=Hagstrom2024/>
Although individual-level changes are effective for many people, adherence varies widely in real-world settings.<ref name=Feinman2015/> Public-health bodies—including the International Obesity Taskforce—argue that sustained prevention requires population-level interventions, such as improved access to healthy foods, urban design that supports physical activity, and policies addressing socioeconomic drivers of obesity.<ref name="idf.org" />
== Management == Management focuses on reducing cardiovascular and metabolic risk through lifestyle modification, pharmacologic therapy, and, in selected cases, surgery.<ref name=Peterseim2024/> Because metabolic syndrome represents a cluster of interrelated conditions, treatment typically targets each component individually rather than the syndrome as a single entity.<ref name=Swarup2024/>
Lifestyle modification is the cornerstone of management of metabolic syndrome. A [[Randomized controlled trial|randomized control trial]] of 618 adults with metabolic syndrome evaluated an intensive lifestyle modification that included over six months to encourage increased vegetable intake, brisk walks, sensory awareness, and emotion regulation, compared with a control intervention of monthly educational mailings.<ref>{{Cite journal |last1=Powell |first1=Lynda H. |last2=Berkley-Patton |first2=Jannette |last3=Drees |first3=Betty M. |last4=Karavolos |first4=Kelly |last5=Lohse |first5=Barbara |last6=Masters |first6=Kevin S. |last7=Nicklas |first7=Jacinda M. |last8=Rothschild |first8=Steven K. |last9=Yeh |first9=Chen |last10=Zimmermann |first10=Laura J. |last11=Suzuki |first11=Sumihiro |last12=ELM Trial Research Group |date=2026-01-01 |title=Lifestyle Intervention for Sustained Remission of Metabolic Syndrome: A Randomized Clinical Trial |journal=JAMA Internal Medicine |volume=186 |issue=1 |pages=67–77 |doi=10.1001/jamainternmed.2025.5900 |issn=2168-6114 |pmc=12598583 |pmid=41207299}}</ref> Members of the intervention group were ~33% more likely to experience remission of metabolic syndrome.
=== Diet and meal timing === A Mediterranean-style eating pattern emphasizing vegetables, fruits, whole grains, legumes, nuts, and unsaturated fats—is associated with improvements in blood pressure, lipids, insulin sensitivity, and cardiovascular risk.<ref name=Dominguez2023/> Reduced-carbohydrate approaches may lower glucose and promote weight loss in insulin-resistant individuals.<ref name=Feinman2015/> Evidence on meal timing suggests time-restricted eating or avoidance of late-night meals can modestly improve glycaemic and lipid markers, though long-term data are limited.<ref name=Manoogian2024/> Guidance recommends tailoring dietary advice to personal preference, culture, and access to improve adherence.<ref name=Peterseim2024/>
=== Follow-up and equity considerations === Ongoing follow-up includes monitoring waist circumference, body weight, blood pressure, lipids, and fasting glucose or HbA1c.<ref name=Peterseim2024/> Recent guidance emphasises equitable care through culturally appropriate counselling, affordable medication access, and community-based support.<ref name=Giangregorio2024/>
=== Medications and therapies === Treatment of individual risk factors follows established cardiovascular and diabetes guidelines.<ref name=Swarup2024/> * '''Blood pressure:''' First-line agents include thiazide-type diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and calcium channel blockers. Selection depends on comorbid conditions and tolerance.<ref name=Swarup2024/> * '''Dyslipidaemia:''' Statins remain first-line therapy for lowering low-density lipoprotein cholesterol (LDL-C). Fibrates or omega-3 fatty acids may be added for persistent severe hypertriglyceridaemia.<ref name=Grundy2005/> * '''Glucose control:''' Lifestyle intervention is the foundation of therapy. When medications are required, glucose-lowering agents with demonstrated cardiovascular and renal benefits—such as glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT2) inhibitors—are preferred for individuals with type 2 diabetes or elevated cardiovascular risk.<ref name=ADA2024/> * '''Obesity management:''' Pharmacotherapies such as semaglutide and tirzepatide produce clinically significant weight loss and improvements in blood pressure, lipids, and glycaemic control. Randomized controlled trials have reported reduced major adverse cardiovascular events in adults with overweight or obesity and established cardiovascular disease.<ref name=Wilding2021/><ref name=Frias2022/><ref>{{Cite journal |last=Joseph |first=Jimmy |date=July 3, 2025 |title=The Impact of Semaglutide on Metabolic Syndrome: A Case Report |journal=Cureus |volume=17 |issue= 7|article-number=e87223 |doi=10.7759/cureus.87223 |pmid=40755669 |pmc=12317596 |doi-access=free }}</ref>
=== Physical activity and weight reduction === Weight loss of ~7–10% over 6–12 months improves BP, lipids, and insulin sensitivity.<ref name=Peterseim2024/> Public-health guidance advises ≥150 min/week moderate aerobic activity (or 75 min vigorous) plus muscle-strengthening ≥2 days/week.<ref name=AHA2024>{{cite web |title=AHA recommendations for physical activity in adults |url=https://www.heart.org/en/healthy-living/fitness/fitness-basics/aha-recs-for-physical-activity-in-adults |website=American Heart Association |date=10 March 2024 |access-date=12 November 2025}}</ref>
=== Sleep, tobacco, and alcohol === Inadequate/irregular sleep and untreated obstructive sleep apnoea increase metabolic and CV risk.<ref name=Eshera2023/> Smoking increases insulin resistance and CV risk; cessation reduces adverse outcomes.<ref name=Swarup2024/> High alcohol intake raises BP, TGs, and hepatic steatosis; moderation is advised.<ref name=Hagstrom2024/>
=== Surgery === Metabolic (bariatric) surgery is considered when lifestyle and pharmacotherapy are insufficient. Surgery is associated with durable weight loss and partial or complete remission of type 2 diabetes, hypertension, and dyslipidaemia.<ref name=Mirghani2023/> Guidelines endorse surgery for BMI ≥35 kg/m², or ≥30 kg/m² with metabolic complications.<ref name=Angrisani2023/>
== Epidemiology == {{Main|Epidemiology of metabolic syndrome}} Approximately 20–25% of the world's adults have metabolic syndrome.<ref name="idf.org" /> In 2000, ~32% of U.S. adults met criteria;<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> more recent estimates are ~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 measurement; age-specific cut points are not 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> Continuous risk scores are often used instead.<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> Microbiome composition and some conditions have been associated with metabolic syndrome, sometimes with gender-specific patterns.<ref>{{Cite journal |last1=Fan |first1=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 |url-access=subscription }}</ref><ref>{{Cite journal |last1=Pietropaoli |first1=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 |page=252 |doi=10.1186/s12967-023-04072-z |issn=1479-5876 |pmc=10088168 |pmid=37038173 |doi-access=free}}</ref>
== History == In 1921, Joslin reported the association of diabetes with hypertension and hyperuricaemia.<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 expanded on this 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 predisposed to [[diabetes]], [[atherosclerosis]], [[gout]] and [[Calculus (medicine)|calculi]].<ref>{{Cite journal |vauthors=Vague J |date=1947 |title=La différenciation sexuelle, facteur déterminant des formes de l'obésité. |journal=Presse Med |volume=30 |pages=339–40}}</ref> The term ''metabolic syndrome'' began appearing in the late 1950s. In 1967, Avogaro, Crepaldi and coworkers described moderately obese people with diabetes, [[hypercholesterolemia]], and marked [[hypertriglyceridemia]] that improved on hypocaloric, low-carbohydrate diets.<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, Hans Haller used the term for associations of obesity, diabetes mellitus, [[hyperlipoproteinemia]], [[hyperuricemia]], and [[hepatic steatosis]].<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 it for associations of obesity, gout, diabetes, 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 1977–1978, Gerald B. Phillips proposed a "constellation of abnormalities" ([[glucose intolerance]], [[hyperinsulinemia]], [[hypercholesterolemia]], [[hypertriglyceridemia]], hypertension) and hypothesised sex hormones as a linking factor.<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> The first comprehensive definition of the metabolic syndrome was given in 1981 by the German researchers Markolf Hanefeld and Wolfgang Leonhardt, Dresden, who defined it as a cluster of obesity, hyper- and dyslipoproteinemia, type 2 diabetes, gout, and hypertension, associated with an increased incidence of atherosclerotic vascular disease, fatty liver disease, and gallstones.<ref>{{Cite journal |last1=Hanefeld |first1=Markolf |last2=Leonhardt |first2=Wolfgang |date=1981 |title=Das metabolische Syndrom. |journal=Dt Gesundheitswesen. |volume=36 |pages=545–551}}</ref> In 1988, [[Gerald M. Reaven]]'s [[Banting Lectures|Banting lecture]] proposed insulin resistance as the underlying factor and coined ''syndrome X''.<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 == <references> <ref name=ADA2024>{{cite journal |author=American Diabetes Association |title=Standards of Care in Diabetes—2024 |journal=Diabetes Care |year=2024 |volume=47 |issue=Suppl 1 |pages=S50–S65 |doi=10.2337/dc24-S003 |pmid=38078581 |pmc=10725807}}</ref> <ref name=Angrisani2023>{{cite journal |last=Angrisani |first=L |title=Bariatric surgery worldwide 2023 update |journal=Obes Surg |year=2023 |volume=33 |issue=12 |pages=3962–3974 |doi=10.1136/bmjdrc-2023-003558 |pmid=37699720 |pmc=10503393 }}</ref> <ref name=Dominguez2023>{{cite journal |last=Dominguez |first=LJ |title=Mediterranean diet in the management and prevention of metabolic syndrome |journal=Nutrition Metab Cardiovasc Dis |year=2023 |volume=33 |issue=7 |pages=1588–1598 |doi=10.1016/j.numecd.2023.05.007 |pmid=37336718}}</ref> <ref name=Eshera2023>{{cite journal |last=Eshera |first=YM |title=Sleep is essential for cardiovascular health |journal=Curr Probl Cardiol |year=2023 |volume=48 |issue=4 |article-number=101042 |doi=10.1016/j.cpcardiol.2023.101042 |doi-broken-date=14 November 2025 }}</ref> <ref name=Feinman2015>{{cite journal |last=Feinman |first=RD |title=Dietary carbohydrate restriction as the first approach in diabetes management: critical review and evidence base |journal=Nutrition |year=2015 |volume=31 |issue=1 |pages=1–13 |doi=10.1016/j.nut.2014.06.011 |pmid=25287761}}</ref> <ref name=Frias2022>{{cite journal |last=Frias |first=JP |title=Tirzepatide once weekly for the treatment of obesity |journal=N Engl J Med |year=2022 |volume=387 |issue=3 |pages=205–216 |doi=10.1056/NEJMoa2206038 |pmid=35658024}}</ref> <ref name=Giangregorio2024>{{cite journal |last=Giangregorio |first=F |title=A systematic review of metabolic syndrome: key findings and practical insights |journal=J Clin Med |year=2024 |volume=13 |issue=8 |page=2800 |doi=10.3390/jcm13082800 |doi-broken-date=14 November 2025 |doi-access=free }}</ref> <ref name=Grundy2005>{{cite journal |last=Grundy |first=SM |title=Diagnosis and management of the metabolic syndrome |journal=Circulation |year=2005 |volume=112 |issue=17 |pages=2735–2752 |doi=10.1161/CIRCULATIONAHA.105.169404 |pmid=16157765}}</ref> <ref name=Hagstrom2024>{{cite journal |last=Hagström |first=H |title=Interactions between metabolic syndrome and alcohol consumption increase liver disease risk |journal=United European Gastroenterol J |year=2024 |volume=12 |issue=2 |pages=168–176 |doi=10.1002/ueg2.12524 |pmid=38381115 |pmc=10954435 }}</ref> <ref name="idf.org">{{cite web |title=Metabolic syndrome |url=https://idf.org/aboutdiabetes/risk-factors/metabolic-syndrome/ |website=International Diabetes Federation |access-date=12 November 2025}}</ref> <ref name=Manoogian2024>{{cite journal |last=Manoogian |first=ENC |title=Time-restricted eating in adults with metabolic syndrome |journal=Ann Intern Med |year=2024 |volume=177 |issue=4 |pages=556–565 |doi=10.7326/M24-0859 |pmid=39348690 |pmc=11929607 }}</ref> <ref name=Mirghani2023>{{cite journal |last=Mirghani |first=H |title=Metabolic surgery versus usual care: effects on diabetes and metabolic risk |journal=Diabetol Metab Syndr |year=2023 |volume=15 |issue=1 |page=1001 |doi=10.1186/s13098-023-01001-4 |doi-access=free |pmid=36829204 |pmc=9951503}}</ref> <ref name=Peterseim2024>{{cite journal |last=Peterseim |first=CM |title=Metabolic syndrome: an updated review on diagnosis and treatment |journal=J Prim Care Community Health |year=2024 |volume=15 |article-number=21501319241309168 |doi=10.1177/21501319241309168 |pmid=39714021 |pmc=11672556 }}</ref> <ref name=Swarup2024>{{cite book |last=Swarup |first=S |title=Metabolic Syndrome |year=2024 |publisher=StatPearls Publishing |location=Treasure Island, FL |chapter=Management}}</ref> <ref name=Wilding2021>{{cite journal |last=Wilding |first=JPH |title=Once-weekly semaglutide in adults with overweight or obesity |journal=N Engl J Med |year=2021 |volume=384 |issue=11 |pages=989–1002 |doi=10.1056/NEJMoa2032183 |pmid=33567185 |url=https://discovery.ucl.ac.uk/id/eprint/10127569/ }}</ref> </references>
[[Category:Metabolic disorders]]