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The metabolic syndrome (insulin resistance syndrome or syndrome X)

Author
James B Meigs, MD, MPH
Section Editors
David M Nathan, MD
Joseph I Wolfsdorf, MB, BCh
Deputy Editor
Jean E Mulder, MD

INTRODUCTION

Obesity, particularly abdominal obesity, is associated with resistance to the effects of insulin on peripheral glucose and fatty acid utilization, often leading to type 2 diabetes mellitus. Insulin resistance, the associated hyperinsulinemia and hyperglycemia, and adipocyte cytokines (adipokines) may also lead to vascular endothelial dysfunction, an abnormal lipid profile, hypertension, and vascular inflammation, all of which promote the development of atherosclerotic cardiovascular disease (CVD) [1-4]. A similar profile can be seen in individuals with abdominal obesity who do not have an excess of total body weight [5-8].

The co-occurrence of metabolic risk factors for both type 2 diabetes and CVD (abdominal obesity, hyperglycemia, dyslipidemia, and hypertension) suggested the existence of a "metabolic syndrome" [1,9-11]. Other names applied to this constellation of findings have included syndrome X, the insulin resistance syndrome, the deadly quartet, or the obesity dyslipidemia syndrome [12]. Genetic predisposition, lack of exercise, and body fat distribution all affect the likelihood that a given obese subject will become overtly diabetic or develop CVD.

It should be noted that questions have been raised as to whether the metabolic syndrome, as currently defined, captures any unique pathophysiology implied by calling it a "syndrome," and whether metabolic syndrome confers risk beyond its individual components. These questions raise uncertainty about the value of diagnosing metabolic syndrome in individual patients [13,14]. These arguments will be reviewed at the end of this discussion (see 'A critical look at the metabolic syndrome' below). Regardless of whether the metabolic syndrome is considered a unique entity, the need is unquestioned to identify and manage its individual components to decrease morbidity and mortality associated with diabetes and CVD [15,16].

The definition, prevalence, clinical implications, and therapy of the metabolic syndrome will be reviewed here, including the limited data in children and adolescents. The pathogenesis of the relationship between obesity and type 2 diabetes and other causes of insulin resistance are discussed separately. (See "Pathogenesis of type 2 diabetes mellitus", section on 'Role of diet, obesity, and inflammation' and "Insulin resistance: Definition and clinical spectrum".)

The metabolic syndrome should not be confused with another disorder called syndrome X in which angina pectoris occurs in patients with normal coronary arteries. (See "Cardiac syndrome X: Angina pectoris with normal coronary arteries".)

                             

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References
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  1. Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 1988; 37:1595.
  2. DeFronzo RA, Ferrannini E. Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care 1991; 14:173.
  3. Lindsay RS, Howard BV. Cardiovascular risk associated with the metabolic syndrome. Curr Diab Rep 2004; 4:63.
  4. Koh KK, Han SH, Quon MJ. Inflammatory markers and the metabolic syndrome: insights from therapeutic interventions. J Am Coll Cardiol 2005; 46:1978.
  5. Richelsen B, Pedersen SB. Associations between different anthropometric measurements of fatness and metabolic risk parameters in non-obese, healthy, middle-aged men. Int J Obes Relat Metab Disord 1995; 19:169.
  6. Ruderman N, Chisholm D, Pi-Sunyer X, Schneider S. The metabolically obese, normal-weight individual revisited. Diabetes 1998; 47:699.
  7. Conus F, Allison DB, Rabasa-Lhoret R, et al. Metabolic and behavioral characteristics of metabolically obese but normal-weight women. J Clin Endocrinol Metab 2004; 89:5013.
  8. St-Onge MP, Janssen I, Heymsfield SB. Metabolic syndrome in normal-weight Americans: new definition of the metabolically obese, normal-weight individual. Diabetes Care 2004; 27:2222.
  9. Ferrannini E, Haffner SM, Mitchell BD, Stern MP. Hyperinsulinaemia: the key feature of a cardiovascular and metabolic syndrome. Diabetologia 1991; 34:416.
  10. Haffner SM, Valdez RA, Hazuda HP, et al. Prospective analysis of the insulin-resistance syndrome (syndrome X). Diabetes 1992; 41:715.
  11. Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet 2005; 365:1415.
  12. Grundy SM, Brewer HB Jr, Cleeman JI, et al. Definition of metabolic syndrome: Report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation 2004; 109:433.
  13. Kahn R, Buse J, Ferrannini E, et al. 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.
  14. Ferrannini E. Metabolic syndrome: a solution in search of a problem. J Clin Endocrinol Metab 2007; 92:396.
  15. Eckel RH, Kahn R, Robertson RM, Rizza RA. Preventing cardiovascular disease and diabetes: a call to action from the American Diabetes Association and the American Heart Association. Circulation 2006; 113:2943.
  16. Grundy SM. Metabolic syndrome: a multiplex cardiovascular risk factor. J Clin Endocrinol Metab 2007; 92:399.
  17. 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.
  18. 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.
  19. Matthews DR, Hosker JP, Rudenski AS, et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28:412.
  20. 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.
  21. Genuth S, Alberti KG, Bennett P, et al. Follow-up report on the diagnosis of diabetes mellitus. Diabetes Care 2003; 26:3160.
  22. 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.
  23. Alberti KG, Zimmet P, Shaw J, IDF Epidemiology Task Force Consensus Group. The metabolic syndrome--a new worldwide definition. Lancet 2005; 366:1059.
  24. 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.
  25. Meigs JB. Invited commentary: insulin resistance syndrome? Syndrome X? Multiple metabolic syndrome? A syndrome at all? Factor analysis reveals patterns in the fabric of correlated metabolic risk factors. Am J Epidemiol 2000; 152:908.
  26. International Diabetes Federation. The IDF consensus worldwide definition of the metabolic syndrome, 2006. http://www.idf.org/webdata/docs/MetS_def_update2006.pdf (Accessed on September 30, 2011).
  27. Ford ES. Prevalence of the metabolic syndrome defined by the International Diabetes Federation among adults in the U.S. Diabetes Care 2005; 28:2745.
  28. Adams RJ, Appleton S, Wilson DH, et al. Population comparison of two clinical approaches to the metabolic syndrome: implications of the new International Diabetes Federation consensus definition. Diabetes Care 2005; 28:2777.
  29. Lawlor DA, Smith GD, Ebrahim S. Does the new International Diabetes Federation definition of the metabolic syndrome predict CHD any more strongly than older definitions? Findings from the British Women's Heart and Health Study. Diabetologia 2006; 49:41.
  30. Meigs JB, Rutter MK, Sullivan LM, et al. Impact of insulin resistance on risk of type 2 diabetes and cardiovascular disease in people with metabolic syndrome. Diabetes Care 2007; 30:1219.
  31. 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.
  32. Cull CA, Jensen CC, Retnakaran R, Holman RR. Impact of the metabolic syndrome on macrovascular and microvascular outcomes in type 2 diabetes mellitus: United Kingdom Prospective Diabetes Study 78. Circulation 2007; 116:2119.
  33. Ridker PM, Buring JE, Cook NR, Rifai N. C-reactive protein, the metabolic syndrome, and risk of incident cardiovascular events: an 8-year follow-up of 14 719 initially healthy American women. Circulation 2003; 107:391.
  34. Festa A, D'Agostino R Jr, Howard G, et al. Chronic subclinical inflammation as part of the insulin resistance syndrome: the Insulin Resistance Atherosclerosis Study (IRAS). Circulation 2000; 102:42.
  35. Ridker PM. Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation 2003; 107:363.
  36. Festa A, D'Agostino R Jr, Tracy RP, et al. Elevated levels of acute-phase proteins and plasminogen activator inhibitor-1 predict the development of type 2 diabetes: the insulin resistance atherosclerosis study. Diabetes 2002; 51:1131.
  37. Pradhan AD, Manson JE, Rifai N, et al. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA 2001; 286:327.
  38. Hu FB, Meigs JB, Li TY, et al. Inflammatory markers and risk of developing type 2 diabetes in women. Diabetes 2004; 53:693.
  39. Rutter MK, Meigs JB, Sullivan LM, et al. C-reactive protein, the metabolic syndrome, and prediction of cardiovascular events in the Framingham Offspring Study. Circulation 2004; 110:380.
  40. Langenberg C, Bergstrom J, Scheidt-Nave C, et al. Cardiovascular death and the metabolic syndrome: role of adiposity-signaling hormones and inflammatory markers. Diabetes Care 2006; 29:1363.
  41. Timpson NJ, Lawlor DA, Harbord RM, et al. C-reactive protein and its role in metabolic syndrome: mendelian randomisation study. Lancet 2005; 366:1954.
  42. Pepys MB, Hirschfield GM. C-reactive protein: a critical update. J Clin Invest 2003; 111:1805.
  43. Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA 2002; 287:356.
  44. Ford ES, Giles WH, Mokdad AH. Increasing prevalence of the metabolic syndrome among u.s. Adults. Diabetes Care 2004; 27:2444.
  45. Wilson PW, D'Agostino RB, Parise H, et al. Metabolic syndrome as a precursor of cardiovascular disease and type 2 diabetes mellitus. Circulation 2005; 112:3066.
  46. Park YW, Zhu S, Palaniappan L, et al. The metabolic syndrome: prevalence and associated risk factor findings in the US population from the Third National Health and Nutrition Examination Survey, 1988-1994. Arch Intern Med 2003; 163:427.
  47. Wilson PW, Kannel WB, Silbershatz H, D'Agostino RB. Clustering of metabolic factors and coronary heart disease. Arch Intern Med 1999; 159:1104.
  48. Palaniappan L, Carnethon MR, Wang Y, et al. Predictors of the incident metabolic syndrome in adults: the Insulin Resistance Atherosclerosis Study. Diabetes Care 2004; 27:788.
  49. Mokdad AH, Serdula MK, Dietz WH, et al. The spread of the obesity epidemic in the United States, 1991-1998. JAMA 1999; 282:1519.
  50. Manson JE, Skerrett PJ, Greenland P, VanItallie TB. The escalating pandemics of obesity and sedentary lifestyle. A call to action for clinicians. Arch Intern Med 2004; 164:249.
  51. Ferreira I, Twisk JW, van Mechelen W, et al. Development of fatness, fitness, and lifestyle from adolescence to the age of 36 years: determinants of the metabolic syndrome in young adults: the amsterdam growth and health longitudinal study. Arch Intern Med 2005; 165:42.
  52. Meigs JB, Wilson PW, Fox CS, et al. Body mass index, metabolic syndrome, and risk of type 2 diabetes or cardiovascular disease. J Clin Endocrinol Metab 2006; 91:2906.
  53. Yaghootkar H, Scott RA, White CC, et al. Genetic evidence for a normal-weight "metabolically obese" phenotype linking insulin resistance, hypertension, coronary artery disease, and type 2 diabetes. Diabetes 2014; 63:4369.
  54. Gennuso KP, Gangnon RE, Thraen-Borowski KM, Colbert LH. Dose-response relationships between sedentary behaviour and the metabolic syndrome and its components. Diabetologia 2015; 58:485.
  55. Dhingra R, Sullivan L, Jacques PF, et al. Soft drink consumption and risk of developing cardiometabolic risk factors and the metabolic syndrome in middle-aged adults in the community. Circulation 2007; 116:480.
  56. Green AK, Jacques PF, Rogers G, et al. Sugar-sweetened beverages and prevalence of the metabolically abnormal phenotype in the Framingham Heart Study. Obesity (Silver Spring) 2014; 22:E157.
  57. Lamberti JS, Olson D, Crilly JF, et al. Prevalence of the metabolic syndrome among patients receiving clozapine. Am J Psychiatry 2006; 163:1273.
  58. LaMonte MJ, Barlow CE, Jurca R, et al. Cardiorespiratory fitness is inversely associated with the incidence of metabolic syndrome: a prospective study of men and women. Circulation 2005; 112:505.
  59. Pankow JS, Jacobs DR Jr, Steinberger J, et al. Insulin resistance and cardiovascular disease risk factors in children of parents with the insulin resistance (metabolic) syndrome. Diabetes Care 2004; 27:775.
  60. Mills GW, Avery PJ, McCarthy MI, et al. Heritability estimates for beta cell function and features of the insulin resistance syndrome in UK families with an increased susceptibility to type 2 diabetes. Diabetologia 2004; 47:732.
  61. Meigs JB, Panhuysen CI, Myers RH, et al. A genome-wide scan for loci linked to plasma levels of glucose and HbA(1c) in a community-based sample of Caucasian pedigrees: The Framingham Offspring Study. Diabetes 2002; 51:833.
  62. Panhuysen CI, Cupples LA, Wilson PW, et al. A genome scan for loci linked to quantitative insulin traits in persons without diabetes: the Framingham Offspring Study. Diabetologia 2003; 46:579.
  63. Grundy SM, Hansen B, Smith SC Jr, et al. Clinical management of metabolic syndrome: report of the American Heart Association/National Heart, Lung, and Blood Institute/American Diabetes Association conference on scientific issues related to management. Circulation 2004; 109:551.
  64. Rosenzweig JL, Ferrannini E, Grundy SM, et al. Primary prevention of cardiovascular disease and type 2 diabetes in patients at metabolic risk: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2008; 93:3671.
  65. Hanson RL, Imperatore G, Bennett PH, Knowler WC. Components of the "metabolic syndrome" and incidence of type 2 diabetes. Diabetes 2002; 51:3120.
  66. Resnick HE, Jones K, Ruotolo G, et al. Insulin resistance, the metabolic syndrome, and risk of incident cardiovascular disease in nondiabetic american indians: the Strong Heart Study. Diabetes Care 2003; 26:861.
  67. Klein BE, Klein R, Lee KE. Components of the metabolic syndrome and risk of cardiovascular disease and diabetes in Beaver Dam. Diabetes Care 2002; 25:1790.
  68. Sattar N, Gaw A, Scherbakova O, et al. Metabolic syndrome with and without C-reactive protein as a predictor of coronary heart disease and diabetes in the West of Scotland Coronary Prevention Study. Circulation 2003; 108:414.
  69. Sattar N, McConnachie A, Shaper AG, et al. Can metabolic syndrome usefully predict cardiovascular disease and diabetes? Outcome data from two prospective studies. Lancet 2008; 371:1927.
  70. Ford ES, Li C, Sattar N. Metabolic syndrome and incident diabetes: current state of the evidence. Diabetes Care 2008; 31:1898.
  71. Stern MP, Williams K, González-Villalpando C, et al. Does the metabolic syndrome improve identification of individuals at risk of type 2 diabetes and/or cardiovascular disease? Diabetes Care 2004; 27:2676.
  72. Cameron AJ, Magliano DJ, Zimmet PZ, et al. The metabolic syndrome as a tool for predicting future diabetes: the AusDiab study. J Intern Med 2008; 264:177.
  73. Ford ES. Risks for all-cause mortality, cardiovascular disease, and diabetes associated with the metabolic syndrome: a summary of the evidence. Diabetes Care 2005; 28:1769.
  74. Galassi A, Reynolds K, He J. Metabolic syndrome and risk of cardiovascular disease: a meta-analysis. Am J Med 2006; 119:812.
  75. Gami AS, Witt BJ, Howard DE, 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; 49:403.
  76. McLaughlin T, Abbasi F, Lamendola C, Reaven G. Heterogeneity in the prevalence of risk factors for cardiovascular disease and type 2 diabetes mellitus in obese individuals: effect of differences in insulin sensitivity. Arch Intern Med 2007; 167:642.
  77. Ingelsson E, Sullivan LM, Murabito JM, et al. Prevalence and prognostic impact of subclinical cardiovascular disease in individuals with the metabolic syndrome and diabetes. Diabetes 2007; 56:1718.
  78. Kohli P, Greenland P. Role of the metabolic syndrome in risk assessment for coronary heart disease. JAMA 2006; 295:819.
  79. Saely CH, Koch L, Schmid F, et al. Adult Treatment Panel III 2001 but not International Diabetes Federation 2005 criteria of the metabolic syndrome predict clinical cardiovascular events in subjects who underwent coronary angiography. Diabetes Care 2006; 29:901.
  80. Wannamethee SG, Shaper AG, Lennon L, Morris RW. Metabolic syndrome vs Framingham Risk Score for prediction of coronary heart disease, stroke, and type 2 diabetes mellitus. Arch Intern Med 2005; 165:2644.
  81. Marceau P, Biron S, Hould FS, et al. Liver pathology and the metabolic syndrome X in severe obesity. J Clin Endocrinol Metab 1999; 84:1513.
  82. Hamaguchi M, Kojima T, Takeda N, et al. The metabolic syndrome as a predictor of nonalcoholic fatty liver disease. Ann Intern Med 2005; 143:722.
  83. Hanley AJ, Williams K, Festa A, et al. Liver markers and development of the metabolic syndrome: the insulin resistance atherosclerosis study. Diabetes 2005; 54:3140.
  84. Chen J, Muntner P, Hamm LL, et al. The metabolic syndrome and chronic kidney disease in U.S. adults. Ann Intern Med 2004; 140:167.
  85. Zhang L, Zuo L, Wang F, et al. Metabolic syndrome and chronic kidney disease in a Chinese population aged 40 years and older. Mayo Clin Proc 2007; 82:822.
  86. Kurella M, Lo JC, Chertow GM. Metabolic syndrome and the risk for chronic kidney disease among nondiabetic adults. J Am Soc Nephrol 2005; 16:2134.
  87. Pasquali R, Gambineri A, Anconetani B, et al. The natural history of the metabolic syndrome in young women with the polycystic ovary syndrome and the effect of long-term oestrogen-progestagen treatment. Clin Endocrinol (Oxf) 1999; 50:517.
  88. Vgontzas AN, Papanicolaou DA, Bixler EO, et al. Sleep apnea and daytime sleepiness and fatigue: relation to visceral obesity, insulin resistance, and hypercytokinemia. J Clin Endocrinol Metab 2000; 85:1151.
  89. Ip MS, Lam B, Ng MM, et al. Obstructive sleep apnea is independently associated with insulin resistance. Am J Respir Crit Care Med 2002; 165:670.
  90. Choi HK, Ford ES. Prevalence of the metabolic syndrome in individuals with hyperuricemia. Am J Med 2007; 120:442.
  91. Choi HK, Ford ES, Li C, Curhan G. Prevalence of the metabolic syndrome in patients with gout: the Third National Health and Nutrition Examination Survey. Arthritis Rheum 2007; 57:109.
  92. Meigs JB. The metabolic syndrome. BMJ 2003; 327:61.
  93. Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002; 346:393.
  94. Magkos F, Yannakoulia M, Chan JL, Mantzoros CS. Management of the metabolic syndrome and type 2 diabetes through lifestyle modification. Annu Rev Nutr 2009; 29:223.
  95. Bassi N, Karagodin I, Wang S, et al. Lifestyle modification for metabolic syndrome: a systematic review. Am J Med 2014; 127:1242.e1.
  96. Lloyd-Jones DM, Liu K, Colangelo LA, et al. Consistently stable or decreased body mass index in young adulthood and longitudinal changes in metabolic syndrome components: the Coronary Artery Risk Development in Young Adults Study. Circulation 2007; 115:1004.
  97. Reaven G, Segal K, Hauptman J, et al. Effect of orlistat-assisted weight loss in decreasing coronary heart disease risk in patients with syndrome X. Am J Cardiol 2001; 87:827.
  98. Heymsfield SB, Segal KR, Hauptman J, et al. Effects of weight loss with orlistat on glucose tolerance and progression to type 2 diabetes in obese adults. Arch Intern Med 2000; 160:1321.
  99. Esposito K, Marfella R, Ciotola M, et al. Effect of a mediterranean-style diet on endothelial dysfunction and markers of vascular inflammation in the metabolic syndrome: a randomized trial. JAMA 2004; 292:1440.
  100. Tortosa A, Bes-Rastrollo M, Sanchez-Villegas A, et al. Mediterranean diet inversely associated with the incidence of metabolic syndrome: the SUN prospective cohort. Diabetes Care 2007; 30:2957.
  101. Salas-Salvadó J, Fernández-Ballart J, Ros E, et al. Effect of a Mediterranean diet supplemented with nuts on metabolic syndrome status: one-year results of the PREDIMED randomized trial. Arch Intern Med 2008; 168:2449.
  102. Kastorini CM, Milionis HJ, Esposito K, et al. The effect of Mediterranean diet on metabolic syndrome and its components: a meta-analysis of 50 studies and 534,906 individuals. J Am Coll Cardiol 2011; 57:1299.
  103. Azadbakht L, Mirmiran P, Esmaillzadeh A, et al. Beneficial effects of a Dietary Approaches to Stop Hypertension eating plan on features of the metabolic syndrome. Diabetes Care 2005; 28:2823.
  104. Brand-Miller J, Hayne S, Petocz P, Colagiuri S. Low-glycemic index diets in the management of diabetes: a meta-analysis of randomized controlled trials. Diabetes Care 2003; 26:2261.
  105. McKeown NM, Meigs JB, Liu S, et al. Carbohydrate nutrition, insulin resistance, and the prevalence of the metabolic syndrome in the Framingham Offspring Cohort. Diabetes Care 2004; 27:538.
  106. Ma Y, Olendzki BC, Wang J, et al. Single-component versus multicomponent dietary goals for the metabolic syndrome: a randomized trial. Ann Intern Med 2015; 162:248.
  107. Després JP, Pouliot MC, Moorjani S, et al. Loss of abdominal fat and metabolic response to exercise training in obese women. Am J Physiol 1991; 261:E159.
  108. Thompson PD, Buchner D, Pina IL, et al. Exercise and physical activity in the prevention and treatment of atherosclerotic cardiovascular disease: a statement from the Council on Clinical Cardiology (Subcommittee on Exercise, Rehabilitation, and Prevention) and the Council on Nutrition, Physical Activity, and Metabolism (Subcommittee on Physical Activity). Circulation 2003; 107:3109.
  109. Klein S, Fontana L, Young VL, et al. Absence of an effect of liposuction on insulin action and risk factors for coronary heart disease. N Engl J Med 2004; 350:2549.
  110. 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.
  111. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998; 352:854.
  112. Nathan DM, Buse JB, Davidson MB, et al. Management of hyperglycemia in type 2 diabetes: A consensus algorithm for the initiation and adjustment of therapy: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2006; 29:1963.
  113. Pearson TA, Blair SN, Daniels SR, et al. AHA Guidelines for Primary Prevention of Cardiovascular Disease and Stroke: 2002 Update: Consensus Panel Guide to Comprehensive Risk Reduction for Adult Patients Without Coronary or Other Atherosclerotic Vascular Diseases. American Heart Association Science Advisory and Coordinating Committee. Circulation 2002; 106:388.
  114. Eberly LE, Prineas R, Cohen JD, et al. Metabolic syndrome: risk factor distribution and 18-year mortality in the multiple risk factor intervention trial. Diabetes Care 2006; 29:123.
  115. Marroquin OC, Kip KE, Kelley DE, et al. Metabolic syndrome modifies the cardiovascular risk associated with angiographic coronary artery disease in women: a report from the Women's Ischemia Syndrome Evaluation. Circulation 2004; 109:714.
  116. Ballantyne CM, Olsson AG, Cook TJ, et al. Influence of low high-density lipoprotein cholesterol and elevated triglyceride on coronary heart disease events and response to simvastatin therapy in 4S. Circulation 2001; 104:3046.
  117. Pyörälä K, Ballantyne CM, Gumbiner B, et al. Reduction of cardiovascular events by simvastatin in nondiabetic coronary heart disease patients with and without the metabolic syndrome: subgroup analyses of the Scandinavian Simvastatin Survival Study (4S). Diabetes Care 2004; 27:1735.
  118. Deedwania P, Barter P, Carmena R, et al. Reduction of low-density lipoprotein cholesterol in patients with coronary heart disease and metabolic syndrome: analysis of the Treating to New Targets study. Lancet 2006; 368:919.
  119. Goodman E. Pediatric metabolic syndrome: smoke and mirrors or true magic? J Pediatr 2006; 148:149.
  120. Weiss R, Dziura J, Burgert TS, et al. Obesity and the metabolic syndrome in children and adolescents. N Engl J Med 2004; 350:2362.
  121. Cook S, Weitzman M, Auinger P, et al. Prevalence of a metabolic syndrome phenotype in adolescents: findings from the third National Health and Nutrition Examination Survey, 1988-1994. Arch Pediatr Adolesc Med 2003; 157:821.
  122. Jolliffe CJ, Janssen I. Development of age-specific adolescent metabolic syndrome criteria that are linked to the Adult Treatment Panel III and International Diabetes Federation criteria. J Am Coll Cardiol 2007; 49:891.
  123. Zimmet P, Alberti G, Kaufman F, et al. The metabolic syndrome in children and adolescents. Lancet 2007; 369:2059.
  124. Fernández JR, Redden DT, Pietrobelli A, Allison DB. Waist circumference percentiles in nationally representative samples of African-American, European-American, and Mexican-American children and adolescents. J Pediatr 2004; 145:439.
  125. Chi CH, Wang Y, Wilson DM, Robinson TN. Definition of metabolic syndrome in preadolescent girls. J Pediatr 2006; 148:788.
  126. Goodman E, Daniels SR, Meigs JB, Dolan LM. Instability in the diagnosis of metabolic syndrome in adolescents. Circulation 2007; 115:2316.
  127. DuBose KD, Stewart EE, Charbonneau SR, et al. Prevalence of the metabolic syndrome in elementary school children. Acta Paediatr 2006; 95:1005.
  128. Reinehr T, de Sousa G, Toschke AM, Andler W. Comparison of metabolic syndrome prevalence using eight different definitions: a critical approach. Arch Dis Child 2007; 92:1067.
  129. de Ferranti SD, Gauvreau K, Ludwig DS, et al. Prevalence of the metabolic syndrome in American adolescents: findings from the Third National Health and Nutrition Examination Survey. Circulation 2004; 110:2494.
  130. Stanley TL, Chen ML, Goodman E. The typology of metabolic syndrome in the transition to adulthood. J Clin Endocrinol Metab 2014; 99:1044.
  131. Retnakaran R, Zinman B, Connelly PW, et al. Nontraditional cardiovascular risk factors in pediatric metabolic syndrome. J Pediatr 2006; 148:176.
  132. Morrison JA, Friedman LA, Harlan WR, et al. Development of the metabolic syndrome in black and white adolescent girls: a longitudinal assessment. Pediatrics 2005; 116:1178.
  133. Gustafson JK, Yanoff LB, Easter BD, et al. The stability of metabolic syndrome in children and adolescents. J Clin Endocrinol Metab 2009; 94:4828.
  134. Morrison JA, Friedman LA, Gray-McGuire C. Metabolic syndrome in childhood predicts adult cardiovascular disease 25 years later: the Princeton Lipid Research Clinics Follow-up Study. Pediatrics 2007; 120:340.
  135. Sundström J, Vallhagen E, Risérus U, et al. Risk associated with the metabolic syndrome versus the sum of its individual components. Diabetes Care 2006; 29:1673.
  136. Bayturan O, Tuzcu EM, Lavoie A, et al. The metabolic syndrome, its component risk factors, and progression of coronary atherosclerosis. Arch Intern Med 2010; 170:478.
  137. López-Suárez A, Bascuñana-Quirell A, Beltrán-Robles M, et al. Metabolic syndrome does not improve the prediction of 5-year cardiovascular disease and total mortality over standard risk markers. Prospective population based study. Medicine (Baltimore) 2014; 93:e212.