the clustering of glucose intolerance , hypertension , dyslipidemia and obesity , particularly central obesity , has been termed metabolic syndrome1 . ever since metabolic syndrome was described by reaven4 in 1988 , various definitions have been published and revised , and numerous studies have explored its pathophysiology . when the concept of metabolic syndrome was first proposed , the primary pathological process was believed to be insulin resistance or hyperinsulinemia5 . in addition , many etiological factors have been linked to the development and progression of metabolic syndrome , including an altered inflammatory state9 , visceral adipose tissue abnormalities11 , and the activation of the sympathetic nervous system12 . although metabolic syndrome contains several unresolved matters , including ambiguous criteria , the inclusion of diabetes , a unifying mechanism and its role as a syndrome13 , its worldwide prevalence has increased rapidly into one of the biggest health problems . metabolic syndrome is known to increase cardiovascular morbidity and mortality , type  2 diabetes , and allcause mortality14 . the desired clinical response to metabolic syndrome is improved individual and national public health , and a mitigation of negative outcomes through comprehensive management . most studies agree that cardiovascular disease ( cvd ) is the major outcome of metabolic syndrome15 . however , whether type  2 diabetes mellitus is also a major outcome of metabolic syndrome or one of its components is a topic of debate . the present review describes various definitions and changes in the prevalence of the metabolic syndrome , and the significance of metabolic syndrome as a risk factor of type  2 diabetes mellitus and cvd . finally , we propose the clinical usefulness inherent to metabolic syndrome , especially as a predictor of incident diabetes . although most medical communities agree that obesity , hypertension , dyslipidemia and abnormal glucose tolerance should be factored into the diagnosis , no standard criteria have been set for metabolic syndrome . several clinical definitions have been proposed and used in clinical practice ( table  1 ) . aace , american association of clinical endocrinologists ; bmi , body mass index ; bp , blood pressure ; egir , european group for the study of insulin resistance ; fpg , fasting plasma glucose ; hdlc , highdensity lipoprotein cholesterol ; idf , international diabetes federation ; ifg , impaired fasting glucose ; igt , impaired glucose tolerance ; ncepatp  iii , national cholesterol education program adult treatment panel  iii ; tg , triglyceride ; uaer , urinary albumin excretion rate ; who , world health organization ; whr , waisttohip ratio . diagnosis of cardiovascular diseases ( cvd ) , hypertension , polycystic ovary syndrome , nonalcoholic fatty liver disease , or acanthosis nigricans ; family history of type  2 diabetes , hypertension or cvd ; history of gestational diabetes or glucose intolerance ; noncaucasian ethnicity ; sedentary lifestyle ; waist circumference ( wc ) > 40  inches in men and wc > 35  inches in women ; age > 40  years . europe , 94  cm in men and 80  cm in women ; south asian and chinese , 90  cm in men and 80  cm in women ; japanese , 85  cm in men and 90  cm in women ; south and central america , south asian recommendations until more specific data become available ; subsaharan africa , eastern mediterranean and middle east populations , european data until more specific data becomes available . the first formalized definition of metabolic syndrome was introduced in 1998 by a group who was consulted by the world health organization ( who ) for a definition of diabetes1 . the diagnostic criteria included markers of abnormal glucose metabolism or insulin resistance , plus at least two out of four risk factors , which included obesity , hypertension , elevated triglycerides and/or reduced highdensity lipoprotein ( hdl ) cholesterol , and microalbuminuria . insulin resistance , as measured by the homeostasis model assessment of insulin resistance ( homair ) or the euglycemic hyperinsulinemic clamp technique , is a key factor of the who diagnostic criteria that does not exclude type  2 diabetes mellitus . the diagnostic criteria posed by the european group for the study of insulin resistance ( egir ) in 19992 and by american association of clinical endocrinologists ( aace ) in 200318 also emphasized the presence of insulin resistance . in the three aforementioned definitions listed , both impaired fasting glucose ( ifg ) and impaired glucose tolerance ( igt ) were noted as markers of abnormal glucose metabolism . however , in contrast to the who definition , patients with type  2 diabetes were not included in the egir and aace criteria . the most commonly used criteria emerged from the national cholesterol education program adult treatment panel  iii ( ncepatp  iii ) in 20013 . the presence of three of the five risk factors warrants a metabolic syndrome diagnosis . under the direction of the american diabetes association ( ada ) , the definition of dysglycemic factor was changed from a fasting plasma glucose ( fpg ) higher than 110  mg / dl in 2001 to a fpg higher than 100  mg / dl in 200619 . the international diabetes federation ( idf ) , american heart association ( aha ) , and national heart , lung , and blood institute ( nhlbi ) define metabolic syndrome as central obesity based on waist circumference plus two or more additional metabolic risk factors20 . central obesity criteria were revised in 2005 and 2009 ; they applied different classification criteria based on ethnicity and risk factor status of cvd . type  2 diabetes is included ; however , the igt criteria are not in ncep or idf . in contrast , these approaches are limited , because they underestimate the prevalence of igt and insulin resistance14 . ageadjusted prevalence increased from 29.2% in the national health and nutrition examination survey ( nhanes )  iii to 34.2% in nhanes 1999200622 . ageadjusted prevalence in the south korea nhanes ( knhanes ) 1998 was 24.9% , and increased to 31.3% in the knhanes 2007 with the application of revised ncep criteria23 . distinct and rapid increases in prevalence occur in women aged at least 50  years , after menopause , whereas metabolic syndrome in men aged at least 60  years decreases gradually ; and the prevalence in adolescents increased from 6.8% in knhanes 1998 to 9.2% in knhanes 200124 , to 13.0% in knhanes 200525 . in china , variance in the prevalence is a result of the use of differing criteria and inclusion of different ethnicities . in a metaanalysis in 2007 , nestel et  al.27 reported prevalence ranges of 1030% in several asian countries , including south korea , china , singapore , taiwan , hong kong and the philippines . for japan , the diagnostic criteria for central obesity differ from other asian countries , with waist circumference measurements of more than 85  cm for males and 90  cm for females . based on this definition , prevalence was 22.8% for men and 8.7% for women in the japanese national health and nutrition survey ( nhns ) 200328 . however , when other criteria were applied ( waist circumference 85  cm for males and   80  cm for females ) , the prevalence in females was increased from 8.7 to 19.2% . the prevalence of metabolic syndrome was 22.0% based on idf , 16.9% based on ncep and 23.3% based on modified ncep criteria from the nantong metabolic syndrome study ( nmss ) that was carried out in china in 2007200826 . numerous studies have confirmed the prognostic significance of metabolic syndrome on cardiovascular outcomes , including some negative results ( table  2 ) . ci , confidence interval ; bmi , body mass index ; egir , european group for the study of insulin resistance ; f / u , followup period ; idf , international diabetes federation ; ir , insulin resistance ; ncep , national cholesterol education program ; nhanes , national health and nutrition examination survey ; rr , relative risks ; who , world health organization . the results of the botnia study on 4,483 middleaged participants in finland and sweden showed a marked increase in cardiovascular mortality in participants with metabolic syndrome during a 6.9year followup period ( 12.0 vs 2.2% , p  <  0.001)15 . in the kuopio ischemic heart disease risk factor study , metabolic syndrome was associated with a 2.5 to 2.8fold greater risk of death from any cardiovascular cause29 . however , the relative risks ( rr ) and statistical significance varied with differing definitions of metabolic syndrome . the rr associated with who definitions was significant in all adjustment models ; however , when the ncep criteria ( waist circumference over 94  cm ) were used , no statistical significance was found in the association between rr and cvd mortality after adjustment for conventional risk factors , such as age , examination year , lowdensity lipoprotein ( ldl ) cholesterol , smoking status and family history of coronary heart disease . a metaanalysis on the 87 studies that used ncep or revised ncep definitions confirmed that metabolic syndrome is associated with a twofold increase in cardiovascular outcomes17 . the rr was 2.35 ( 95% confidence interval [ ci ] 2.022.73 ) for all cvd , 2.40 ( 95% ci 1.873.08 ) for cvd mortality , 1.99 ( 95% ci 1.612.46 ) for myocardial infarction and 2.27 ( 95% ci 1.802.85 ) for stroke . the hisayama study , 14year prospective study that included 2,452 middleaged japanese individuals , confirmed that the hazard ratio ( hr ) of cvd events was 1.86 ( 95% ci 1.322.62 ) in men with metabolic syndrome and 1.70 ( 95% ci 1.222.36 ) in women , after multivariable adjustment30 . wilson et  al.32 determined that the rr of coronary heart diseases was significantly higher in women than in men , although they did share the same number of metabolic risk factors . in that study , the presence of three or more metabolic risk factors increased the risk for coronary heart diseases ( chd ) 2.5fold in men and approximately sixfold in women during the 16year followup period of middleaged adults . in the presence of two risk factors , a study of 2,435 korean participants ( age range 2078  years ) showed that the odds ratios ( or ) for cvd were higher in women ( or 4.04 ; 95% ci 1.789.14 ) than in men ( or 1.98 ; 95% ci 1.303.03)31 . in the beaver dam study , the incidence of cvd was 2.5% in a group to have 0 components of the metabolic syndrome by who definition and 14.9% in four more risk factors16 . the or was 1.95 ( 95% ci 0.914.16 ) in the group with one risk factor , 2.05 ( 95% ci 0.964.40 ) in the group with two risk factors , 2.70 ( 95% ci 1.225.98 ) in the group with three risk factors and 5.86 ( 95% ci 2.5113.66 ) in the group with four or more risk factors . in the framingham heart study offspring study , the ageadjusted rr for cvd gradually increased as the number of risk factors increased in both men and women33 . in men , the rr was 1.48 ( 95% ci 0.693.16 ) for one or two components and 3.99 ( 95% ci 1.898.41 ) for three or more components . in women , the rr was 3.39 ( 95% ci 1.318.81 ) for one or two components and 5.95 ( 95% ci 2.2016.11 ) for three or more components . many largescale clinical trials and metaanalyses reported that the presence of metabolic syndrome , regardless of definition , was highly predictive of newonset type  2 diabetes in many different populations ( table  3 ) . some studies showed that the rr for incident diabetes is higher than it is for cvd34 . based on a metaanalysis of 42,419 participants from 16 cohorts , the average estimated rr for incident diabetes was 3.55.2 , and did not differ appreciably with each definition . the insulin resistance atherosclerosis study ( iras ) showed that the or for diabetes development based on the ncep and idf definitions was similar to the who definition , despite the use of modified risk factors35 . the study of aboriginal canadians showed a prevalence of diabetes three to fivefold higher than in nonaboriginal canadians , and metabolic syndrome had associated with incident diabetes regardless of the use of the ncep criteria ( or 2.03 ; 95% ci 1.13.75 ) or idf criteria ( or 2.14 ; 95% ci 1.293.55 ) to define metabolic syndrome36 . in contrast , cameron et  al.37 reported a higher or for the who criteria ( or 4.6 ; 95% ci 3.56.0 ) compared with egir criteria ( or 3.2 ; 95% ci 2.34.3 ) , ncep criteria ( or 3.1 ; 95% ci 2.34.0 ) and idf criteria ( or 3.0 ; 95% ci 2.24.2 ) . in addition , the or for incident diabetes in a study of 4,756 iranian subjects was highest using the who criteria ( or 11.0 ; 95% ci 7.915.3 ) during the 3.6year followup period38 . in that study , the or using the idf criteria was 4.3 ( 95% ci 3.06.0 ) , the original ncep criteria ( fpg    110  mg / dl ) was 3.7 ( 95% ci 2.75.1 ) , and using modified ncep criteria ( fpg    100  mg / dl ) was 4.9 ( 95% ci 3.56.9 ) . according to a metaanalysis carried out by ford et  al.34 , the randomeffects summary rr was 5.17 ( 95% ci 3.996.69 ) for the who 1999 definition , 4.45 ( 95% ci 2.418.22 ) for the egir 1999 definition , 3.53 ( 95% ci 2.844.39 ) for the ncep 2001 definition and 4.42 ( 95% ci 3.305.92 ) for the idf 2005 definition . ci , confidence interval ; egir , european group for the study of insulin resistance ; f / u , followup period ; fpg , fasting plasma glucose ; hr , hazard ratio ; idf , international diabetes federation ; ifg , impaired fasting glucose ; igt , impaired glucose tolerance ; ncep , national cholesterol education program ; nhanes , national health and nutrition examination survey ; rr , relative risks ; who , world health organization . to test which criteria enable improved predictability for the development of diabetes , we reviewed several statistical analyses that varied according to sensitivity , specificity , positive predictive values ( ppvs ) , negative predictive values ( npvs ) and the area under the receiver operating characteristics curve ( aroc ) . the sensitivity ranged from 0.224 to 0.722 , and the specificity ranged from 0.613 to 0.93937 . a factor analysis study of 1,918 pima indians confirmed that the who definition led to superior sensitivity and specificity compared with the ncep definition , because the former weights the presence of insulin resistance43 . also , in a longitudinal survey of 3,198 mauritius subjects , the who definitions resulted in a higher value of sensitivity ( 42.1% ) and ppv ( 26.8% ) compared with the idf and ncep definitions37 . however , differences among the arocs ( range 0.680.86 ) were small and insignificant , despite the differing criteria14 . the predictability of metabolic syndrome for incident diabetes was superior to the predictability associated with either the framingham risk score ( frs)47 or classical clinical risk factors excluding laboratory parameters , such as fpg , triglyceride , hdlcholesterol and blood pressure33 . several studies examined that the number of metabolic syndrome components associated with the risk of type  2 diabetes16 . according to a substudy on 3,323 members of the framingham heart study offspring study , the rr for type  2 diabetes had increased with the number of metabolic syndrome components when the necp criteria were applied33 . the adjusted rr for participants with three abnormalities or four more abnormalities was 4.56 ( 95% ci 2.488.78 ) and 10.88 ( 95% ci 5.7720.50 ) , respectively , in the british regional heart study47 . in the west of scotland coronary prevention study , sattar et  al.48 used the ncep definition based on body mass index ( bmi ) instead of waist circumference , with or without the inclusion of creactive protein ( crp ) . the estimated rr for participants with three abnormalities or four more abnormalities was 7.26 ( 95% ci 2.2523.40 ) and 24.4 ( 95% ci 7.5379.6 ) . in the beaver dam study , klein et  al.16 used a modified who definition to determine that the or for the incidence of diabetes was 9.37 ( 95% ci 2.2239.59 ) in the group with three abnormalities and 33.67 ( 95% ci 7.93142.96 ) in the group with four or more abnormalities . another study that was not based on one of the major definitions also reported that the rr relates to three or more risk factors49 . among the components of metabolic syndrome , ifg has been shown as the strongest predictor for type  2 diabetes development37 . subjects with metabolic syndrome , which included the ifg trait , showed a rr of 11.0 ( 95% ci 8.114.9 ) , whereas the rr for subjects excluding ifg were 5.0 ( 95% ci 3.76.8 ) in the framingham offspring study33 . lorenzo et  al.41 showed that the or of incidental diabetes was 5.03 ( 95% ci 3.397.48 ) in participants with metabolic syndrome excluding ifg , 7.07 ( 95% ci 3.3215.1 ) in participants without metabolic syndrome including ifg , and 21.0 ( 95% ci 13.133.8 ) in participants with metabolic syndrome including ifg when the ncep criteria were used . the trend is also similar to the idf definition ( 4.51 [ 95% ci 3.056.68 ] vs 10.5 [ 95% ci 5.5024.3 ] vs 21.5 [ 95% ci 13.334.8 ] ) . in a recently published study on older populations in finland , the hr of each metabolic syndrome component for the development of type  2 diabetes was 1.75 ( 95% ci 1.042.95 ) for the obesity factor , 1.34 ( 95% ci 0.782.31 ) for the triglyceride factor , 1.60 ( 95% ci 0.912.81 ) for the hdlcholesterol factor , 1.87 ( 95% ci 0.457.76 ) for the blood pressure factor and 5.16 ( 95% ci 2.689.93 ) for the ifg factor51 . the strong relationship between metabolic syndrome with ifg and incident type  2 diabetes mellitus was not predictive of cvd . whether other components ( except for fpg ) hwang et  al.31 reported that a dramatic decrease in the risk of incident diabetes was observed in men after the initial fpg was adjusted , and metabolic syndrome without ifg was not associated with incident diabetes in women . however , the individual components of metabolic syndrome associated independently with risk for incident diabetes . as aforementioned , metabolic syndrome without ifg associated significantly with risk for incident diabetes ; however , the rr in this case was less than the rr in metabolic syndrome with ifg . a few studies have shown that the incorporation of some markers not of traditional metabolic syndrome components can be used as new metabolic syndrome components . in the european investigation into cancer and nutrition ( epic)nl , monitoring project on risk factors for chronic diseases ( morgen ) study , the predictive ability of type  2 diabetes in the extended model with high sensitivity of crp ( hscrp ) was slightly better than the predictive ability of the standard model of metabolic syndrome52 . furthermore , several studies have considered additional features , such as markers of liver function , uric acid and albumin20 . however some concern has emerged with regard to the lack of certainty inherent to metabolic syndrome , its pathogenesis and its value as a risk marker of cvd13 . nevertheless , the syndrome is used widely and conveniently in clinical practice and research fields ; an important aspect of its clinical significance is the visualization of the risk for cvd and type  2 diabetes development . by receiving a diagnosis of metabolic syndrome , patients might become motivated to actively carry out lifestyle modifications , and physicians can implement the focused risk management and comprehensive implementation approaches available to them to mitigate major complications . the debate has continued on the inclusion of type  2 diabetes mellitus in definitions of metabolic syndrome ( figure  1)55 . early detection of individuals at high risk for type  2 diabetes is essential not only for the prevention of diabetes itself , but also to decrease associated cardiovascular complications . as aforementioned , metabolic syndrome is ideal as a predictor of incident diabetes . with the inclusion of diabetes in the defining criteria , in addition , physicians should not expect effects from concurrent prevention measures for incident type  2 diabetes and its complications to overlap with active intervention of metabolic syndrome . therefore , heavy consideration should be given to the exclusion of diabetes from the definition , and more focus should fall on the role of metabolic syndrome as an intervention tool for diabetes prevention . ( a ) classical concept of metabolic syndrome including type  2 diabetes as one of the main components . ( b ) proposed concept that type  2 diabetes mellitus is regarded as a major outcome of metabolic syndrome . among the five components of metabolic syndrome , ifg is particularly superior for its ability to predict incident diabetes33 ; the other components can predict cvd better than or similarly to ifg33 . thus , metabolic syndrome with ifg is complimentary , allowing the prediction of cvd and diabetes ; the populations in this group require extra care in management . the role of metabolic syndrome in patients who have been diagnosed with diabetes is a topic many believe should not be ignored . alexander et  al.55 reported that in the usa , over 80% of participants aged 50  years or older with diabetes also have metabolic syndrome . most patients with type  2 diabetes possess multiple risk factors for cvd other than hyperglycemia . because cvd is the leading cause of death in diabetic patients56 , careful attention should be exercised with regard to all modifiable risk factors . many clinical studies have confirmed that adequate control of blood pressure and lipid profiles can reduce cardiovascular risk effectively58 . however , diabetes itself is a strong risk factor for cvd , and type  2 diabetes mellitus is wellknown for its similar risks to coronary heart disease61 . consequently , the value of metabolic syndrome in diabetic patients is relatively weak compared with its value in nondiabetic subjects . in conclusion , metabolic syndrome is immensely useful as a clinical tool to predict diabetes and cvd , especially in highrisk groups with metabolic syndrome that includes ifg . exclusion of diabetes mellitus in metabolic syndrome is important to maximize the prevention effect of cvd with preceding diabetes mellitus . further studies are required in several areas , including unified classification , ambiguous pathogenesis , the  syndrome role and the development of a more effective model .
abstractmetabolic syndrome is defined as a cluster of glucose intolerance , hypertension , dyslipidemia and central obesity with insulin resistance as the source of pathogenesis . 
 although several different combinations of criteria have been used to define metabolic syndrome , a recently published consensus recommends the use of ethnicspecific criteria , including waist circumference as an indicator of central obesity , triglyceride and highdensity lipoprotein ( hdl ) cholesterol as indicators of dyslipidemia , and blood pressure greater than 130/85  mmhg . 
 the definition of dysglycemia , and whether central obesity and insulin resistance are essential components remain controversial . 
 regardless of the definition , the prevalence of metabolic syndrome is increasing in western and asian countries , particularly in developing areas undergoing rapid socioenvironmental changes . 
 numerous clinical trials have shown that metabolic syndrome is an important risk factor for cardiovascular disease ( cvd ) , type  2 diabetes mellitus and allcause mortality . 
 therefore , metabolic syndrome might be useful as a practical tool to predict these two major metabolic disorders . 
 comprehensive management of risk factors is very important to the improvement of personal and public health . 
 however , recent studies have focused on the role metabolic syndrome plays as a risk factor for cvd ; its importance in the prediction of incident diabetes is frequently overlooked . in the present review , 
 we summarize the known evidence supporting metabolic syndrome as a predictor for type  2 diabetes mellitus and cvd . 
 additionally , we suggest how metabolic syndrome might be useful in clinical practice , especially for the prediction of diabetes .