Metabolic syndrome is a constellation of abnormalities, such as insulin resistance, central obesity, dyslipidemia, and high blood pressure. The definition and criteria for diagnosing metabolic syndrome keep changing and are a topic of debate. Regardless of the true criteria, the collection of these metabolic abnormalities increases the risk of developing type II diabetes mellitus and cardiovascular disease. The pathogenesis of metabolic syndrome involves the deregulation of various metabolic pathways involved in fatty acid metabolism, mitochondrial function, and glucose utilization. Metabolic syndrome is associated with an increased risk of other disorders, like nonalcoholic fatty liver, polycystic ovarian disease current terminology (PCOS), Alzheimer\'s disease, lipodystrophy, and Cushing\'s syndrome. The management of metabolic syndrome begins with lifestyle modification followed by pharmacotherapy of the individual component of metabolic syndrome. Weight reduction and lifestyle modification remains the mainstay of therapy of metabolic syndrome. Since insulin resistance is the major pathology behind the disease, insulin sensitizers, such as metformin and thiazolidinedione, are of great use. Hypolipidemic and antihypertensive drugs are used for treating other components of this syndrome. With the development in the field of molecular biology, the therapeutic targets for treating the individual components of the syndrome have been refined. This review focuses on the etiopathogenesis of metabolic syndrome and highlights the current and future therapeutic targets.
Rochlani Y, Pothineni NV, Kovelamudi S, Mehta JL. Metabolic syndrome: pathophysiology, management, and modulation by natural compounds. Ther Adv Cardiovasc Dis 2017;11(8):215–225. DOI: 10.1177/1753944717711379.
Beltrán-Sánchez H, Harhay MO, Harhay MM, McElligott S. Prevalence and trends of metabolic syndrome in the adult US population, 1999–2010. J Am Coll Cardiol 2013;62(8):697–703. DOI: 10.1016/j.jacc.2013.05.064.
Ruderman NB, Shulman GL. Metabolic syndrome. In: Jameson JL, Groot JD, editors. Endocrinology: adult and pediatric. Elsevier; 2015. p. 752–764.
Monteiro R, Azevedo I. Chronic inflammation in obesity and the metabolic syndrome. Mediators Inflamm 2010;2010:289645. DOI: 10.1155/2010/289645.
Paschos P, Paletas K. Non alcoholic fatty liver disease and metabolic syndrome. Hippokratia 2009;13(1):9–19.
Hamaguchi M, Takeda N, Kojima T, Ohbora A, Kato T, Sarui H, et al. Identification of individuals with non-alcoholic fatty liver disease by the diagnostic criteria for the metabolic syndrome. World J Gastroenterol 2012;18(13):1508–1516. DOI: 10.3748/wjg.v18.i13.1508.
Mandrelle K, Kamath MS, Bondu DJ, Chandy A, Aleyamma T, George K. Prevalence of metabolic syndrome in women with polycystic ovary syndrome attending an infertility clinic in a tertiary care hospital in south India. J Hum Reprod Sci 2012;5(1):26–31. DOI: 10.4103/0974-1208.97791.
Braun S, Bitton-Worms K, LeRoith D. The link between the metabolic syndrome and cancer. Int J Biol Sci 2011;7(7):1003–1015. DOI: 10.7150/ijbs.7.1003.
Esposito K, Chiodini P, Colao A, Lenzi A, Giugliano D. Metabolic syndrome and risk of cancer: a systematic review and meta-analysis. Diabetes Care 2012;35(11):2402–2411. DOI: 10.2337/dc12-0336.
Callaghan BC, Xia R, Banerjee M, de Rekeneire N, Harris TB, Newman AB, et al. Metabolic syndrome components are associated with symptomatic polyneuropathy independent of glycemic status. Diabetes Care 2016;39(5):801–807. DOI: 10.2337/dc16-0081.
Frisardi V, Solfrizzi V, Seripa D, Capurso C, Santamato A, Sancarlo D, et al. Metabolic-cognitive syndrome: a cross-talk between metabolic syndrome and Alzheimer's disease. Ageing Res Rev 2010;9(4):399–417. DOI: 10.1016/j.arr.2010.04.007.
Coban S, Cander S, Altuner MS, Keles I, Gul OO. Does metabolic syndrome increase erectile dysfunction and lower urinary tract symptoms. Urol J 2014;11(4):1820–1824. DOI: https://doi.org/10.1089/met.2013.0150.
Chanson P, Salenave S. Metabolic syndrome in Cushing's syndrome. Neuroendocrinology 2010;1:96–101. DOI: 10.1159/000314272.
Iglesia R, Loria-Kohen V, Zulet M, Martinez J, Reglero G, Ramirez de Molina A. Dietary strategies implicated in the prevention and treatment of metabolic syndrome. Int J Mol Sci 2016;17(11):1877. DOI: 10.3390/ijms17111877.
Akbaraly TN, Tabak AG, Shipley MJ, Mura T, Singh-Manoux A, Ferrie JE, et al. Little change in diet after onset of type 2 diabetes, metabolic syndrome, and obesity in middle-aged adults: 11-year follow-up study. Diabetes Care 2016;39(3):e29–e30. DOI: 10.2337/dc15-2094.
Lee J, Kim Y, Jeon JY. Association between physical activity and the prevalence of metabolic syndrome: from the Korean National Health and Nutrition Examination Survey, 1999–2012. SpringerPlus 2016;5(1):1870. DOI: 10.1186/s40064-016-3514-5.
Henson J, Davies MJ, Bodicoat DH, Edwardson CL, Gill JMR, Stensel DJ, et al. Breaking up prolonged sitting with standing or walking attenuates the postprandial metabolic response in postmenopausal women: a randomized acute study. Diabetes Care 2016;39(1):130–138. DOI: 10.2337/dc15-1240.
Pérez-Martínez P, Mikhailidis DP, Athyros VG, Bullo M, Couture P, Covas MI, et al. Lifestyle recommendations for the prevention and management of metabolic syndrome: an international panel recommendation. Nutr Rev 2017;75(5):307–326. DOI: 10.1093/nutrit/nux014.
Wagh A, Stone NJ. Treatment of metabolic syndrome. Expert Rev Cardiovasc Ther 2004;2(2):213–228. DOI: 10.1586/14779072.2.2.213.
Sugimoto S, Nakajima H, Kosaka K, Hosoi H. Review: Miglitol has potential as a therapeutic drug against obesity. Nutr Metab (Lond) 2015;12:51. DOI: 10.1186/s12986-015-0048-8.
DeFronzo RA, Ratner RE, Han J, Kim DD, Fineman MS, Baron AD. Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes. Diabetes Care 2005;28(5):1092–1100. DOI: 10.2337/diacare.28.5.1092.
Chatterjee S, Ghosal S, Chatterjee S. Glucagon-like peptide-1 receptor agonists favorably address all components of metabolic syndrome. World J Diabetes 2016;7(18):441–445. DOI: 10.4239/wjd.v7.i18.441.
Rosen JB, Ballantyne CM, Hsueh WA, Lin J, Shah AK, Lowe RS, et al. Influence of metabolic syndrome factors and insulin resistance on the efficacy of ezetimibe/simvastatin and atorvastatin in patients with metabolic syndrome and atherosclerotic coronary heart disease risk. Lipids Health Dis 2015;14:103. DOI: 10.1186/s12944-015-0075-5. Available from: http://www.lipidworld.com/content/14/1/103.
Kargiotis K. Resolution of non-alcoholic steatohepatitis by rosuvastatin monotherapy in patients with metabolic syndrome. World J Gastroenterol 2015;21(25):7860. DOI: 10.3748/wjg.v21.i25.7860.
Gami AS, Witt BJ, Howard DE, Erwin PJ, Gami LA, Somers VK, et al. Metabolic syndrome and risk of incident cardiovascular events and death: a systematic review and meta-analysis of longitudinal studies. J Am Coll Cardiol 2007;49(4):403–414. DOI: 10.1016/j.jacc.2006.09.032.
Ginsberg HN, Elam MB, Lovato LC, Crouse JR, Leiter LA, Linz P, et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med 2010;362(17):1563–1574. DOI: 10.1056/NEJMoa1001282.
De Kloet AD, Krause EG, Woods SC. The renin angiotensin system and the metabolic syndrome. Physiol Behav 2010;100(5):525–534. DOI: 10.1016/j.physbeh.2010.03.018.
Kupreeva M, Diane A, Lehner R, Watts R, Ghosh M, Proctor S, et al. Effect of metformin and flutamide on insulin, lipogenic and androgen-estrogen signaling, and cardiometabolic risk in a PCOS-prone metabolic syndrome rodent model. Am J Physiol Endocrinol Metab 2019;316(1):E16–E33. DOI: 10.1152/ajpendo.00018.2018.
Ricci C, Gaeta M, Rausa E, Asti E, Bandera F, Bonavina L. Long-term effects of bariatric surgery on type II diabetes, hypertension and hyperlipidemia: a meta-analysis and meta-regression study with 5-year follow-up. Obes Surg 2015;25(3):397–405. DOI: 10.1007/s11695-014-1442-4.
Van Greevenbroek MMJ, Schalkwijk CG, Stehouwer CDA. Dysfunctional adipose tissue and low-grade inflammation in the management of the metabolic syndrome: current practices and future advances. F1000 Res 2016;5. DOI: 10.12688/f1000research.8971.1.