Definition, History, and Management of the Metabolic Syndrome and Management Gaps

  • Josep VidalEmail author
  • Amanda Jiménez


The definition of the Metabolic Syndrome is still a work in progress despite a description of the association between visceral obesity and cardiovascular disease was already made by Morgagni back in the eighteenth century. In the absence of proper definition, the utility of the Metabolic Syndrome as tool to predict risk of future cardiovascular events or the occurrence of type 2 diabetes mellitus has inevitably been surrounded with confusion. Lifestyle modification aiming at weight loss and increased physical activity is the foundation of current management of the Metabolic Syndrome. All the components of the Metabolic Syndrome benefit from weight loss and increased physical activity. However, it is less clear to what extent the diagnosis of the Metabolic Syndrome should guide decisions involving the use of additional therapies either medical or surgical.


Metabolic syndrome Definition Therapy Cardiovascular disease Type 2 diabetes mellitus 


  1. 1.
    Enzi G, Busetto L, Inelmen EM, Coin A, Sergi G. Historical perspective: visceral obesity and related comorbidity in Joannes Baptista Morgagni’s ‘De sedibus et causis morborum per anatomen indagata’. Int J Obes Relat Metab Disord. 2003;27:534–5.PubMedCrossRefGoogle Scholar
  2. 2.
    Hitzenberger K. Uber den Blutdruck bei Diabetes Mellitus. Wiener Arch Innere Med. 1921;2:461–6.Google Scholar
  3. 3.
    Marañon G. Uber Hypertonie and Zuckerkrankheit. Zentralblatt für Innere Medizin. 1922;43:169–76.Google Scholar
  4. 4.
    Kylin E. Studien über das Hypertoni-Hyperglycemi-Hyperurikemi syndrom. Zentralblatt für Innere Medizin. 1923;44:105–12.Google Scholar
  5. 5.
    Vague J. La differentiation sexuelle. Facteur determinant des formes de l’obésite. Presse Med. 1947;55:339–41.PubMedGoogle Scholar
  6. 6.
    Vague J. The degree of masculine differentiation of obesities. A factor determining predisposition to diabetes, atherosclerosis, gout and uric calculous disease. Am J Clin Nutr. 1956;4:20–34.PubMedGoogle Scholar
  7. 7.
    Kissebah AH, Vydelingum N, Murray R, et al. Relation of body fat distribution to metabolic complications of obesity. J Clin Endocrinol Metab. 1982;54:254–60.PubMedCrossRefGoogle Scholar
  8. 8.
    Albrink MJ, Krauss RM, Lindgrem FT, von der Groeben J, Pan S, Wood PD. Intercorrelations among plasma high density lipoprotein, obesity and triglycerides in a normal population. Lipids. 1980;15:668–76.PubMedCrossRefGoogle Scholar
  9. 9.
    Larsson B, Bengtsson C, Björntorp P, et al. Is abdominal body fat distribution a major explanation for the sex difference in the incidence of myocardial infarction? The study of men born in 1913 and the study of women, Göteborg, Sweden. Am J Epidemiol. 1992;135:266–73.PubMedGoogle Scholar
  10. 10.
    Camus JP. Goutte, diabète, hyperlipémie: un trisyndrome métabolique. Rev Rhum. 1966;33:10–5.PubMedGoogle Scholar
  11. 11.
    Avogaro P, Crepaldi G. Plurimetabolic syndrome. Acta Diabetol Lat. 1967;4:572–80.CrossRefGoogle Scholar
  12. 12.
    Haller H. Epidermiology and associated risk factors of hyperlipoproteinemia. Z Gesamte Inn Med. 1977;32:124–8.PubMedGoogle Scholar
  13. 13.
    Hanefeld M, Leonhardt W. Das Metabolische Syndrom. Dt Gesundh Wesen. 1981;36:545–51.Google Scholar
  14. 14.
    Mehnert H, Kuhlmann H. Hypertonie und Diabetes Mellitus. Dtsch Med J. 1968;19:567–71.PubMedGoogle Scholar
  15. 15.
    Reaven GM. Banting Lecture 1988. Role of insulin resistance in human disease. Diabetes. 1988;37:1595–607.PubMedCrossRefGoogle Scholar
  16. 16.
    Bogardus C, Lillioja S, Mott DM, Hollenbeck C, Reaven G. Relationship between degree of obesity and in vivo insulin action in man. Am J Physiol. 1985;248:E286–91.PubMedGoogle Scholar
  17. 17.
    Reaven GM. Syndrome X: a short history. Ochsner J. 2001;3:124–5.PubMedPubMedCentralGoogle Scholar
  18. 18.
    Kahn SE, Prigeon RL, McCulloch DK, et al. Quantification of the relationship between insulin sensitivity and beta-cell function in human subjects. Evidence for a hyperbolic function. Diabetes. 1993;42:1663–72.PubMedCrossRefGoogle Scholar
  19. 19.
    Ferrannini E, Natali A, Bell P, et al. Insulin resistance and hypersecretion in obesity. J Clin Invest. 1997;100:1166–73.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Kaplan NM. The deadly quartet. Upper body obesity, glucose intolerance, hypertriglyceridemia and hypertension. Arch Intern Med. 1989;149:1514.PubMedCrossRefGoogle Scholar
  21. 21.
    DeFronzo RA, Ferrannini E. Insulin resistance: a multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia and atherosclerotic cardiovascular disease. Diabetes Care. 1991;14:173–94.PubMedCrossRefGoogle Scholar
  22. 22.
    Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med. 1998;15:539–53.PubMedCrossRefGoogle Scholar
  23. 23.
    Reaven GM. The metabolic syndrome: time to get off the merry-go-round? J Intern Med. 2011;269:127–36.PubMedCrossRefGoogle Scholar
  24. 24.
    Balkau B, Charles MA. Comment on the provisional report from the WHO consultation. European Group for the Study of Insulin Resistance (EGIR). Diabet Med. 1999;16:442–3.PubMedCrossRefGoogle Scholar
  25. 25.
    Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285:2486–97.CrossRefGoogle Scholar
  26. 26.
    Bloomgarden ZT. American Association of Clinical Endocrinologists (AACE) consensus conference on the insulin resistance syndrome: 25–26 August 2002, Washington, DC. Diabetes Care. 2003;26:1297–303.PubMedCrossRefGoogle Scholar
  27. 27.
    Alberti KG, Zimmet P, Shaw J, IDF Epidemiology Task Force Consensus Group. The metabolic syndrome--a new worldwide definition. Lancet. 2005;366:1059–62.PubMedCrossRefGoogle Scholar
  28. 28.
    Grundy SM, Cleeman JI, Daniels SR, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation. 2005;112:2735–52.PubMedCrossRefGoogle Scholar
  29. 29.
    Alberti KG, Eckel RH, Grundy SM, et al. 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. Circulation. 2009;120:1640–5.PubMedCrossRefGoogle Scholar
  30. 30.
    Simmons RK, Alberti KG, Gale EA, et al. The metabolic syndrome: useful concept or clinical tool? Report of a WHO Expert Consultation. Diabetologia. 2010;53:600–5.PubMedCrossRefGoogle Scholar
  31. 31.
    Povel CM, Beulens JW, van der Schouw YT, et al. Metabolic syndrome model definitions predicting type 2 diabetes and cardiovascular disease. Diabetes Care. 2013;36:362–8.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Kahn R, Buse J, Ferrannini E, Stern M. The metabolic syndrome: time for a critical appraisal. Joint statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2005;28:2289–304.PubMedCrossRefGoogle Scholar
  33. 33.
    Mottillo S, Filion KB, Genest J, et al. The metabolic syndrome and cardiovascular risk a systematic review and meta-analysis. J Am Coll Cardiol. 2010;56:1113–32.PubMedCrossRefGoogle Scholar
  34. 34.
    Stern MP, Williams K, González-Villalpando C, Hunt KJ, Haffner SM. Does the metabolic syndrome improve identification of individuals at risk of type 2 diabetes and/or cardiovascular disease? Diabetes Care. 2004;27:2676–81.PubMedCrossRefGoogle Scholar
  35. 35.
    McNeill AM, Rosamond WD, Girman CJ, et al. The metabolic syndrome and 11-year risk of incident cardiovascular disease in the atherosclerosis risk in communities study. Diabetes Care. 2005;28:385–90.PubMedCrossRefGoogle Scholar
  36. 36.
    Woodward M, Tunstall-Pedoe H. The metabolic syndrome is not a sensible tool for predicting the risk of coronary heart disease. Eur J Cardiovasc Prev Rehabil. 2009;16:210–4.PubMedCrossRefGoogle Scholar
  37. 37.
    Wannamethee SG. The metabolic syndrome and cardiovascular risk in the British Regional Heart Study. Int J Obes (Lond). 2008;32 Suppl 2:S25–9.CrossRefGoogle Scholar
  38. 38.
    Qiao Q, Laatikainen T, Zethelius B, et al. Comparison of definitions of metabolic syndrome in relation to the risk of developing stroke and coronary heart disease in Finnish and Swedish cohorts. Stroke. 2009;40:337–43.PubMedCrossRefGoogle Scholar
  39. 39.
    Ford ES, Li C, Sattar N. Metabolic syndrome and incident diabetes: current state of the evidence. Diabetes Care. 2008;31:1898–904.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Lorenzo C, Williams K, Hunt KJ, Haffner SM. The National Cholesterol Education Program - Adult Treatment Panel III, International Diabetes Federation, and World Health Organization definitions of the metabolic syndrome as predictors of incident cardiovascular disease and diabetes. Diabetes Care. 2007;30:8–13.PubMedCrossRefGoogle Scholar
  41. 41.
    Wilson PW, D’Agostino RB, Parise H, Sullivan L, Meigs JB. Metabolic syndrome as a precursor of cardiovascular disease and type 2 diabetes mellitus. Circulation. 2005;112:3066–72.PubMedCrossRefGoogle Scholar
  42. 42.
    Noble D, Mathur R, Dent T, Meads C, Greenhalgh T. Risk models and scores for type 2 diabetes: systematic review. BMJ. 2011;343:d7163.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Vidal J. Updated review on the benefits of weight loss. Int J Obes Relat Metab Disord. 2002;26 Suppl 4:S25–8.PubMedCrossRefGoogle Scholar
  44. 44.
    Norris SL, Zhang X, Avenell A, Gregg E, Schmid CH, Lau J. Long-term non-pharmacological weight loss interventions for adults with prediabetes. Cochrane Database Syst Rev. 2005; (2):CD005270Google Scholar
  45. 45.
    Hamman RF, Wing RR, Edelstein SL, et al. Effect of weight loss with lifestyle intervention on risk of diabetes. Diabetes Care. 2006;29:2102–7.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Diabetes Prevention Program Research Group, Knowler WC, Fowler SE, et al. 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. Lancet. 2009;374:1677–86.PubMedCentralCrossRefGoogle Scholar
  47. 47.
    Orchard TJ, Temprosa M, Goldberg R, et al. The effect of metformin and intensive lifestyle intervention on the metabolic syndrome: the Diabetes Prevention Program randomized trial. Ann Intern Med. 2005;142:611–9.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Siebenhofer A, Jeitler K, Berghold A, et al. Long-term effects of weight-reducing diets in hypertensive patients. Cochrane Database Syst Rev. 2011; (9):CD008274.Google Scholar
  49. 49.
    Dattilo AM, Kris-Etherton PM. Effects of weight reduction on blood lipids and lipoproteins: a meta-analysis. Am J Clin Nutr. 1992;56:320–8.PubMedGoogle Scholar
  50. 50.
    Gregory SM, Headley SA, Wood RJ. Effects of dietary macronutrient distribution on vascular integrity in obesity and metabolic syndrome. Nutr Rev. 2011;69:509–19.PubMedCrossRefGoogle Scholar
  51. 51.
    Vanhees L, Geladas N, Hansen D, et al. Importance of characteristics and modalities of physical activity and exercise in the management of cardiovascular health in individuals with cardiovascular risk factors: recommendations from the EACPR. Part II. Eur J Prev Cardiol. 2012;19:1005–33.PubMedCrossRefGoogle Scholar
  52. 52.
    Cornelissen VA, Fagard RH, Coeckelberghs E, Vanhees L. Impact of resistance training on blood pressure and other cardiovascular risk factors: a meta-analysis of randomized, controlled trials. Hypertension. 2011;58:950–8.PubMedCrossRefGoogle Scholar
  53. 53.
    Kelley GA, Kelley KS. Impact of progressive resistance training on lipids and lipoproteins in adults: a meta-analysis of randomized controlled trials. Prev Med. 2009;48:9–19.PubMedCrossRefGoogle Scholar
  54. 54.
    Wu T, Gao X, Chen M, van Dam RM. Long-term effectiveness of diet-plus-exercise interventions vs. diet-only interventions for weight loss: a meta-analysis. Obes Rev. 2009;10:313–23.PubMedCrossRefGoogle Scholar
  55. 55.
    Eilat-Adar S, Eldar M, Goldbourt U. Association of intentional changes in body weight with coronary heart disease event rates in overweight subjects who have an additional coronary risk factor. Am J Epidemiol. 2005;161:352–8.PubMedCrossRefGoogle Scholar
  56. 56.
    Simonsen MK, Hundrup YA, Obel EB, Grønbaek M, Heitmann BL. Intentional weight loss and mortality among initially healthy men and women. Nutr Rev. 2008;66:375–86.PubMedCrossRefGoogle Scholar
  57. 57.
    Torgerson JS, Hauptman J, Boldrin MN, Sjöström L. XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care. 2004;27:155–61.PubMedCrossRefGoogle Scholar
  58. 58.
    Look AHEAD Research Group, Wing RR. Long-term effects of a lifestyle intervention on weight and cardiovascular risk factors in individuals with type 2 diabetes mellitus: four-year results of the Look AHEAD trial. Arch Intern Med. 2010;170:1566–75.Google Scholar
  59. 59.
    Babio N, Bulló M, Salas-Salvadó J. Mediterranean diet and metabolic syndrome: the evidence. Public Health Nutr. 2009;12:1607–17.PubMedCrossRefGoogle Scholar
  60. 60.
    Buchwald H, Avidor Y, Braunwald E, Jensen MD, Pories W, Fahrbach K, Schoelles K. Bariatric surgery: a systematic review and meta-analysis. JAMA. 2004;292:1724–37.PubMedCrossRefGoogle Scholar
  61. 61.
    Sjöström L, Lindroos AK, Peltonen M, et al. Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N Engl J Med. 2004;351:2683–93.PubMedCrossRefGoogle Scholar
  62. 62.
    Carlsson LM, Peltonen M, Ahlin S, et al. Bariatric surgery and prevention of type 2 diabetes in Swedish obese subjects. N Engl J Med. 2012;367:695–704.PubMedCrossRefGoogle Scholar
  63. 63.
    Sjöholm K, Anveden A, Peltonen M, et al. Evaluation of current eligibility criteria for bariatric surgery: diabetes prevention and risk factor changes in the Swedish Obese Subjects (SOS) study. Diabetes Care. 2013;36:1335.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Sjöström L, Narbro K, Sjöström CD, et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med. 2007;357:741–52.PubMedCrossRefGoogle Scholar
  65. 65.
    Adams TD, Gress RE, Smith SC, et al. Long-term mortality after gastric bypass surgery. N Engl J Med. 2007;357:753–61.PubMedCrossRefGoogle Scholar
  66. 66.
    Sjöström L, Peltonen M, Jacobson P, et al. Bariatric surgery and long-term cardiovascular events. JAMA. 2012;307:56–65.PubMedCrossRefGoogle Scholar
  67. 67.
    Ford ES, Li C, Zhao G. Prevalence and correlates of metabolic syndrome based on a harmonious definition among adults in the US. J Diabetes. 2010;2:180–93.PubMedCrossRefGoogle Scholar
  68. 68.
    American Diabetes Association. Standards of medical care in diabetes--2013. Diabetes Care. 2013;36 Suppl 1:S11–66.PubMedCentralCrossRefGoogle Scholar
  69. 69.
    Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289:2560–72.PubMedCrossRefGoogle Scholar
  70. 70.
    DREAM (Diabetes REduction Assessment with ramipril and rosiglitazone Medication) Trial Investigators, Gerstein HC, Yusuf S, et al. Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet. 2006;368:1096–105.CrossRefGoogle Scholar
  71. 71.
    DREAM On (Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication Ongoing Follow-up) Investigators, Gerstein HC, Mohan V, et al. Long-term effect of rosiglitazone and/or ramipril on the incidence of diabetes. Diabetologia. 2011;54:487–95.CrossRefGoogle Scholar
  72. 72.
    Lamanna C, Monami M, Marchionni N, Mannucci E. Effect of metformin on cardiovascular events and mortality: a meta-analysis of randomized clinical trials. Diabetes Obes Metab. 2011;13:221–8.PubMedCrossRefGoogle Scholar
  73. 73.
    DREAM Trial Investigators, Dagenais GR, Gerstein HC, Holman R, et al. Effects of ramipril and rosiglitazone on cardiovascular and renal outcomes in people with impaired glucose tolerance or impaired fasting glucose: results of the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) trial. Diabetes Care. 2008;31:1007–14.CrossRefGoogle Scholar
  74. 74.
    Taylor F, Ward K, Moore TH, Burke M, Davey Smith G, Casas JP, Ebrahim S. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2011; (1):CD004816.Google Scholar
  75. 75.
    Lee M, Saver JL, Towfighi A, Chow J, Ovbiagele B. Efficacy of fibrates for cardiovascular risk reduction in persons with atherogenic dyslipidemia: a meta-analysis. Atherosclerosis. 2011;217:492–8.PubMedCrossRefGoogle Scholar
  76. 76.
    NAVIGATOR Study Group, McMurray JJ, Holman RR, et al. Effect of valsartan on the incidence of diabetes and cardiovascular events. N Engl J Med. 2010;362(16):1477–90.CrossRefGoogle Scholar

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© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Obesity Unit, Endocrinology and Diabetes DepartmentHospital Clínic UniversitariBarcelonaSpain

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