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Prevalence ofMetabolic SyndromeAmong HispanicsLatinos ofDiverse Background The HispanicCommunity Health StudyStudy ofLatinosDiabetes Care 2014372391ndash2399 | DOI 102337dc13-2505
OBJECTIVE
Approximately one-third of the adult US population has the metabolic syn-drome Its prevalence is the highest among Hispanic adults but variation byHispanicLatino background is unknown Our objective was to quantify the prev-alence of the metabolic syndrome among men and women 18ndash74 years of age ofdiverse HispanicLatino background
RESEARCH DESIGN AND METHODS
Two-stage area probability sample of households in four US locales yielding16319 adults (52 women) who self-identified as Cuban Dominican MexicanPuerto Rican Central American or South American The metabolic syndrome wasdefined according to the American Heart AssociationNational Heart Lung andBlood Institute 2009 Joint Scientific Statement Themain outcomemeasures wereage-standardized prevalence of the metabolic syndrome per the harmonizedAmerican Heart AssociationNational Heart Lung and Blood Institute definitionand its component abnormalities
RESULTS
The metabolic syndrome was present in 36 of women and 34 of men Differ-ences in the age-standardized prevalence were seen by age sex and HispanicLatino background The prevalence of the metabolic syndrome among those 18ndash44 45ndash64 and 65ndash74 years of age was 23 50 and 62 respectively amongwomen and 25 43 and 55 respectively among men Among women themetabolic syndrome prevalence ranged from 27 in South Americans to 41 inPuerto Ricans Among men prevalences ranged from 27 in South Americans to35 in Cubans In those with the metabolic syndrome abdominal obesity waspresent in 96 of the women compared with 73 of the men more men (73)than women (62) had hyperglycemia
CONCLUSIONS
The burden of cardiometabolic abnormalities is high in HispanicLatinos but variesby age sex and HispanicLatino background HispanicsLatinos are thus at in-creased but modifiable predicted lifetime risk of diabetes and its cardiovascularsequelae
1Department of Epidemiology University ofNorth Carolina at Chapel Hill Chapel Hill NC2Department of Biostatistics University of NorthCarolina at Chapel Hill Chapel Hill NC3Department of Psychology and BehavioralMed-icine Research Center University of MiamiMiami FL4National Institute of Diabetes and Digestive andKidney Diseases National Institutes of HealthBethesda MD5Preventive Medicine Feinberg School of Medi-cine Northwestern University Chicago IL6Department of Epidemiology and PopulationHealth Albert Einstein College of MedicineBronx NY7Department of Psychology SanDiego State Uni-versity San Diego CA8Division of Cardiovascular Sciences NationalHeart Lung and Blood Institute National Insti-tutes of Health Bethesda MD
Corresponding author Gerardo Heiss gerardo_heissuncedu
Received 27 October 2013 and accepted 10March 2014
This article contains Supplementary Data onlineat httpcarediabetesjournalsorglookupsuppldoi102337dc13-2505-DC1
The contents of this article are solely the re-sponsibility of the authors and do not neces-sarily represent the official position of theNational Institutes of Health the US Depart-ment of Health and Human Services or thefederal government
copy 2014 by the American Diabetes AssociationReaders may use this article as long as the workis properly cited the use is educational and notfor profit and the work is not altered
See accompanying articles pp 2081and 2233
Gerardo Heiss1 Michelle L Snyder1
Yanping Teng2 Neil Schneiderman3
Maria M Llabre3 Catherine Cowie4
Mercedes Carnethon5 Robert Kaplan6
Aida Giachello5 Linda Gallo7
Laura Loehr1 and Larissa Aviles-Santa8
Diabetes Care Volume 37 August 2014 2391
CARDIOVASCULA
RANDMETA
BOLIC
RISK
Many areas of the world experience ahigh population burden ofmetabolic ab-normalities collectively known as meta-bolic syndrome (1) Included in thissyndrome are insulin resistance adipos-ity hyperglycemia hyperlipidemia ele-vated blood pressure and a sustainedmild proinflammatory profile (1) Overthe past decade heavier US adultshave gained more adiposity and ethnicdisparities in BMI and waist circumfer-ence have grown (2) BMI in men andwomen as well as waist circumferencein men increased linearly but amongwomen waist circumference increasedat a steeper rate at higher percentilevalues (2)In the context of a widespread obesity
epidemic the cardiometabolic abnor-malities associated with excess weightand ectopic fat deposition are of consid-erable clinical and public health interest(3) since the metabolic syndrome con-fers an elevated risk of the developmentof type 2 diabetes and cardiovascularsequelae and mortality (4ndash6) Basedon a recently harmonized definition ofthe metabolic syndrome (7) the age-adjusted prevalence of metabolic syn-drome in the US is between 34 and39 depending on the thresholdsused to define abdominal adiposityThe highest prevalence of the metabolicsyndrome in the US was observedamong Mexican Americans in the Na-tional Health and Nutrition ExaminationSurvey (NHANES) 1988ndash1994 (8) In thisreport we provide estimates of theprevalence of the metabolic syndromeamong US HispanicLatino individualswho were 18ndash74 years of age werefrom different Hispanic backgroundsand were recruited from randomly se-lected households in 4 of the 10 largestHispanicLatino urban US communitiesby the Hispanic Community HealthStudyStudy of Latinos (HCHSSOL)
RESEARCH DESIGN AND METHODS
The National Institutes of Healthndashsupported HCHSSOL was designed toexamine the prevalence of risk factorsand protective factors for chronic dis-eases and their association with the in-cidence of newly developed diseaseamong HispanicLatinos (httpwwwcsccunceduhchs) The HCHSSOL de-sign and sampling methods have beenpublished (9) Between March 2008and June 2011 16415 self-identified
HispanicLatino persons 18ndash74 years ofage were recruited from randomly se-lected households in the Bronx NewYork San Diego California Chicago Illi-nois and Miami Florida The study wasdesigned to include participants fromCuban Dominican Mexican PuertoRican Central American and South Amer-ican backgrounds in pre-establishedproportions Households were chosenusing a stratified two-stage area proba-bility sample design Census blockgroups were randomly selected in spec-ified geographic areas of each study siteand households were randomly selectedin each sample block group Householdswere screened for eligibility and self-identified HispanicLatino persons 18ndash74 years of age were selected in eachhousehold Oversampling occurred ateach stage (block groups in areas ofhigh concentration of HispanicLatinoshouseholds associated with an HispanicLatino surname and persons 45ndash74 yearsof age at were sampled at rates higherthan younger household members)Sampling weights that reflect the prob-abilities of selection at each stage wereused in the statistical analyses Approvalby institutional review boards was ob-tained at each participating institutionand written informed consent was ob-tained from all study participants
Study MeasurementsAll examinations and interviewer-administered questionnaires were con-ducted by centrally trained and certifiedstudy personnel following a standard-ized protocol which included ongoingquality assurance procedures All studyprotocolmanuals are available at httpwwwcsccunceduhchs Study partici-pants were asked to fast and to abstainfrom smoking 12 h prior to the exami-nation and also to avoid vigorous phys-ical activity on the morning of theexamination Body weight was mea-sured to the nearest 01 kg and heightwas recorded to the nearest centimeterAbdominal girth was measured in dupli-cate using standardized referencepoints Three seated blood pressuremeasurements were obtained after a5-min rest using an oscillometric auto-mated sphygmomanometer The averageof the second and third measurementswas used in these analyses
Blood samples were obtained followinga nontraumatic venipuncture protocol
fresh as well as frozen specimens wereshipped to the HCHSSOL Central Labora-tory for assays and long-term storage HDLcholesterol (HDL-C) was measured by amagnesiumdextran sulfate method andplasma glucose was measured using ahexokinase enzymatic method (RocheDiagnostics Indianapolis IN) Triglycer-ides were measured in serum on aRoche Modular P chemistry analyzerusing a glycerol blanking enzymaticmethod (Roche Diagnostics) The assaymethodologies and their performanceare described in HCHSSOL Manual7 (Addendum at httpwwwcsccunceduhchspublicdocfilterphpstudy=hchsampfilter_type=public)
Participants were asked to bring allprescription and nonprescription medi-cations and supplements taken duringthe preceding 4 weeks to the examina-tion where all preparations and theirconcentrations and units were codedInterviewer-administered question-naires were used to obtain informationon demographic factors education andincome country of origin and genera-tional status length of residence in theUS and language preference
The metabolic syndrome was definedaccording to the American Heart Asso-ciation National Heart Lung and BloodInstitute 2009 Joint Scientific Statement(7) namely subjects had to have threeor more of the following criteria 1)waist circumference $102 cm in menand $88 cm in women 2) triglyceridelevel $150 mgdL 3) HDL-C level 40mgdL in men and50mgdL in women4) blood pressure $130 mmHg systolicandor $85 mmHg diastolic andor thesubject was receiving medication and 5)fasting glucose level$100 mgdL andorthe subject was receiving medication
Statistical AnalysisSummary statistics and their varianceswere weighted to adjust for samplingprobability and nonresponse (9) Meansmedians and prevalence estimates werecomputed by sex and HispanicLatinobackground and were age-standardizedto the year 2010 US population Thefrequency of the component abnormal-ities of the metabolic syndrome alsowas determined All statistical testswere two-sided at a significance levelof 005 Analyses were performed usingSAS version 92 (SAS Institute) andSUDAAN release 1000 (RTI)
2392 Prevalence of Metabolic Syndrome in HispanicsLatinos Diabetes Care Volume 37 August 2014
RESULTS
Of the 39384 sampled individuals whomet eligibility criteria and were se-lected 417 enrolled in the study Af-ter the exclusion of individuals withmissingunderreported Hispanic back-ground (n = 81) or missing covariates(n = 48) 9789 women and 6530 menwere available for these analyses Asshown in Table 1 the mean baselineage was 411 years and was comparablefor all HispanicLatino groups Individu-als of Mexican origin represented closeto 40 of all sampled individualsfollowed by those of Puerto Rican(17) Cuban (14) Central American(11) Dominican (9) and SouthAmerican (7) origin Consistent withnational surveys (10) 77 of theHCHSSOL participants were over-weight (BMI 25ndash299 kgm2) or obese(BMI $30 kgm2)Approximately 77 of the partici-
pants were not born in the US Al-though 57 of the participants hadlived in the US 15 years 75indicated a preference for conductingthe interviews in Spanish About 32of the participants had less than a high
school education 28 had completedhigh school and 38 had more than ahigh school education Educationalachievement did not differ by Hispanicbackground
The age-standardized prevalence ofthe metabolic syndrome was 337(95 CI 322ndash352) in men and 360(95 CI 346ndash374) in women (Table2) The prevalence of the metabolic syn-drome increased steadily with ageoverall and in both men and womenalthough a greater increase with agewas seen in women (P value for interac-tion 0004) Variability in the prevalenceof the metabolic syndrome was seen byHispanicLatino background and by sex(Table 2) The overall prevalence of themetabolic syndrome was highest amongPuerto Ricans (37 not statistically sig-nificantly different from other groupsamong the men) and significantly (P 005) lower among South Americans(27) compared with other HispanicLatino backgroundsoverall and inwomenThe prevalence of the metabolic syn-drome was significantly (P 0005)higher in Puerto Rican women comparedwith Puerto Rican men
Figure 1 displays the prevalence ofthe number of individual cardiometa-bolic abnormalities of the metabolicsyndrome by sex and HispanicLatinobackground Overall South Americansand Dominicans had the lowest preva-lence of individual abnormalities (andthus of the metabolic syndrome)Puerto Rican women had a higher bur-den of metabolic abnormalities com-pared with Puerto Rican men and withwomen of other HispanicLatino back-ground groups (Fig 1) South Americanmen had the lowest prevalence of met-abolic syndrome abnormalities Amongwomen the prevalence of zero onetwo three four and five cardiometa-bolic abnormalities was 135 233273 199 113 and 46 respec-tively The corresponding prevalencesamong men were 207 229 229196 100 and 38 respectively
A characteristic common to bothsexes is the strong association betweenthe number of cardiometabolic abnor-malities and age The prevalence of(all) five cardiometabolic abnormalitieswas 02 in women 18ndash29 years of age10 in women 60ndash69 years of age and14 in women 70ndash74 years of age Con-versely the prevalence of zero cardio-metabolic abnormalities was 27 inwomen 18ndash29 years of age 2 inwomen 60ndash69 years of age and 05in women 70ndash74 years of age This pat-tern was comparable in men in that theprevalence of the five cardiometabolicabnormalities was 08 in men 18ndash29years of age 8 in men 60ndash69 years ofage and 10 inmen 70ndash74 years of ageHowever unlike women the prevalenceof zero cardiometabolic abnormalitieswas 43 in men 18ndash29 years of age6 in men 60ndash69 years of age and 8in men 70ndash74 years of age
The profile of the cardiometabolic ab-normalities among HispanicLatinos dif-fered by sex The most prevalentcomponent of the metabolic syndromein women was abdominal obesity irre-spective of age group (SupplementaryTable 1) Among women the prevalenceof low HDL-C level was higher in those18ndash44 years of age whereas the preva-lences of elevated blood pressure andhyperglycemia were higher in those75ndash74 years of age Prevalences werehigher for hypertriglyceridemia andlow HDL-C level in men 18ndash44 years ofage whereas prevalences were higher
Table 1mdashCharacteristics of the 16319 HCHSSOL study participants included inthis report (HCHSSOL baseline examination 2008ndash2011)
Characteristics Values
Age years (mean) (SE) 411 (025)
Women () 522 6 06
HispanicLatino background N ()Dominican 1457 (89)Central American 1725 (105)Cuban 2343 (143)Mexican 6451 (393)Puerto Rican 2702 (165)South American 1063 (65)Mixedother 497 (30)
BMI ()daggerUnderweightnormal (25 kgm2) 231 6 05Overweight (25ndash299 kgm2) 371 6 06Obese ($30 kgm2) 396 6 07Missing information 02 6 005
Years in the US 15 years () 570 6 11
Not born in the 50 US states () 773 6 08
Preference for Spanish () 749 6 09
Education ()High school 319 6 07High school 279 6 06High school 384 6 08Missing information 18 6 01
Data are N () or 6 SE unless otherwise indicated Unweighted proportions all other valuesdisplayed in this report are weighted for survey design and nonresponse daggerA total of 248 men(37) and 732 women (74) had BMI values 40 kgm2 A total of 130 individuals had BMIvalues 185 kgm2 (1)
carediabetesjournalsorg Heiss and Associates 2393
for e levated blood pressure andhyperglycemia in men 45ndash64 and75ndash74 years of age (SupplementaryTable 2) The degree to which the me-dian value of an individual risk factorwas elevated relative to the thresholdwas greater with increasing age andwith the number of risk factors in menand in women (Supplementary Tables 1and 2)Among participants with the meta-
bolic syndrome 73 of the men and96 of the women had abdominal obe-sity (exceeding waist circumferencethresholds of 102 and 88 cm respec-tively) 73 of men and 59 of womenhad hypertriglyceridemia 67 of menand 75 of women had low HDL-C lev-els 66 of men and 64 of women hadelevated blood pressure or were receiv-ing antihypertensive treatment and73 of men and 62 of women had hy-perglycemia or were receiving hypogly-cemic agents Low HDL-C values wereremarkably common in women 18ndash44years of age with the metabolic syn-drome while both elevated triglyceridelevels and low HDL-C levels were higheramong the men with metabolic syn-drome who were 65 years of ageSome variability in the prevalence of in-dividual cardiometabolic abnormalitiesacross HispanicLatino backgroundswas observed (Fig 2) Among menwith themetabolic syndrome Dominicanshad the lowest prevalence of low HDL-C
compared with men of other HispanicLatino backgrounds except PuertoRicans Among women with the meta-bolic syndrome the prevalence ofabdominal adiposity was high regard-less of HispanicLatino backgroundDominican women had the lowestprevalence of hypertriglyceridemiacompared with other HispanicLatinobackgrounds Mexican women had thehighest prevalence of hypertriglyceride-mia compared with women of otherHispanicLatino backgrounds exceptfor South Americans and had the low-est prevalence of elevated blood pres-sure compared with women of otherHispanicLatino backgrounds
CONCLUSIONS
HispanicsLatinos who are the largestUS minority group experience a highburden of cardiovascular risk factors(11) Obesity the metabolic syndromeand diabetes have been found tobe prevalent in LatinosHispanics atalarming rates but limitations in theavailable data combined with publichealth concerns led to recommen-dations for additional research inHispanicsLatinos to understand therisk profile of this population (12) Weadd to this body of information bydescribing the prevalence of metabolicsyndrome in its harmonized definition(7) among US HispanicLatino adultsof diverse backgrounds
The prevalence of the metabolic syn-drome in the population sampled by theHCHSSOL was 34 in men and 36 inwomen which is comparable to reportsbased on national probability samplesindicating a higher frequency of occur-rence in US Hispanics than in whites(1013) Among HCHSSOL participants21 of men and 14 of women had nocardiometabolic abnormalities 34 ofmen and 36 of women had three ormore cardiometabolic abnormalitiesand 38 of men and 46 of womenhad five or more abnormalities
The remarkable features in these dataare the high proportion of women whomeet the metabolic syndrome criterionof three or more factors in each agestratum by virtue of exceeding thethreshold value for abdominal girththe high median values of waist circum-ference observed and the progressivelylarger increments in median waist val-ues across increasing numbers of riskfactors present This suggests that ab-dominal adiposity is the salient contrib-utor to the metabolic syndrome amongthe women in the HCHSSOL to agreater degree than for example ele-vated blood pressure or the impair-ments in lipid or glucose metabolismthat are often associated with the for-mer A limitation of these data is the lowresponse at the level of the sampledhouseholds which was 335 All esti-mates are adjusted for nonresponse (9)
As is the case for much of the existingresearch on the health status of His-panicLatino groups in the US mostprevious reports on the metabolic syn-drome among Hispanics are based onMexican Americans or a pooled hetero-geneous group of HispanicsLatinos Al-though limited by small numbers a priorreport (14) identified heterogeneity inthe frequency of the metabolic syn-drome and its components in womenby HispanicLatino background As alsoobserved among the women in theHCHSSOL the prevalence of metabolicsyndrome in the New Jersey site ofthe Study of Womenrsquos Health Acrossthe Nation was greatest in Puerto Ricanwomen (48) and was lowest in Domini-can women at this Study of WomenrsquosHealth Across the Nation site (13) al-though the SEs for these estimates wererather large Similar patterns were ob-served in the Multi-Ethnic Study of Ath-erosclerosis in that Dominicanmen and
Table 2mdashAge-standardized prevalence of the metabolic syndrome by HispanicLatino background and sex 2008ndash2011
CharacteristicsAll participants(N = 16319)
Men(N = 6530)
Women(N = 9789)
Overall 350 (340ndash361) 337 (322ndash352) 360 (346ndash374)
HispanicLatino backgroundDominican (n = 1457) 315 (290ndash340) 306 (263ndash352) 322 (289ndash358)Central American (n = 1725) 358 (330ndash387) 326 (285ndash369) 377 (347ndash408)Cuban (n = 2343) 348 (326ndash370) 347 (319ndash376) 349 (320ndash379)Mexican (n = 6451) 350 (332ndash369) 337 (313ndash362) 360 (335ndash386)Puerto Rican (n = 2702) 371 (344ndash399) 326 (287ndash368) 409 (374ndash446)South American (n = 1063) 273 (242ndash307)dagger 270 (223ndash324) 268 (231ndash309)Dagger
Age-groups (years)18ndash29 (n = 2644) 127 (111ndash144) 129 (108ndash153) 124 (103ndash149)30ndash39 (n = 2375) 247 (225ndash271) 271 (236ndash309) 224 (195ndash257)40ndash49 (n = 4194) 367 (345ndash390) 361 (329ndash394) 373 (345ndash401)50ndash59 (n = 4323) 486 (459ndash514) 448 (413ndash484) 516 (482ndash551)60ndash69 (n = 2283) 568 (538ndash598) 523 (477ndash569) 606 (563ndash647)70ndash74 (n = 500) 666 (603ndash723) 580 (496ndash659) 720 (635ndash793)
Data are (95 CI) Values were weighted for survey design and nonresponse and wereage-standardized to the population described by the 2010 US Census Statistically significantdifferences (P 005) were seen between sexes daggerStatistically significant differences (P 005)were seen among HispanicLatino backgrounds overall DaggerStatistically significant differences(P 005) were seen among women
2394 Prevalence of Metabolic Syndrome in HispanicsLatinos Diabetes Care Volume 37 August 2014
women had a lower prevalence ofthe metabolic syndrome than PuertoRicans (15)The Cardiovascular Risk Factor Mul-
tiple Evaluation in Latin America(CARMELA) study (16) compared theprevalence of the metabolic syndromein residents 25ndash64 years of age (averageage 456 11 years) in seven Latin Amer-ican cities between 2003 and 2005(1600 examinees per city) The prev-alence of the metabolic syndrome de-fined according to the Adult TreatmentPanel III criteria age- and sex-adjustedto the sample from each city rangedfrom 14 in Quito Ecuador to 27 inMexico City Mexico For comparisonuse of the Adult Treatment Panel IIIcriteria in the 2003ndash2006 NHANESshowed a prevalence of 33 amongMexican American men and 41 amongMexican American women (13) Among
the sites surveyed by the CARMELAstudy Mexico City had the highest prev-alence of obesity (31) the metabolicsyndrome (27) and diabetes (9)The prevalence of the metabolic syn-drome observed in the HCHSSOL (34in men and 36 in women) is some-what higher than that estimated by theCARMELA study forMexico City and wasnotoriously higher than those observedin Barquisimeto Venezuela Bogota Co-lombia Buenos Aires Argentina LimaPeru Quito Ecuador and SantiagoChile
Other noteworthy findings from theHCHSSOL population are that 96 ofwomen and 73 of men with the meta-bolic syndrome had abdominal obesityusing the conventional 10288 cmthreshold The International DiabetesFederation conceived of the metabolicsyndrome based onwaist circumference
thresholds that differ for race and ethnicgroups and are considerably lower thanthose originally used in the NationalCholesterol Education Program criteriaIn its 2012 scientific statement on healthdisparities in endocrine disorders (17)the Endocrine Society called for thestudy and adoption of ethnic-specificcut points for central obesity to avoidmisclassification and for appropriaterisk management A number of reports(18ndash20) have raised concerns about thethreshold values for waist circumferenceused by the current definitions of abdom-inal obesity particularly as applied toAsian African American Polynesianand HispanicLatino populations Theprevalence of the metabolic syndromeaccording to different waist circumfer-ence thresholds has been publishedbased on NHANES 2003ndash2006 data (10)When less restrictive definitions of
Figure 1mdashPrevalence () of the number of individual cardiometabolic abnormalities in men (A) and women (B) in the HCHSSOL cohort by HispanicLatino background Error bars represent the SE
carediabetesjournalsorg Heiss and Associates 2395
central obesity were used prevalence es-timates increased as expected whereasassociations with cardiometabolic corre-lates were not visibly affectedRecognizing that the risk associated
with a given waist measurement differsacross populations waist circumferencethresholds recommended for ethnicCentral and South American popula-tions in the 2009 consensus Joint Scien-tific Statement (11) are$90 cm for menand $80 cm for women Instead thedata presented in this report are basedon the waist circumference thresholdsfamiliar to clinical practitioners in theUS ($102 cm in men and $88 cm inwomen) and are used as a commonmetric in reports from the NHANES(15) For comparability with studiesbased in other countries we replicatedour analyses using the$90 cm$80 cm
thresholds for men and women respec-tively recommended by the consensusJoint Scientific Statement (11) for ethnicCentral and South American popula-tions (these data are presented in Sup-plementary Table 3)
There have been several attempts toestablish waist circumference cutoff val-ues for abdominal obesity suitable towomen in Latin America drawing onvarious criteria such as detection of di-abetes (21) abnormal carotid artery in-tima media thickness (22) blood lipidprofile and other risk factors (23) andhypertension (24) Based on an area ofvisceral adipose tissue $100 cm2 mea-sured by computed tomography scan atthe 5th lumbar vertebra Aschner et al(25) recommended 94 cm for men and90 cm for women as the threshold ofabdominal obesity We examined the
impact of waist circumference thresholdvalues recommended by various au-thors for HispanicLatino populationson the prevalence of the metabolic syn-drome in the HCHSSOL populationsOverall their impact on the prevalenceof the metabolic syndrome in women inthe HCHSSOL was minor For examplethe use of the 90 cm threshold (insteadof 88 cm) as recommended by Aschneret al (25) reduced the prevalence of themetabolic syndrome in the women ofthe HCHSSOL samples by only 1ndash2
Various names and definitions havebeen applied to themetabolic syndromesince its original description by Reaven(26) as a cluster of metabolic risk factorsrelated to insulin resistance There isconsensus at this time that insulin resis-tance underlies the clustering of meta-bolic syndrome abnormalities and that
Figure 2mdashPrevalence () of individual cardiometabolic abnormalities in men (A) and women (B) with the metabolic syndrome in the HCHSSOLcohort by HispanicLatino background Error bars represent the SE
2396 Prevalence of Metabolic Syndrome in HispanicsLatinos Diabetes Care Volume 37 August 2014
these are associated with an increasedrisk of type 2 diabetes and cardiovascu-lar sequelae (7) Such associations arewell-established for the individual com-ponents of this syndrome regardless ofwhether they occur in isolation in com-bination or as a qualitatively definedsyndrome based on any three cardio-metabolic abnormalities Although themetabolic syndrome is embedded inclinical management guidelines thereis no consensus about the value of themetabolic syndrome as a tool to screenfor future risk of type 2 diabetes or car-diovascular diseases Whether thecardiometabolic risk factors that con-stitute the metabolic syndrome occuralone or in clusters evidence indicatesthat all such risk factors should be ad-dressed individually and managedeffectively (27) To our knowledge noevidence has been put forward to datefor nonadditivity of these metabolicfactors on the risk of type 2 diabetesincident cardiovascular disease ormortality (ie that the risk associatedwith the metabolic syndrome exceedsthe risk conferred by the sum of theindividual cardiometabolic risk factorsthat contributes to the syndrome)(27ndash29)To aid in the interpretation of waist
circumference Lemieux et al (30) pro-posed the concurrent measurement offasting triglycerides as an inexpensivemeans to screen for the atherogenicmetabolic dysregulation triad charac-terized by hyperinsulinemia elevatedapolipoprotein B level and small denseLDL-C In the HCHSSOL data fastingtriglyceride levels HDL-C levels systolicblood pressure and fasting glucoselevels each were associated with waistcircumference in a monotonically in-creasing (graded) linear fashion with-out indications of an inflection pointor a threshold for waist circumference(data not shown)As a qualitative approach to the
characterization of cardiometabolic ab-normalities associatedwith insulin resis-tance the metabolic syndrome hasbeen endorsed by major professionaland scientific organizations (7) Al-though the Endocrine Society endorsedthe use of the metabolic syndrome inclinical practice guidelines as a toolfor primary prevention of type 2 diabe-tes and cardiovascular disease its rel-evance still is subject to disagreement
(31) The lack of management or ther-apies specific to this syndromedasopposed to its individual componentabnormalitiesdmakes its use in clini-cal settings counterintuitive and theneed for sex- race- and ethnic group-specific thresholds for abdominal adi-posity for a ldquouniversalrdquo definition ofthe metabolic syndrome makes thisconstruct susceptible to misclassifica-tion and remains a source of contro-versy (25)
The metabolic syndrome traits areknown to have high heritability (30ndash70) and candidate gene approacheslinkage studies and genome-wide asso-ciation studies (32) have identified sus-ceptibility regions and loci for individualmetabolic syndrome components Theheritability of the metabolic syndromeis reportedly 30 although little ofthis heritability has been accounted for(33) Evidence for a common genetic un-derpinning of the broad spectrum of themetabolic syndrome has not been forth-coming despite reports from genome-wide association studies of geneticvariants associated with more than one ofthe metabolic abnormalities included inthe metabolic syndrome (34) Althoughwell-conducted studies failed to identifysignificant genetic susceptibility to mul-tiple metabolic syndrome components(35) the modulation of metabolic syn-drome expression by gene 3 environ-ment interactiondsuch as gene 3energy expenditure interaction (36)dwarrants further study
The clustering of metabolic impair-ments and the observed temporaltrends in the prevalence of the meta-bolic syndrome are thought to resultfrom excess food consumption andorreduced levels of physical activity Ex-cess nutrient intake leads to adiposityand activation of stress signaling whichin turn results in chronic activation ofproinflammatory kinase pathways thatdesensitize the metabolic response toinsulin (37) Development of the meta-bolic syndrome in humans is alsothought to be promoted by high levelsof saturated fats supported by animalmodels where high-fat diets inducedmetabolic disease (38) Recent workhas highlighted the role of intestinal mi-crobiota in promoting the cardiometa-bolic abnormalities associated with themetabolic syndrome such as adiposityby increasing the capacity of the host to
extract energy from ingested food (39)or through interaction with the innateimmune system in modulating inflam-matory signaling (40) Murine modelssuggest that the loss of Toll-like receptor5 function in the intestinal mucosachanges gut microbiota that inducelow-grade inflammatory signalingwhich may desensitize insulin receptorsignaling leading to excess food con-sumption and the associated cardiometa-bolic abnormalities of the metabolicsyndrome (40) The excess caloric con-sumption thought to drive the currentepidemic in metabolic syndrome maytherefore be influenced in part by host-microbiota interactions
In conclusion the prevalence of themetabolic syndrome and that of thecardiometabolic abnormalities that areconsidered to be components of themetabolic syndrome is high in His-panicLatinos and varies by sex andacross HispanicLatino backgroundsAbdominal adiposity predominates inHispanicLatino women in men thecharacterization by HispanicLatinobackgrounds shows heterogeneity inthe profiles of the component cardio-metabolic abnormalities The preven-tion of metabolic abnormalities andtheir clinical management may benefitfrom awareness of the diversity in car-diometabolic dysregulation by sex andHispanicLatino background This is re-inforced by the lack of prevention poli-cies or clinical management guidelinesthat are specific to the metabolic syn-drome per se as opposed to its compo-nent factors Efforts to control thepopulation burden of cardio-metabolicrisk among HispanicsLatinos will bene-fit from the observed differences by sexand HispanicLatino backgrounds
Acknowledgments The authors thank theHispanic Community Health StudyStudy ofLatinos (HCHSSOL) participants who gener-ously contributed their time and provided thestudy data The authors also thank the HCHSSOL staff members for their dedication andexpertise A complete list of staff and inves-tigators was published in the Annals of Epide-miology 201020642ndash649 and is also availableon the study website (httpwwwcsccunceduhchs)Funding The Hispanic Community HealthStudyStudy of Latinos (HCHSSOL) was carriedout as a collaborative study supported bycontracts from the National Heart Lung andBlood Institute (NHLBI) to the University ofNorth Carolina (N01-HC65233) the University
carediabetesjournalsorg Heiss and Associates 2397
of Miami (N01-HC65234) Albert Einstein Col-lege of Medicine (N01-HC65235) NorthwesternUniversity (N01-HC65236) and San Diego StateUniversity (N01-HC65237) The following insti-tutes centers or offices contribute to theHCHSSOL through a transfer of funds to theNHLBI National Center on Minority Health andHealth Disparities the National Institute onDeafness and Other Communication Disordersthe National Institute of Dental and CraniofacialResearch the National Institute of Diabetes andDigestive and Kidney Diseases the NationalInstitute of Neurological Disorders and Strokeand the Office of Dietary Supplements
The funding agency had a role in the design andconduct of the study in the collection analysisand interpretation of the data and in the reviewand approval of the manuscriptDuality of Interest No potential conflicts ofinterest relevant to this article were reportedAuthors Contributions GH researched theliterature interpreted the data and organizedand wrote the manuscript MLS NS MMLCC MC RK AG LG LL and LA-Scontributed to the interpretation of the dataand to the writing of the manuscript and wereinvolved in editing during manuscript prepara-tion YT conducted the statistical analysesprovided comments and had oversight of theverification of results GH is the guarantorof this work and as such had full access to allthe data in the study and takes responsibility forthe integrity of the data and the accuracy of thedata analysisPrior Presentation A set of preliminary datafrom this study was presented at the Epidemi-ology and PreventionNutrition Physical Activ-ity and Metabolism 2013 Scientific Sessions ofthe American Heart AssociationAmericanStroke Association New Orleans LA 19ndash22March 2013
References1 Hossain P Kawar B El Nahas M Obesity anddiabetes in the developing worldda growingchallenge N Engl J Med 2007356213ndash2152 BeydounMA Wang Y Gender-ethnic dispar-ity in BMI and waist circumference distributionshifts in US adults Obesity (Silver Spring) 200917169ndash1763 Olshansky SJ Passaro DJ Hershow RC et alA potential decline in life expectancy in theUnited States in the 21st century N Engl JMed 20053521138ndash11454 Ford ES Li C Sattar N Metabolic syndromeand incident diabetes current state of the evi-dence Diabetes Care 2008311898ndash19045 Ballantyne CM Hoogeveen RC McNeill AMet al Metabolic syndrome risk for cardiovascu-lar disease and diabetes in the ARIC study Int JObes (Lond) 200832(Suppl 2)S21ndashS246 Lakka HM Laaksonen DE Lakka TA et al Themetabolic syndrome and total and cardiovascu-lar disease mortality in middle-aged men JAMA20022882709ndash27167 Alberti KG Eckel RH Grundy SM et al In-ternational Diabetes Federation Task Force onEpidemiology and Prevention National HeartLung and Blood Institute American HeartAssociation World Heart Federation Interna-tional Atherosclerosis Society International As-sociation for the Study of Obesity Harmonizing
the metabolic syndrome a joint interim state-ment of the International Diabetes Federationtask force on epidemiology and prevention Na-tional Heart Lung and Blood Institute Ameri-can Heart Association World Heart FederationInternational Atherosclerosis Society and In-ternational Association for the Study of Obe-sity Circulation 20091201640ndash16458 Ford ES Giles WH Dietz WH Prevalence ofthe metabolic syndrome among US adultsfindings from the third National Health and Nu-trition Examination Survey JAMA 2002287356ndash3599 Lavange LM Kalsbeek WD Sorlie PD et alSample design and cohort selection in the His-panic Community Health StudyStudy of Lati-nos Ann Epidemiol 201020642ndash64910 Ford ES Li C Zhao G Prevalence and corre-lates of metabolic syndrome based on a harmo-nious definition among adults in the USJ Diabetes 20102180ndash19311 Daviglus ML Talavera GA Aviles-Santa MLet al Prevalence of major cardiovascular riskfactors and cardiovascular diseases among His-panicLatino individuals of diverse backgroundsin the United States JAMA 20123081775ndash178412 Davidson JA Kannel WB Lopez-Candales Aet al Avoiding the looming LatinoHispanic car-diovascular health crisis a call to action EthnDis 200717568ndash57313 Ervin RB Prevalence of metabolic syn-drome among adults 20 years of age and overby sex age race and ethnicity and body massindex United States 2003-2006 Natl HealthStat Rep 20091ndash714 Derby CA Wildman RP McGinn AP et alCardiovascular risk factor variation within a His-panic cohort SWAN the Study of WomenrsquosHealth Across the Nation Ethn Dis 201020396ndash40215 Allison MA Budoff MJ Wong NDBlumenthal RS Schreiner PJ Criqui MH Prev-alence of and risk factors for subclinical car-diovascular disease in selected US Hispanicethnic groups the Multi-Ethnic Study of Ath-erosclerosis Am J Epidemiol 2008167962ndash96916 Schargrodsky H Hernandez-Hernandez RChampagne BM et al CARMELA Study Investi-gators CARMELA assessment of cardiovascularrisk in seven Latin American cities Am J Med200812158ndash6517 Golden SH Brown A Cauley JA et al Healthdisparities in endocrine disorders biologicalclinical and nonclinical factorsdan EndocrineSociety scientific statement J Clin EndocrinolMetab 201297E1579ndashE163918 Katzmarzyk PT Bray GA Greenway FL et alEthnic-specific BMI and waist circumferencethresholds Obesity (Silver Spring) 2011191272ndash127819 Palaniappan LPWong EC Shin JJ FortmannSP Lauderdale DS Asian Americans havegreater prevalence of metabolic syndrome de-spite lower body mass index Int J Obes (Lond)201135393ndash40020 Sumner AE Sen S Ricks M Frempong BASebring NG Kushner H Determining the waistcircumference in African Americans which bestpredicts insulin resistance Obesity (SilverSpring) 200816841ndash846
21 Barbosa PJ Lessa I de Almeida Filho NMagalhatildees LB Araujo J Criteria for centralobesity in a Brazilian population impact onmet-abolic syndrome Arq Bras Cardiol 200687407ndash41422 Medina-Lezama J Pastorius CA Zea-Diaz Het al PREVENCION Investigators Optimal defini-tions for abdominal obesity and the metabolicsyndrome in Andean Hispanics the PREVENCIONstudy Diabetes Care 2010331385ndash138823 Perez M Casas JP Cubillos-Garzon LA et alUsing waist circumference as a screening tool toidentify Colombian subjects at cardiovascularrisk Eur J Cardiovasc Prev Rehabil 200310328ndash33524 Sanchez-Castillo CP Velazquez-Monroy OBerber A Lara-Esqueda A Tapia-Conyer RJames WP Encuesta Nacional de Salud (ENSA)2000 Working Group Anthropometric cutoffpoints for predicting chronic diseases in theMexican National Health Survey 2000 ObesRes 200311442ndash45125 Aschner P Buendıa R Brajkovich I et alDetermination of the cutoff point for waist cir-cumference that establishes the presence of ab-dominal obesity in Latin American men andwomen Diabetes Res Clin Pract 201193243ndash24726 Reaven GM Banting lecture 1988 Role ofinsulin resistance in human disease Diabetes1988371595ndash160727 Kahn R Buse J Ferrannini E SternM Amer-ican Diabetes Association European Associa-tion for the Study of Diabetes The metabolicsyndrome time for a critical appraisal jointstatement from the American Diabetes Associ-ation and the European Association for theStudy of Diabetes Diabetes Care 2005282289ndash230428 Grundy SM Metabolic syndrome pan-demic Arterioscler Thromb Vasc Biol 200828629ndash63629 Bruno G Fornengo P Segre O et al What isthe clinical usefulness of the metabolic syn-drome The Casale Monferrato study J Hyper-tens 2009272403ndash240830 Lemieux I Pascot A Couillard C et al Hy-pertriglyceridemic waist a marker of the ath-erogenic metabolic triad (hyperinsulinemiahyperapolipoprotein B small dense LDL) inmen Circulation 2000102179ndash18431 Rosenzweig JL Ferrannini E Grundy SMet al Endocrine Society Primary preventionof cardiovascular disease and type 2 diabetesin patients at metabolic risk an endocrine soci-ety clinical practice guideline J Clin EndocrinolMetab 2008933671ndash368932 Aguilera CM Olza J Gil A Genetic suscep-tibility to obesity and metabolic syndrome inchildhood Nutr Hosp 201328(Suppl 5)44ndash5533 Benyamin B Soslashrensen TI Schousboe KFenger M Visscher PM Kyvik KO Are therecommon genetic and environmental factors be-hind the endophenotypes associated with themetabolic syndrome Diabetologia 2007501880ndash188834 Dastani Z Hivert MF Timpson N et alNovel loci for adiponectin levels and their influ-ence on type 2 diabetes and metabolic traitsa multi-ethnic meta-analysis of 45891 individu-als PLoS Genet 20128e1002607
2398 Prevalence of Metabolic Syndrome in HispanicsLatinos Diabetes Care Volume 37 August 2014
35 Kristiansson K Perola M Tikkanen E et alGenome-wide screen for metabolic syndromesusceptibility loci reveals strong lipid genecontribution but no evidence for common ge-netic basis for clustering of metabolic syn-drome traits Circ Cardiovasc Genet 20125242ndash24936 Santos DM Katzmarzyk PT Diego VP et alGenotype by energy expenditure interaction
with metabolic syndrome traits the Portuguesehealthy family study PLoS One 20138e8041737 Hotamisligil GS Erbay E Nutrient sensingand inflammation in metabolic diseases NatRev Immunol 20088923ndash93438 Cani PDBibiloni R KnaufC et al Changes in gutmicrobiota control metabolic endotoxemia-inducedinflammation in high-fat diet-induced obesity anddiabetes in mice Diabetes 2008571470ndash1481
39 Turnbaugh PJ Ley RE Mahowald MAMagrini V Mardis ER Gordon JI An obesity-associated gut microbiome with increased ca-pacity for energy harvest Nature 20064441027ndash103140 Vijay-Kumar M Aitken JD Carvalho FAet al Metabolic syndrome and altered gut mi-crobiota in mice lacking Toll-like receptor 5 Sci-ence 2010328228ndash231
carediabetesjournalsorg Heiss and Associates 2399
Many areas of the world experience ahigh population burden ofmetabolic ab-normalities collectively known as meta-bolic syndrome (1) Included in thissyndrome are insulin resistance adipos-ity hyperglycemia hyperlipidemia ele-vated blood pressure and a sustainedmild proinflammatory profile (1) Overthe past decade heavier US adultshave gained more adiposity and ethnicdisparities in BMI and waist circumfer-ence have grown (2) BMI in men andwomen as well as waist circumferencein men increased linearly but amongwomen waist circumference increasedat a steeper rate at higher percentilevalues (2)In the context of a widespread obesity
epidemic the cardiometabolic abnor-malities associated with excess weightand ectopic fat deposition are of consid-erable clinical and public health interest(3) since the metabolic syndrome con-fers an elevated risk of the developmentof type 2 diabetes and cardiovascularsequelae and mortality (4ndash6) Basedon a recently harmonized definition ofthe metabolic syndrome (7) the age-adjusted prevalence of metabolic syn-drome in the US is between 34 and39 depending on the thresholdsused to define abdominal adiposityThe highest prevalence of the metabolicsyndrome in the US was observedamong Mexican Americans in the Na-tional Health and Nutrition ExaminationSurvey (NHANES) 1988ndash1994 (8) In thisreport we provide estimates of theprevalence of the metabolic syndromeamong US HispanicLatino individualswho were 18ndash74 years of age werefrom different Hispanic backgroundsand were recruited from randomly se-lected households in 4 of the 10 largestHispanicLatino urban US communitiesby the Hispanic Community HealthStudyStudy of Latinos (HCHSSOL)
RESEARCH DESIGN AND METHODS
The National Institutes of Healthndashsupported HCHSSOL was designed toexamine the prevalence of risk factorsand protective factors for chronic dis-eases and their association with the in-cidence of newly developed diseaseamong HispanicLatinos (httpwwwcsccunceduhchs) The HCHSSOL de-sign and sampling methods have beenpublished (9) Between March 2008and June 2011 16415 self-identified
HispanicLatino persons 18ndash74 years ofage were recruited from randomly se-lected households in the Bronx NewYork San Diego California Chicago Illi-nois and Miami Florida The study wasdesigned to include participants fromCuban Dominican Mexican PuertoRican Central American and South Amer-ican backgrounds in pre-establishedproportions Households were chosenusing a stratified two-stage area proba-bility sample design Census blockgroups were randomly selected in spec-ified geographic areas of each study siteand households were randomly selectedin each sample block group Householdswere screened for eligibility and self-identified HispanicLatino persons 18ndash74 years of age were selected in eachhousehold Oversampling occurred ateach stage (block groups in areas ofhigh concentration of HispanicLatinoshouseholds associated with an HispanicLatino surname and persons 45ndash74 yearsof age at were sampled at rates higherthan younger household members)Sampling weights that reflect the prob-abilities of selection at each stage wereused in the statistical analyses Approvalby institutional review boards was ob-tained at each participating institutionand written informed consent was ob-tained from all study participants
Study MeasurementsAll examinations and interviewer-administered questionnaires were con-ducted by centrally trained and certifiedstudy personnel following a standard-ized protocol which included ongoingquality assurance procedures All studyprotocolmanuals are available at httpwwwcsccunceduhchs Study partici-pants were asked to fast and to abstainfrom smoking 12 h prior to the exami-nation and also to avoid vigorous phys-ical activity on the morning of theexamination Body weight was mea-sured to the nearest 01 kg and heightwas recorded to the nearest centimeterAbdominal girth was measured in dupli-cate using standardized referencepoints Three seated blood pressuremeasurements were obtained after a5-min rest using an oscillometric auto-mated sphygmomanometer The averageof the second and third measurementswas used in these analyses
Blood samples were obtained followinga nontraumatic venipuncture protocol
fresh as well as frozen specimens wereshipped to the HCHSSOL Central Labora-tory for assays and long-term storage HDLcholesterol (HDL-C) was measured by amagnesiumdextran sulfate method andplasma glucose was measured using ahexokinase enzymatic method (RocheDiagnostics Indianapolis IN) Triglycer-ides were measured in serum on aRoche Modular P chemistry analyzerusing a glycerol blanking enzymaticmethod (Roche Diagnostics) The assaymethodologies and their performanceare described in HCHSSOL Manual7 (Addendum at httpwwwcsccunceduhchspublicdocfilterphpstudy=hchsampfilter_type=public)
Participants were asked to bring allprescription and nonprescription medi-cations and supplements taken duringthe preceding 4 weeks to the examina-tion where all preparations and theirconcentrations and units were codedInterviewer-administered question-naires were used to obtain informationon demographic factors education andincome country of origin and genera-tional status length of residence in theUS and language preference
The metabolic syndrome was definedaccording to the American Heart Asso-ciation National Heart Lung and BloodInstitute 2009 Joint Scientific Statement(7) namely subjects had to have threeor more of the following criteria 1)waist circumference $102 cm in menand $88 cm in women 2) triglyceridelevel $150 mgdL 3) HDL-C level 40mgdL in men and50mgdL in women4) blood pressure $130 mmHg systolicandor $85 mmHg diastolic andor thesubject was receiving medication and 5)fasting glucose level$100 mgdL andorthe subject was receiving medication
Statistical AnalysisSummary statistics and their varianceswere weighted to adjust for samplingprobability and nonresponse (9) Meansmedians and prevalence estimates werecomputed by sex and HispanicLatinobackground and were age-standardizedto the year 2010 US population Thefrequency of the component abnormal-ities of the metabolic syndrome alsowas determined All statistical testswere two-sided at a significance levelof 005 Analyses were performed usingSAS version 92 (SAS Institute) andSUDAAN release 1000 (RTI)
2392 Prevalence of Metabolic Syndrome in HispanicsLatinos Diabetes Care Volume 37 August 2014
RESULTS
Of the 39384 sampled individuals whomet eligibility criteria and were se-lected 417 enrolled in the study Af-ter the exclusion of individuals withmissingunderreported Hispanic back-ground (n = 81) or missing covariates(n = 48) 9789 women and 6530 menwere available for these analyses Asshown in Table 1 the mean baselineage was 411 years and was comparablefor all HispanicLatino groups Individu-als of Mexican origin represented closeto 40 of all sampled individualsfollowed by those of Puerto Rican(17) Cuban (14) Central American(11) Dominican (9) and SouthAmerican (7) origin Consistent withnational surveys (10) 77 of theHCHSSOL participants were over-weight (BMI 25ndash299 kgm2) or obese(BMI $30 kgm2)Approximately 77 of the partici-
pants were not born in the US Al-though 57 of the participants hadlived in the US 15 years 75indicated a preference for conductingthe interviews in Spanish About 32of the participants had less than a high
school education 28 had completedhigh school and 38 had more than ahigh school education Educationalachievement did not differ by Hispanicbackground
The age-standardized prevalence ofthe metabolic syndrome was 337(95 CI 322ndash352) in men and 360(95 CI 346ndash374) in women (Table2) The prevalence of the metabolic syn-drome increased steadily with ageoverall and in both men and womenalthough a greater increase with agewas seen in women (P value for interac-tion 0004) Variability in the prevalenceof the metabolic syndrome was seen byHispanicLatino background and by sex(Table 2) The overall prevalence of themetabolic syndrome was highest amongPuerto Ricans (37 not statistically sig-nificantly different from other groupsamong the men) and significantly (P 005) lower among South Americans(27) compared with other HispanicLatino backgroundsoverall and inwomenThe prevalence of the metabolic syn-drome was significantly (P 0005)higher in Puerto Rican women comparedwith Puerto Rican men
Figure 1 displays the prevalence ofthe number of individual cardiometa-bolic abnormalities of the metabolicsyndrome by sex and HispanicLatinobackground Overall South Americansand Dominicans had the lowest preva-lence of individual abnormalities (andthus of the metabolic syndrome)Puerto Rican women had a higher bur-den of metabolic abnormalities com-pared with Puerto Rican men and withwomen of other HispanicLatino back-ground groups (Fig 1) South Americanmen had the lowest prevalence of met-abolic syndrome abnormalities Amongwomen the prevalence of zero onetwo three four and five cardiometa-bolic abnormalities was 135 233273 199 113 and 46 respec-tively The corresponding prevalencesamong men were 207 229 229196 100 and 38 respectively
A characteristic common to bothsexes is the strong association betweenthe number of cardiometabolic abnor-malities and age The prevalence of(all) five cardiometabolic abnormalitieswas 02 in women 18ndash29 years of age10 in women 60ndash69 years of age and14 in women 70ndash74 years of age Con-versely the prevalence of zero cardio-metabolic abnormalities was 27 inwomen 18ndash29 years of age 2 inwomen 60ndash69 years of age and 05in women 70ndash74 years of age This pat-tern was comparable in men in that theprevalence of the five cardiometabolicabnormalities was 08 in men 18ndash29years of age 8 in men 60ndash69 years ofage and 10 inmen 70ndash74 years of ageHowever unlike women the prevalenceof zero cardiometabolic abnormalitieswas 43 in men 18ndash29 years of age6 in men 60ndash69 years of age and 8in men 70ndash74 years of age
The profile of the cardiometabolic ab-normalities among HispanicLatinos dif-fered by sex The most prevalentcomponent of the metabolic syndromein women was abdominal obesity irre-spective of age group (SupplementaryTable 1) Among women the prevalenceof low HDL-C level was higher in those18ndash44 years of age whereas the preva-lences of elevated blood pressure andhyperglycemia were higher in those75ndash74 years of age Prevalences werehigher for hypertriglyceridemia andlow HDL-C level in men 18ndash44 years ofage whereas prevalences were higher
Table 1mdashCharacteristics of the 16319 HCHSSOL study participants included inthis report (HCHSSOL baseline examination 2008ndash2011)
Characteristics Values
Age years (mean) (SE) 411 (025)
Women () 522 6 06
HispanicLatino background N ()Dominican 1457 (89)Central American 1725 (105)Cuban 2343 (143)Mexican 6451 (393)Puerto Rican 2702 (165)South American 1063 (65)Mixedother 497 (30)
BMI ()daggerUnderweightnormal (25 kgm2) 231 6 05Overweight (25ndash299 kgm2) 371 6 06Obese ($30 kgm2) 396 6 07Missing information 02 6 005
Years in the US 15 years () 570 6 11
Not born in the 50 US states () 773 6 08
Preference for Spanish () 749 6 09
Education ()High school 319 6 07High school 279 6 06High school 384 6 08Missing information 18 6 01
Data are N () or 6 SE unless otherwise indicated Unweighted proportions all other valuesdisplayed in this report are weighted for survey design and nonresponse daggerA total of 248 men(37) and 732 women (74) had BMI values 40 kgm2 A total of 130 individuals had BMIvalues 185 kgm2 (1)
carediabetesjournalsorg Heiss and Associates 2393
for e levated blood pressure andhyperglycemia in men 45ndash64 and75ndash74 years of age (SupplementaryTable 2) The degree to which the me-dian value of an individual risk factorwas elevated relative to the thresholdwas greater with increasing age andwith the number of risk factors in menand in women (Supplementary Tables 1and 2)Among participants with the meta-
bolic syndrome 73 of the men and96 of the women had abdominal obe-sity (exceeding waist circumferencethresholds of 102 and 88 cm respec-tively) 73 of men and 59 of womenhad hypertriglyceridemia 67 of menand 75 of women had low HDL-C lev-els 66 of men and 64 of women hadelevated blood pressure or were receiv-ing antihypertensive treatment and73 of men and 62 of women had hy-perglycemia or were receiving hypogly-cemic agents Low HDL-C values wereremarkably common in women 18ndash44years of age with the metabolic syn-drome while both elevated triglyceridelevels and low HDL-C levels were higheramong the men with metabolic syn-drome who were 65 years of ageSome variability in the prevalence of in-dividual cardiometabolic abnormalitiesacross HispanicLatino backgroundswas observed (Fig 2) Among menwith themetabolic syndrome Dominicanshad the lowest prevalence of low HDL-C
compared with men of other HispanicLatino backgrounds except PuertoRicans Among women with the meta-bolic syndrome the prevalence ofabdominal adiposity was high regard-less of HispanicLatino backgroundDominican women had the lowestprevalence of hypertriglyceridemiacompared with other HispanicLatinobackgrounds Mexican women had thehighest prevalence of hypertriglyceride-mia compared with women of otherHispanicLatino backgrounds exceptfor South Americans and had the low-est prevalence of elevated blood pres-sure compared with women of otherHispanicLatino backgrounds
CONCLUSIONS
HispanicsLatinos who are the largestUS minority group experience a highburden of cardiovascular risk factors(11) Obesity the metabolic syndromeand diabetes have been found tobe prevalent in LatinosHispanics atalarming rates but limitations in theavailable data combined with publichealth concerns led to recommen-dations for additional research inHispanicsLatinos to understand therisk profile of this population (12) Weadd to this body of information bydescribing the prevalence of metabolicsyndrome in its harmonized definition(7) among US HispanicLatino adultsof diverse backgrounds
The prevalence of the metabolic syn-drome in the population sampled by theHCHSSOL was 34 in men and 36 inwomen which is comparable to reportsbased on national probability samplesindicating a higher frequency of occur-rence in US Hispanics than in whites(1013) Among HCHSSOL participants21 of men and 14 of women had nocardiometabolic abnormalities 34 ofmen and 36 of women had three ormore cardiometabolic abnormalitiesand 38 of men and 46 of womenhad five or more abnormalities
The remarkable features in these dataare the high proportion of women whomeet the metabolic syndrome criterionof three or more factors in each agestratum by virtue of exceeding thethreshold value for abdominal girththe high median values of waist circum-ference observed and the progressivelylarger increments in median waist val-ues across increasing numbers of riskfactors present This suggests that ab-dominal adiposity is the salient contrib-utor to the metabolic syndrome amongthe women in the HCHSSOL to agreater degree than for example ele-vated blood pressure or the impair-ments in lipid or glucose metabolismthat are often associated with the for-mer A limitation of these data is the lowresponse at the level of the sampledhouseholds which was 335 All esti-mates are adjusted for nonresponse (9)
As is the case for much of the existingresearch on the health status of His-panicLatino groups in the US mostprevious reports on the metabolic syn-drome among Hispanics are based onMexican Americans or a pooled hetero-geneous group of HispanicsLatinos Al-though limited by small numbers a priorreport (14) identified heterogeneity inthe frequency of the metabolic syn-drome and its components in womenby HispanicLatino background As alsoobserved among the women in theHCHSSOL the prevalence of metabolicsyndrome in the New Jersey site ofthe Study of Womenrsquos Health Acrossthe Nation was greatest in Puerto Ricanwomen (48) and was lowest in Domini-can women at this Study of WomenrsquosHealth Across the Nation site (13) al-though the SEs for these estimates wererather large Similar patterns were ob-served in the Multi-Ethnic Study of Ath-erosclerosis in that Dominicanmen and
Table 2mdashAge-standardized prevalence of the metabolic syndrome by HispanicLatino background and sex 2008ndash2011
CharacteristicsAll participants(N = 16319)
Men(N = 6530)
Women(N = 9789)
Overall 350 (340ndash361) 337 (322ndash352) 360 (346ndash374)
HispanicLatino backgroundDominican (n = 1457) 315 (290ndash340) 306 (263ndash352) 322 (289ndash358)Central American (n = 1725) 358 (330ndash387) 326 (285ndash369) 377 (347ndash408)Cuban (n = 2343) 348 (326ndash370) 347 (319ndash376) 349 (320ndash379)Mexican (n = 6451) 350 (332ndash369) 337 (313ndash362) 360 (335ndash386)Puerto Rican (n = 2702) 371 (344ndash399) 326 (287ndash368) 409 (374ndash446)South American (n = 1063) 273 (242ndash307)dagger 270 (223ndash324) 268 (231ndash309)Dagger
Age-groups (years)18ndash29 (n = 2644) 127 (111ndash144) 129 (108ndash153) 124 (103ndash149)30ndash39 (n = 2375) 247 (225ndash271) 271 (236ndash309) 224 (195ndash257)40ndash49 (n = 4194) 367 (345ndash390) 361 (329ndash394) 373 (345ndash401)50ndash59 (n = 4323) 486 (459ndash514) 448 (413ndash484) 516 (482ndash551)60ndash69 (n = 2283) 568 (538ndash598) 523 (477ndash569) 606 (563ndash647)70ndash74 (n = 500) 666 (603ndash723) 580 (496ndash659) 720 (635ndash793)
Data are (95 CI) Values were weighted for survey design and nonresponse and wereage-standardized to the population described by the 2010 US Census Statistically significantdifferences (P 005) were seen between sexes daggerStatistically significant differences (P 005)were seen among HispanicLatino backgrounds overall DaggerStatistically significant differences(P 005) were seen among women
2394 Prevalence of Metabolic Syndrome in HispanicsLatinos Diabetes Care Volume 37 August 2014
women had a lower prevalence ofthe metabolic syndrome than PuertoRicans (15)The Cardiovascular Risk Factor Mul-
tiple Evaluation in Latin America(CARMELA) study (16) compared theprevalence of the metabolic syndromein residents 25ndash64 years of age (averageage 456 11 years) in seven Latin Amer-ican cities between 2003 and 2005(1600 examinees per city) The prev-alence of the metabolic syndrome de-fined according to the Adult TreatmentPanel III criteria age- and sex-adjustedto the sample from each city rangedfrom 14 in Quito Ecuador to 27 inMexico City Mexico For comparisonuse of the Adult Treatment Panel IIIcriteria in the 2003ndash2006 NHANESshowed a prevalence of 33 amongMexican American men and 41 amongMexican American women (13) Among
the sites surveyed by the CARMELAstudy Mexico City had the highest prev-alence of obesity (31) the metabolicsyndrome (27) and diabetes (9)The prevalence of the metabolic syn-drome observed in the HCHSSOL (34in men and 36 in women) is some-what higher than that estimated by theCARMELA study forMexico City and wasnotoriously higher than those observedin Barquisimeto Venezuela Bogota Co-lombia Buenos Aires Argentina LimaPeru Quito Ecuador and SantiagoChile
Other noteworthy findings from theHCHSSOL population are that 96 ofwomen and 73 of men with the meta-bolic syndrome had abdominal obesityusing the conventional 10288 cmthreshold The International DiabetesFederation conceived of the metabolicsyndrome based onwaist circumference
thresholds that differ for race and ethnicgroups and are considerably lower thanthose originally used in the NationalCholesterol Education Program criteriaIn its 2012 scientific statement on healthdisparities in endocrine disorders (17)the Endocrine Society called for thestudy and adoption of ethnic-specificcut points for central obesity to avoidmisclassification and for appropriaterisk management A number of reports(18ndash20) have raised concerns about thethreshold values for waist circumferenceused by the current definitions of abdom-inal obesity particularly as applied toAsian African American Polynesianand HispanicLatino populations Theprevalence of the metabolic syndromeaccording to different waist circumfer-ence thresholds has been publishedbased on NHANES 2003ndash2006 data (10)When less restrictive definitions of
Figure 1mdashPrevalence () of the number of individual cardiometabolic abnormalities in men (A) and women (B) in the HCHSSOL cohort by HispanicLatino background Error bars represent the SE
carediabetesjournalsorg Heiss and Associates 2395
central obesity were used prevalence es-timates increased as expected whereasassociations with cardiometabolic corre-lates were not visibly affectedRecognizing that the risk associated
with a given waist measurement differsacross populations waist circumferencethresholds recommended for ethnicCentral and South American popula-tions in the 2009 consensus Joint Scien-tific Statement (11) are$90 cm for menand $80 cm for women Instead thedata presented in this report are basedon the waist circumference thresholdsfamiliar to clinical practitioners in theUS ($102 cm in men and $88 cm inwomen) and are used as a commonmetric in reports from the NHANES(15) For comparability with studiesbased in other countries we replicatedour analyses using the$90 cm$80 cm
thresholds for men and women respec-tively recommended by the consensusJoint Scientific Statement (11) for ethnicCentral and South American popula-tions (these data are presented in Sup-plementary Table 3)
There have been several attempts toestablish waist circumference cutoff val-ues for abdominal obesity suitable towomen in Latin America drawing onvarious criteria such as detection of di-abetes (21) abnormal carotid artery in-tima media thickness (22) blood lipidprofile and other risk factors (23) andhypertension (24) Based on an area ofvisceral adipose tissue $100 cm2 mea-sured by computed tomography scan atthe 5th lumbar vertebra Aschner et al(25) recommended 94 cm for men and90 cm for women as the threshold ofabdominal obesity We examined the
impact of waist circumference thresholdvalues recommended by various au-thors for HispanicLatino populationson the prevalence of the metabolic syn-drome in the HCHSSOL populationsOverall their impact on the prevalenceof the metabolic syndrome in women inthe HCHSSOL was minor For examplethe use of the 90 cm threshold (insteadof 88 cm) as recommended by Aschneret al (25) reduced the prevalence of themetabolic syndrome in the women ofthe HCHSSOL samples by only 1ndash2
Various names and definitions havebeen applied to themetabolic syndromesince its original description by Reaven(26) as a cluster of metabolic risk factorsrelated to insulin resistance There isconsensus at this time that insulin resis-tance underlies the clustering of meta-bolic syndrome abnormalities and that
Figure 2mdashPrevalence () of individual cardiometabolic abnormalities in men (A) and women (B) with the metabolic syndrome in the HCHSSOLcohort by HispanicLatino background Error bars represent the SE
2396 Prevalence of Metabolic Syndrome in HispanicsLatinos Diabetes Care Volume 37 August 2014
these are associated with an increasedrisk of type 2 diabetes and cardiovascu-lar sequelae (7) Such associations arewell-established for the individual com-ponents of this syndrome regardless ofwhether they occur in isolation in com-bination or as a qualitatively definedsyndrome based on any three cardio-metabolic abnormalities Although themetabolic syndrome is embedded inclinical management guidelines thereis no consensus about the value of themetabolic syndrome as a tool to screenfor future risk of type 2 diabetes or car-diovascular diseases Whether thecardiometabolic risk factors that con-stitute the metabolic syndrome occuralone or in clusters evidence indicatesthat all such risk factors should be ad-dressed individually and managedeffectively (27) To our knowledge noevidence has been put forward to datefor nonadditivity of these metabolicfactors on the risk of type 2 diabetesincident cardiovascular disease ormortality (ie that the risk associatedwith the metabolic syndrome exceedsthe risk conferred by the sum of theindividual cardiometabolic risk factorsthat contributes to the syndrome)(27ndash29)To aid in the interpretation of waist
circumference Lemieux et al (30) pro-posed the concurrent measurement offasting triglycerides as an inexpensivemeans to screen for the atherogenicmetabolic dysregulation triad charac-terized by hyperinsulinemia elevatedapolipoprotein B level and small denseLDL-C In the HCHSSOL data fastingtriglyceride levels HDL-C levels systolicblood pressure and fasting glucoselevels each were associated with waistcircumference in a monotonically in-creasing (graded) linear fashion with-out indications of an inflection pointor a threshold for waist circumference(data not shown)As a qualitative approach to the
characterization of cardiometabolic ab-normalities associatedwith insulin resis-tance the metabolic syndrome hasbeen endorsed by major professionaland scientific organizations (7) Al-though the Endocrine Society endorsedthe use of the metabolic syndrome inclinical practice guidelines as a toolfor primary prevention of type 2 diabe-tes and cardiovascular disease its rel-evance still is subject to disagreement
(31) The lack of management or ther-apies specific to this syndromedasopposed to its individual componentabnormalitiesdmakes its use in clini-cal settings counterintuitive and theneed for sex- race- and ethnic group-specific thresholds for abdominal adi-posity for a ldquouniversalrdquo definition ofthe metabolic syndrome makes thisconstruct susceptible to misclassifica-tion and remains a source of contro-versy (25)
The metabolic syndrome traits areknown to have high heritability (30ndash70) and candidate gene approacheslinkage studies and genome-wide asso-ciation studies (32) have identified sus-ceptibility regions and loci for individualmetabolic syndrome components Theheritability of the metabolic syndromeis reportedly 30 although little ofthis heritability has been accounted for(33) Evidence for a common genetic un-derpinning of the broad spectrum of themetabolic syndrome has not been forth-coming despite reports from genome-wide association studies of geneticvariants associated with more than one ofthe metabolic abnormalities included inthe metabolic syndrome (34) Althoughwell-conducted studies failed to identifysignificant genetic susceptibility to mul-tiple metabolic syndrome components(35) the modulation of metabolic syn-drome expression by gene 3 environ-ment interactiondsuch as gene 3energy expenditure interaction (36)dwarrants further study
The clustering of metabolic impair-ments and the observed temporaltrends in the prevalence of the meta-bolic syndrome are thought to resultfrom excess food consumption andorreduced levels of physical activity Ex-cess nutrient intake leads to adiposityand activation of stress signaling whichin turn results in chronic activation ofproinflammatory kinase pathways thatdesensitize the metabolic response toinsulin (37) Development of the meta-bolic syndrome in humans is alsothought to be promoted by high levelsof saturated fats supported by animalmodels where high-fat diets inducedmetabolic disease (38) Recent workhas highlighted the role of intestinal mi-crobiota in promoting the cardiometa-bolic abnormalities associated with themetabolic syndrome such as adiposityby increasing the capacity of the host to
extract energy from ingested food (39)or through interaction with the innateimmune system in modulating inflam-matory signaling (40) Murine modelssuggest that the loss of Toll-like receptor5 function in the intestinal mucosachanges gut microbiota that inducelow-grade inflammatory signalingwhich may desensitize insulin receptorsignaling leading to excess food con-sumption and the associated cardiometa-bolic abnormalities of the metabolicsyndrome (40) The excess caloric con-sumption thought to drive the currentepidemic in metabolic syndrome maytherefore be influenced in part by host-microbiota interactions
In conclusion the prevalence of themetabolic syndrome and that of thecardiometabolic abnormalities that areconsidered to be components of themetabolic syndrome is high in His-panicLatinos and varies by sex andacross HispanicLatino backgroundsAbdominal adiposity predominates inHispanicLatino women in men thecharacterization by HispanicLatinobackgrounds shows heterogeneity inthe profiles of the component cardio-metabolic abnormalities The preven-tion of metabolic abnormalities andtheir clinical management may benefitfrom awareness of the diversity in car-diometabolic dysregulation by sex andHispanicLatino background This is re-inforced by the lack of prevention poli-cies or clinical management guidelinesthat are specific to the metabolic syn-drome per se as opposed to its compo-nent factors Efforts to control thepopulation burden of cardio-metabolicrisk among HispanicsLatinos will bene-fit from the observed differences by sexand HispanicLatino backgrounds
Acknowledgments The authors thank theHispanic Community Health StudyStudy ofLatinos (HCHSSOL) participants who gener-ously contributed their time and provided thestudy data The authors also thank the HCHSSOL staff members for their dedication andexpertise A complete list of staff and inves-tigators was published in the Annals of Epide-miology 201020642ndash649 and is also availableon the study website (httpwwwcsccunceduhchs)Funding The Hispanic Community HealthStudyStudy of Latinos (HCHSSOL) was carriedout as a collaborative study supported bycontracts from the National Heart Lung andBlood Institute (NHLBI) to the University ofNorth Carolina (N01-HC65233) the University
carediabetesjournalsorg Heiss and Associates 2397
of Miami (N01-HC65234) Albert Einstein Col-lege of Medicine (N01-HC65235) NorthwesternUniversity (N01-HC65236) and San Diego StateUniversity (N01-HC65237) The following insti-tutes centers or offices contribute to theHCHSSOL through a transfer of funds to theNHLBI National Center on Minority Health andHealth Disparities the National Institute onDeafness and Other Communication Disordersthe National Institute of Dental and CraniofacialResearch the National Institute of Diabetes andDigestive and Kidney Diseases the NationalInstitute of Neurological Disorders and Strokeand the Office of Dietary Supplements
The funding agency had a role in the design andconduct of the study in the collection analysisand interpretation of the data and in the reviewand approval of the manuscriptDuality of Interest No potential conflicts ofinterest relevant to this article were reportedAuthors Contributions GH researched theliterature interpreted the data and organizedand wrote the manuscript MLS NS MMLCC MC RK AG LG LL and LA-Scontributed to the interpretation of the dataand to the writing of the manuscript and wereinvolved in editing during manuscript prepara-tion YT conducted the statistical analysesprovided comments and had oversight of theverification of results GH is the guarantorof this work and as such had full access to allthe data in the study and takes responsibility forthe integrity of the data and the accuracy of thedata analysisPrior Presentation A set of preliminary datafrom this study was presented at the Epidemi-ology and PreventionNutrition Physical Activ-ity and Metabolism 2013 Scientific Sessions ofthe American Heart AssociationAmericanStroke Association New Orleans LA 19ndash22March 2013
References1 Hossain P Kawar B El Nahas M Obesity anddiabetes in the developing worldda growingchallenge N Engl J Med 2007356213ndash2152 BeydounMA Wang Y Gender-ethnic dispar-ity in BMI and waist circumference distributionshifts in US adults Obesity (Silver Spring) 200917169ndash1763 Olshansky SJ Passaro DJ Hershow RC et alA potential decline in life expectancy in theUnited States in the 21st century N Engl JMed 20053521138ndash11454 Ford ES Li C Sattar N Metabolic syndromeand incident diabetes current state of the evi-dence Diabetes Care 2008311898ndash19045 Ballantyne CM Hoogeveen RC McNeill AMet al Metabolic syndrome risk for cardiovascu-lar disease and diabetes in the ARIC study Int JObes (Lond) 200832(Suppl 2)S21ndashS246 Lakka HM Laaksonen DE Lakka TA et al Themetabolic syndrome and total and cardiovascu-lar disease mortality in middle-aged men JAMA20022882709ndash27167 Alberti KG Eckel RH Grundy SM et al In-ternational Diabetes Federation Task Force onEpidemiology and Prevention National HeartLung and Blood Institute American HeartAssociation World Heart Federation Interna-tional Atherosclerosis Society International As-sociation for the Study of Obesity Harmonizing
the metabolic syndrome a joint interim state-ment of the International Diabetes Federationtask force on epidemiology and prevention Na-tional Heart Lung and Blood Institute Ameri-can Heart Association World Heart FederationInternational Atherosclerosis Society and In-ternational Association for the Study of Obe-sity Circulation 20091201640ndash16458 Ford ES Giles WH Dietz WH Prevalence ofthe metabolic syndrome among US adultsfindings from the third National Health and Nu-trition Examination Survey JAMA 2002287356ndash3599 Lavange LM Kalsbeek WD Sorlie PD et alSample design and cohort selection in the His-panic Community Health StudyStudy of Lati-nos Ann Epidemiol 201020642ndash64910 Ford ES Li C Zhao G Prevalence and corre-lates of metabolic syndrome based on a harmo-nious definition among adults in the USJ Diabetes 20102180ndash19311 Daviglus ML Talavera GA Aviles-Santa MLet al Prevalence of major cardiovascular riskfactors and cardiovascular diseases among His-panicLatino individuals of diverse backgroundsin the United States JAMA 20123081775ndash178412 Davidson JA Kannel WB Lopez-Candales Aet al Avoiding the looming LatinoHispanic car-diovascular health crisis a call to action EthnDis 200717568ndash57313 Ervin RB Prevalence of metabolic syn-drome among adults 20 years of age and overby sex age race and ethnicity and body massindex United States 2003-2006 Natl HealthStat Rep 20091ndash714 Derby CA Wildman RP McGinn AP et alCardiovascular risk factor variation within a His-panic cohort SWAN the Study of WomenrsquosHealth Across the Nation Ethn Dis 201020396ndash40215 Allison MA Budoff MJ Wong NDBlumenthal RS Schreiner PJ Criqui MH Prev-alence of and risk factors for subclinical car-diovascular disease in selected US Hispanicethnic groups the Multi-Ethnic Study of Ath-erosclerosis Am J Epidemiol 2008167962ndash96916 Schargrodsky H Hernandez-Hernandez RChampagne BM et al CARMELA Study Investi-gators CARMELA assessment of cardiovascularrisk in seven Latin American cities Am J Med200812158ndash6517 Golden SH Brown A Cauley JA et al Healthdisparities in endocrine disorders biologicalclinical and nonclinical factorsdan EndocrineSociety scientific statement J Clin EndocrinolMetab 201297E1579ndashE163918 Katzmarzyk PT Bray GA Greenway FL et alEthnic-specific BMI and waist circumferencethresholds Obesity (Silver Spring) 2011191272ndash127819 Palaniappan LPWong EC Shin JJ FortmannSP Lauderdale DS Asian Americans havegreater prevalence of metabolic syndrome de-spite lower body mass index Int J Obes (Lond)201135393ndash40020 Sumner AE Sen S Ricks M Frempong BASebring NG Kushner H Determining the waistcircumference in African Americans which bestpredicts insulin resistance Obesity (SilverSpring) 200816841ndash846
21 Barbosa PJ Lessa I de Almeida Filho NMagalhatildees LB Araujo J Criteria for centralobesity in a Brazilian population impact onmet-abolic syndrome Arq Bras Cardiol 200687407ndash41422 Medina-Lezama J Pastorius CA Zea-Diaz Het al PREVENCION Investigators Optimal defini-tions for abdominal obesity and the metabolicsyndrome in Andean Hispanics the PREVENCIONstudy Diabetes Care 2010331385ndash138823 Perez M Casas JP Cubillos-Garzon LA et alUsing waist circumference as a screening tool toidentify Colombian subjects at cardiovascularrisk Eur J Cardiovasc Prev Rehabil 200310328ndash33524 Sanchez-Castillo CP Velazquez-Monroy OBerber A Lara-Esqueda A Tapia-Conyer RJames WP Encuesta Nacional de Salud (ENSA)2000 Working Group Anthropometric cutoffpoints for predicting chronic diseases in theMexican National Health Survey 2000 ObesRes 200311442ndash45125 Aschner P Buendıa R Brajkovich I et alDetermination of the cutoff point for waist cir-cumference that establishes the presence of ab-dominal obesity in Latin American men andwomen Diabetes Res Clin Pract 201193243ndash24726 Reaven GM Banting lecture 1988 Role ofinsulin resistance in human disease Diabetes1988371595ndash160727 Kahn R Buse J Ferrannini E SternM Amer-ican Diabetes Association European Associa-tion for the Study of Diabetes The metabolicsyndrome time for a critical appraisal jointstatement from the American Diabetes Associ-ation and the European Association for theStudy of Diabetes Diabetes Care 2005282289ndash230428 Grundy SM Metabolic syndrome pan-demic Arterioscler Thromb Vasc Biol 200828629ndash63629 Bruno G Fornengo P Segre O et al What isthe clinical usefulness of the metabolic syn-drome The Casale Monferrato study J Hyper-tens 2009272403ndash240830 Lemieux I Pascot A Couillard C et al Hy-pertriglyceridemic waist a marker of the ath-erogenic metabolic triad (hyperinsulinemiahyperapolipoprotein B small dense LDL) inmen Circulation 2000102179ndash18431 Rosenzweig JL Ferrannini E Grundy SMet al Endocrine Society Primary preventionof cardiovascular disease and type 2 diabetesin patients at metabolic risk an endocrine soci-ety clinical practice guideline J Clin EndocrinolMetab 2008933671ndash368932 Aguilera CM Olza J Gil A Genetic suscep-tibility to obesity and metabolic syndrome inchildhood Nutr Hosp 201328(Suppl 5)44ndash5533 Benyamin B Soslashrensen TI Schousboe KFenger M Visscher PM Kyvik KO Are therecommon genetic and environmental factors be-hind the endophenotypes associated with themetabolic syndrome Diabetologia 2007501880ndash188834 Dastani Z Hivert MF Timpson N et alNovel loci for adiponectin levels and their influ-ence on type 2 diabetes and metabolic traitsa multi-ethnic meta-analysis of 45891 individu-als PLoS Genet 20128e1002607
2398 Prevalence of Metabolic Syndrome in HispanicsLatinos Diabetes Care Volume 37 August 2014
35 Kristiansson K Perola M Tikkanen E et alGenome-wide screen for metabolic syndromesusceptibility loci reveals strong lipid genecontribution but no evidence for common ge-netic basis for clustering of metabolic syn-drome traits Circ Cardiovasc Genet 20125242ndash24936 Santos DM Katzmarzyk PT Diego VP et alGenotype by energy expenditure interaction
with metabolic syndrome traits the Portuguesehealthy family study PLoS One 20138e8041737 Hotamisligil GS Erbay E Nutrient sensingand inflammation in metabolic diseases NatRev Immunol 20088923ndash93438 Cani PDBibiloni R KnaufC et al Changes in gutmicrobiota control metabolic endotoxemia-inducedinflammation in high-fat diet-induced obesity anddiabetes in mice Diabetes 2008571470ndash1481
39 Turnbaugh PJ Ley RE Mahowald MAMagrini V Mardis ER Gordon JI An obesity-associated gut microbiome with increased ca-pacity for energy harvest Nature 20064441027ndash103140 Vijay-Kumar M Aitken JD Carvalho FAet al Metabolic syndrome and altered gut mi-crobiota in mice lacking Toll-like receptor 5 Sci-ence 2010328228ndash231
carediabetesjournalsorg Heiss and Associates 2399
RESULTS
Of the 39384 sampled individuals whomet eligibility criteria and were se-lected 417 enrolled in the study Af-ter the exclusion of individuals withmissingunderreported Hispanic back-ground (n = 81) or missing covariates(n = 48) 9789 women and 6530 menwere available for these analyses Asshown in Table 1 the mean baselineage was 411 years and was comparablefor all HispanicLatino groups Individu-als of Mexican origin represented closeto 40 of all sampled individualsfollowed by those of Puerto Rican(17) Cuban (14) Central American(11) Dominican (9) and SouthAmerican (7) origin Consistent withnational surveys (10) 77 of theHCHSSOL participants were over-weight (BMI 25ndash299 kgm2) or obese(BMI $30 kgm2)Approximately 77 of the partici-
pants were not born in the US Al-though 57 of the participants hadlived in the US 15 years 75indicated a preference for conductingthe interviews in Spanish About 32of the participants had less than a high
school education 28 had completedhigh school and 38 had more than ahigh school education Educationalachievement did not differ by Hispanicbackground
The age-standardized prevalence ofthe metabolic syndrome was 337(95 CI 322ndash352) in men and 360(95 CI 346ndash374) in women (Table2) The prevalence of the metabolic syn-drome increased steadily with ageoverall and in both men and womenalthough a greater increase with agewas seen in women (P value for interac-tion 0004) Variability in the prevalenceof the metabolic syndrome was seen byHispanicLatino background and by sex(Table 2) The overall prevalence of themetabolic syndrome was highest amongPuerto Ricans (37 not statistically sig-nificantly different from other groupsamong the men) and significantly (P 005) lower among South Americans(27) compared with other HispanicLatino backgroundsoverall and inwomenThe prevalence of the metabolic syn-drome was significantly (P 0005)higher in Puerto Rican women comparedwith Puerto Rican men
Figure 1 displays the prevalence ofthe number of individual cardiometa-bolic abnormalities of the metabolicsyndrome by sex and HispanicLatinobackground Overall South Americansand Dominicans had the lowest preva-lence of individual abnormalities (andthus of the metabolic syndrome)Puerto Rican women had a higher bur-den of metabolic abnormalities com-pared with Puerto Rican men and withwomen of other HispanicLatino back-ground groups (Fig 1) South Americanmen had the lowest prevalence of met-abolic syndrome abnormalities Amongwomen the prevalence of zero onetwo three four and five cardiometa-bolic abnormalities was 135 233273 199 113 and 46 respec-tively The corresponding prevalencesamong men were 207 229 229196 100 and 38 respectively
A characteristic common to bothsexes is the strong association betweenthe number of cardiometabolic abnor-malities and age The prevalence of(all) five cardiometabolic abnormalitieswas 02 in women 18ndash29 years of age10 in women 60ndash69 years of age and14 in women 70ndash74 years of age Con-versely the prevalence of zero cardio-metabolic abnormalities was 27 inwomen 18ndash29 years of age 2 inwomen 60ndash69 years of age and 05in women 70ndash74 years of age This pat-tern was comparable in men in that theprevalence of the five cardiometabolicabnormalities was 08 in men 18ndash29years of age 8 in men 60ndash69 years ofage and 10 inmen 70ndash74 years of ageHowever unlike women the prevalenceof zero cardiometabolic abnormalitieswas 43 in men 18ndash29 years of age6 in men 60ndash69 years of age and 8in men 70ndash74 years of age
The profile of the cardiometabolic ab-normalities among HispanicLatinos dif-fered by sex The most prevalentcomponent of the metabolic syndromein women was abdominal obesity irre-spective of age group (SupplementaryTable 1) Among women the prevalenceof low HDL-C level was higher in those18ndash44 years of age whereas the preva-lences of elevated blood pressure andhyperglycemia were higher in those75ndash74 years of age Prevalences werehigher for hypertriglyceridemia andlow HDL-C level in men 18ndash44 years ofage whereas prevalences were higher
Table 1mdashCharacteristics of the 16319 HCHSSOL study participants included inthis report (HCHSSOL baseline examination 2008ndash2011)
Characteristics Values
Age years (mean) (SE) 411 (025)
Women () 522 6 06
HispanicLatino background N ()Dominican 1457 (89)Central American 1725 (105)Cuban 2343 (143)Mexican 6451 (393)Puerto Rican 2702 (165)South American 1063 (65)Mixedother 497 (30)
BMI ()daggerUnderweightnormal (25 kgm2) 231 6 05Overweight (25ndash299 kgm2) 371 6 06Obese ($30 kgm2) 396 6 07Missing information 02 6 005
Years in the US 15 years () 570 6 11
Not born in the 50 US states () 773 6 08
Preference for Spanish () 749 6 09
Education ()High school 319 6 07High school 279 6 06High school 384 6 08Missing information 18 6 01
Data are N () or 6 SE unless otherwise indicated Unweighted proportions all other valuesdisplayed in this report are weighted for survey design and nonresponse daggerA total of 248 men(37) and 732 women (74) had BMI values 40 kgm2 A total of 130 individuals had BMIvalues 185 kgm2 (1)
carediabetesjournalsorg Heiss and Associates 2393
for e levated blood pressure andhyperglycemia in men 45ndash64 and75ndash74 years of age (SupplementaryTable 2) The degree to which the me-dian value of an individual risk factorwas elevated relative to the thresholdwas greater with increasing age andwith the number of risk factors in menand in women (Supplementary Tables 1and 2)Among participants with the meta-
bolic syndrome 73 of the men and96 of the women had abdominal obe-sity (exceeding waist circumferencethresholds of 102 and 88 cm respec-tively) 73 of men and 59 of womenhad hypertriglyceridemia 67 of menand 75 of women had low HDL-C lev-els 66 of men and 64 of women hadelevated blood pressure or were receiv-ing antihypertensive treatment and73 of men and 62 of women had hy-perglycemia or were receiving hypogly-cemic agents Low HDL-C values wereremarkably common in women 18ndash44years of age with the metabolic syn-drome while both elevated triglyceridelevels and low HDL-C levels were higheramong the men with metabolic syn-drome who were 65 years of ageSome variability in the prevalence of in-dividual cardiometabolic abnormalitiesacross HispanicLatino backgroundswas observed (Fig 2) Among menwith themetabolic syndrome Dominicanshad the lowest prevalence of low HDL-C
compared with men of other HispanicLatino backgrounds except PuertoRicans Among women with the meta-bolic syndrome the prevalence ofabdominal adiposity was high regard-less of HispanicLatino backgroundDominican women had the lowestprevalence of hypertriglyceridemiacompared with other HispanicLatinobackgrounds Mexican women had thehighest prevalence of hypertriglyceride-mia compared with women of otherHispanicLatino backgrounds exceptfor South Americans and had the low-est prevalence of elevated blood pres-sure compared with women of otherHispanicLatino backgrounds
CONCLUSIONS
HispanicsLatinos who are the largestUS minority group experience a highburden of cardiovascular risk factors(11) Obesity the metabolic syndromeand diabetes have been found tobe prevalent in LatinosHispanics atalarming rates but limitations in theavailable data combined with publichealth concerns led to recommen-dations for additional research inHispanicsLatinos to understand therisk profile of this population (12) Weadd to this body of information bydescribing the prevalence of metabolicsyndrome in its harmonized definition(7) among US HispanicLatino adultsof diverse backgrounds
The prevalence of the metabolic syn-drome in the population sampled by theHCHSSOL was 34 in men and 36 inwomen which is comparable to reportsbased on national probability samplesindicating a higher frequency of occur-rence in US Hispanics than in whites(1013) Among HCHSSOL participants21 of men and 14 of women had nocardiometabolic abnormalities 34 ofmen and 36 of women had three ormore cardiometabolic abnormalitiesand 38 of men and 46 of womenhad five or more abnormalities
The remarkable features in these dataare the high proportion of women whomeet the metabolic syndrome criterionof three or more factors in each agestratum by virtue of exceeding thethreshold value for abdominal girththe high median values of waist circum-ference observed and the progressivelylarger increments in median waist val-ues across increasing numbers of riskfactors present This suggests that ab-dominal adiposity is the salient contrib-utor to the metabolic syndrome amongthe women in the HCHSSOL to agreater degree than for example ele-vated blood pressure or the impair-ments in lipid or glucose metabolismthat are often associated with the for-mer A limitation of these data is the lowresponse at the level of the sampledhouseholds which was 335 All esti-mates are adjusted for nonresponse (9)
As is the case for much of the existingresearch on the health status of His-panicLatino groups in the US mostprevious reports on the metabolic syn-drome among Hispanics are based onMexican Americans or a pooled hetero-geneous group of HispanicsLatinos Al-though limited by small numbers a priorreport (14) identified heterogeneity inthe frequency of the metabolic syn-drome and its components in womenby HispanicLatino background As alsoobserved among the women in theHCHSSOL the prevalence of metabolicsyndrome in the New Jersey site ofthe Study of Womenrsquos Health Acrossthe Nation was greatest in Puerto Ricanwomen (48) and was lowest in Domini-can women at this Study of WomenrsquosHealth Across the Nation site (13) al-though the SEs for these estimates wererather large Similar patterns were ob-served in the Multi-Ethnic Study of Ath-erosclerosis in that Dominicanmen and
Table 2mdashAge-standardized prevalence of the metabolic syndrome by HispanicLatino background and sex 2008ndash2011
CharacteristicsAll participants(N = 16319)
Men(N = 6530)
Women(N = 9789)
Overall 350 (340ndash361) 337 (322ndash352) 360 (346ndash374)
HispanicLatino backgroundDominican (n = 1457) 315 (290ndash340) 306 (263ndash352) 322 (289ndash358)Central American (n = 1725) 358 (330ndash387) 326 (285ndash369) 377 (347ndash408)Cuban (n = 2343) 348 (326ndash370) 347 (319ndash376) 349 (320ndash379)Mexican (n = 6451) 350 (332ndash369) 337 (313ndash362) 360 (335ndash386)Puerto Rican (n = 2702) 371 (344ndash399) 326 (287ndash368) 409 (374ndash446)South American (n = 1063) 273 (242ndash307)dagger 270 (223ndash324) 268 (231ndash309)Dagger
Age-groups (years)18ndash29 (n = 2644) 127 (111ndash144) 129 (108ndash153) 124 (103ndash149)30ndash39 (n = 2375) 247 (225ndash271) 271 (236ndash309) 224 (195ndash257)40ndash49 (n = 4194) 367 (345ndash390) 361 (329ndash394) 373 (345ndash401)50ndash59 (n = 4323) 486 (459ndash514) 448 (413ndash484) 516 (482ndash551)60ndash69 (n = 2283) 568 (538ndash598) 523 (477ndash569) 606 (563ndash647)70ndash74 (n = 500) 666 (603ndash723) 580 (496ndash659) 720 (635ndash793)
Data are (95 CI) Values were weighted for survey design and nonresponse and wereage-standardized to the population described by the 2010 US Census Statistically significantdifferences (P 005) were seen between sexes daggerStatistically significant differences (P 005)were seen among HispanicLatino backgrounds overall DaggerStatistically significant differences(P 005) were seen among women
2394 Prevalence of Metabolic Syndrome in HispanicsLatinos Diabetes Care Volume 37 August 2014
women had a lower prevalence ofthe metabolic syndrome than PuertoRicans (15)The Cardiovascular Risk Factor Mul-
tiple Evaluation in Latin America(CARMELA) study (16) compared theprevalence of the metabolic syndromein residents 25ndash64 years of age (averageage 456 11 years) in seven Latin Amer-ican cities between 2003 and 2005(1600 examinees per city) The prev-alence of the metabolic syndrome de-fined according to the Adult TreatmentPanel III criteria age- and sex-adjustedto the sample from each city rangedfrom 14 in Quito Ecuador to 27 inMexico City Mexico For comparisonuse of the Adult Treatment Panel IIIcriteria in the 2003ndash2006 NHANESshowed a prevalence of 33 amongMexican American men and 41 amongMexican American women (13) Among
the sites surveyed by the CARMELAstudy Mexico City had the highest prev-alence of obesity (31) the metabolicsyndrome (27) and diabetes (9)The prevalence of the metabolic syn-drome observed in the HCHSSOL (34in men and 36 in women) is some-what higher than that estimated by theCARMELA study forMexico City and wasnotoriously higher than those observedin Barquisimeto Venezuela Bogota Co-lombia Buenos Aires Argentina LimaPeru Quito Ecuador and SantiagoChile
Other noteworthy findings from theHCHSSOL population are that 96 ofwomen and 73 of men with the meta-bolic syndrome had abdominal obesityusing the conventional 10288 cmthreshold The International DiabetesFederation conceived of the metabolicsyndrome based onwaist circumference
thresholds that differ for race and ethnicgroups and are considerably lower thanthose originally used in the NationalCholesterol Education Program criteriaIn its 2012 scientific statement on healthdisparities in endocrine disorders (17)the Endocrine Society called for thestudy and adoption of ethnic-specificcut points for central obesity to avoidmisclassification and for appropriaterisk management A number of reports(18ndash20) have raised concerns about thethreshold values for waist circumferenceused by the current definitions of abdom-inal obesity particularly as applied toAsian African American Polynesianand HispanicLatino populations Theprevalence of the metabolic syndromeaccording to different waist circumfer-ence thresholds has been publishedbased on NHANES 2003ndash2006 data (10)When less restrictive definitions of
Figure 1mdashPrevalence () of the number of individual cardiometabolic abnormalities in men (A) and women (B) in the HCHSSOL cohort by HispanicLatino background Error bars represent the SE
carediabetesjournalsorg Heiss and Associates 2395
central obesity were used prevalence es-timates increased as expected whereasassociations with cardiometabolic corre-lates were not visibly affectedRecognizing that the risk associated
with a given waist measurement differsacross populations waist circumferencethresholds recommended for ethnicCentral and South American popula-tions in the 2009 consensus Joint Scien-tific Statement (11) are$90 cm for menand $80 cm for women Instead thedata presented in this report are basedon the waist circumference thresholdsfamiliar to clinical practitioners in theUS ($102 cm in men and $88 cm inwomen) and are used as a commonmetric in reports from the NHANES(15) For comparability with studiesbased in other countries we replicatedour analyses using the$90 cm$80 cm
thresholds for men and women respec-tively recommended by the consensusJoint Scientific Statement (11) for ethnicCentral and South American popula-tions (these data are presented in Sup-plementary Table 3)
There have been several attempts toestablish waist circumference cutoff val-ues for abdominal obesity suitable towomen in Latin America drawing onvarious criteria such as detection of di-abetes (21) abnormal carotid artery in-tima media thickness (22) blood lipidprofile and other risk factors (23) andhypertension (24) Based on an area ofvisceral adipose tissue $100 cm2 mea-sured by computed tomography scan atthe 5th lumbar vertebra Aschner et al(25) recommended 94 cm for men and90 cm for women as the threshold ofabdominal obesity We examined the
impact of waist circumference thresholdvalues recommended by various au-thors for HispanicLatino populationson the prevalence of the metabolic syn-drome in the HCHSSOL populationsOverall their impact on the prevalenceof the metabolic syndrome in women inthe HCHSSOL was minor For examplethe use of the 90 cm threshold (insteadof 88 cm) as recommended by Aschneret al (25) reduced the prevalence of themetabolic syndrome in the women ofthe HCHSSOL samples by only 1ndash2
Various names and definitions havebeen applied to themetabolic syndromesince its original description by Reaven(26) as a cluster of metabolic risk factorsrelated to insulin resistance There isconsensus at this time that insulin resis-tance underlies the clustering of meta-bolic syndrome abnormalities and that
Figure 2mdashPrevalence () of individual cardiometabolic abnormalities in men (A) and women (B) with the metabolic syndrome in the HCHSSOLcohort by HispanicLatino background Error bars represent the SE
2396 Prevalence of Metabolic Syndrome in HispanicsLatinos Diabetes Care Volume 37 August 2014
these are associated with an increasedrisk of type 2 diabetes and cardiovascu-lar sequelae (7) Such associations arewell-established for the individual com-ponents of this syndrome regardless ofwhether they occur in isolation in com-bination or as a qualitatively definedsyndrome based on any three cardio-metabolic abnormalities Although themetabolic syndrome is embedded inclinical management guidelines thereis no consensus about the value of themetabolic syndrome as a tool to screenfor future risk of type 2 diabetes or car-diovascular diseases Whether thecardiometabolic risk factors that con-stitute the metabolic syndrome occuralone or in clusters evidence indicatesthat all such risk factors should be ad-dressed individually and managedeffectively (27) To our knowledge noevidence has been put forward to datefor nonadditivity of these metabolicfactors on the risk of type 2 diabetesincident cardiovascular disease ormortality (ie that the risk associatedwith the metabolic syndrome exceedsthe risk conferred by the sum of theindividual cardiometabolic risk factorsthat contributes to the syndrome)(27ndash29)To aid in the interpretation of waist
circumference Lemieux et al (30) pro-posed the concurrent measurement offasting triglycerides as an inexpensivemeans to screen for the atherogenicmetabolic dysregulation triad charac-terized by hyperinsulinemia elevatedapolipoprotein B level and small denseLDL-C In the HCHSSOL data fastingtriglyceride levels HDL-C levels systolicblood pressure and fasting glucoselevels each were associated with waistcircumference in a monotonically in-creasing (graded) linear fashion with-out indications of an inflection pointor a threshold for waist circumference(data not shown)As a qualitative approach to the
characterization of cardiometabolic ab-normalities associatedwith insulin resis-tance the metabolic syndrome hasbeen endorsed by major professionaland scientific organizations (7) Al-though the Endocrine Society endorsedthe use of the metabolic syndrome inclinical practice guidelines as a toolfor primary prevention of type 2 diabe-tes and cardiovascular disease its rel-evance still is subject to disagreement
(31) The lack of management or ther-apies specific to this syndromedasopposed to its individual componentabnormalitiesdmakes its use in clini-cal settings counterintuitive and theneed for sex- race- and ethnic group-specific thresholds for abdominal adi-posity for a ldquouniversalrdquo definition ofthe metabolic syndrome makes thisconstruct susceptible to misclassifica-tion and remains a source of contro-versy (25)
The metabolic syndrome traits areknown to have high heritability (30ndash70) and candidate gene approacheslinkage studies and genome-wide asso-ciation studies (32) have identified sus-ceptibility regions and loci for individualmetabolic syndrome components Theheritability of the metabolic syndromeis reportedly 30 although little ofthis heritability has been accounted for(33) Evidence for a common genetic un-derpinning of the broad spectrum of themetabolic syndrome has not been forth-coming despite reports from genome-wide association studies of geneticvariants associated with more than one ofthe metabolic abnormalities included inthe metabolic syndrome (34) Althoughwell-conducted studies failed to identifysignificant genetic susceptibility to mul-tiple metabolic syndrome components(35) the modulation of metabolic syn-drome expression by gene 3 environ-ment interactiondsuch as gene 3energy expenditure interaction (36)dwarrants further study
The clustering of metabolic impair-ments and the observed temporaltrends in the prevalence of the meta-bolic syndrome are thought to resultfrom excess food consumption andorreduced levels of physical activity Ex-cess nutrient intake leads to adiposityand activation of stress signaling whichin turn results in chronic activation ofproinflammatory kinase pathways thatdesensitize the metabolic response toinsulin (37) Development of the meta-bolic syndrome in humans is alsothought to be promoted by high levelsof saturated fats supported by animalmodels where high-fat diets inducedmetabolic disease (38) Recent workhas highlighted the role of intestinal mi-crobiota in promoting the cardiometa-bolic abnormalities associated with themetabolic syndrome such as adiposityby increasing the capacity of the host to
extract energy from ingested food (39)or through interaction with the innateimmune system in modulating inflam-matory signaling (40) Murine modelssuggest that the loss of Toll-like receptor5 function in the intestinal mucosachanges gut microbiota that inducelow-grade inflammatory signalingwhich may desensitize insulin receptorsignaling leading to excess food con-sumption and the associated cardiometa-bolic abnormalities of the metabolicsyndrome (40) The excess caloric con-sumption thought to drive the currentepidemic in metabolic syndrome maytherefore be influenced in part by host-microbiota interactions
In conclusion the prevalence of themetabolic syndrome and that of thecardiometabolic abnormalities that areconsidered to be components of themetabolic syndrome is high in His-panicLatinos and varies by sex andacross HispanicLatino backgroundsAbdominal adiposity predominates inHispanicLatino women in men thecharacterization by HispanicLatinobackgrounds shows heterogeneity inthe profiles of the component cardio-metabolic abnormalities The preven-tion of metabolic abnormalities andtheir clinical management may benefitfrom awareness of the diversity in car-diometabolic dysregulation by sex andHispanicLatino background This is re-inforced by the lack of prevention poli-cies or clinical management guidelinesthat are specific to the metabolic syn-drome per se as opposed to its compo-nent factors Efforts to control thepopulation burden of cardio-metabolicrisk among HispanicsLatinos will bene-fit from the observed differences by sexand HispanicLatino backgrounds
Acknowledgments The authors thank theHispanic Community Health StudyStudy ofLatinos (HCHSSOL) participants who gener-ously contributed their time and provided thestudy data The authors also thank the HCHSSOL staff members for their dedication andexpertise A complete list of staff and inves-tigators was published in the Annals of Epide-miology 201020642ndash649 and is also availableon the study website (httpwwwcsccunceduhchs)Funding The Hispanic Community HealthStudyStudy of Latinos (HCHSSOL) was carriedout as a collaborative study supported bycontracts from the National Heart Lung andBlood Institute (NHLBI) to the University ofNorth Carolina (N01-HC65233) the University
carediabetesjournalsorg Heiss and Associates 2397
of Miami (N01-HC65234) Albert Einstein Col-lege of Medicine (N01-HC65235) NorthwesternUniversity (N01-HC65236) and San Diego StateUniversity (N01-HC65237) The following insti-tutes centers or offices contribute to theHCHSSOL through a transfer of funds to theNHLBI National Center on Minority Health andHealth Disparities the National Institute onDeafness and Other Communication Disordersthe National Institute of Dental and CraniofacialResearch the National Institute of Diabetes andDigestive and Kidney Diseases the NationalInstitute of Neurological Disorders and Strokeand the Office of Dietary Supplements
The funding agency had a role in the design andconduct of the study in the collection analysisand interpretation of the data and in the reviewand approval of the manuscriptDuality of Interest No potential conflicts ofinterest relevant to this article were reportedAuthors Contributions GH researched theliterature interpreted the data and organizedand wrote the manuscript MLS NS MMLCC MC RK AG LG LL and LA-Scontributed to the interpretation of the dataand to the writing of the manuscript and wereinvolved in editing during manuscript prepara-tion YT conducted the statistical analysesprovided comments and had oversight of theverification of results GH is the guarantorof this work and as such had full access to allthe data in the study and takes responsibility forthe integrity of the data and the accuracy of thedata analysisPrior Presentation A set of preliminary datafrom this study was presented at the Epidemi-ology and PreventionNutrition Physical Activ-ity and Metabolism 2013 Scientific Sessions ofthe American Heart AssociationAmericanStroke Association New Orleans LA 19ndash22March 2013
References1 Hossain P Kawar B El Nahas M Obesity anddiabetes in the developing worldda growingchallenge N Engl J Med 2007356213ndash2152 BeydounMA Wang Y Gender-ethnic dispar-ity in BMI and waist circumference distributionshifts in US adults Obesity (Silver Spring) 200917169ndash1763 Olshansky SJ Passaro DJ Hershow RC et alA potential decline in life expectancy in theUnited States in the 21st century N Engl JMed 20053521138ndash11454 Ford ES Li C Sattar N Metabolic syndromeand incident diabetes current state of the evi-dence Diabetes Care 2008311898ndash19045 Ballantyne CM Hoogeveen RC McNeill AMet al Metabolic syndrome risk for cardiovascu-lar disease and diabetes in the ARIC study Int JObes (Lond) 200832(Suppl 2)S21ndashS246 Lakka HM Laaksonen DE Lakka TA et al Themetabolic syndrome and total and cardiovascu-lar disease mortality in middle-aged men JAMA20022882709ndash27167 Alberti KG Eckel RH Grundy SM et al In-ternational Diabetes Federation Task Force onEpidemiology and Prevention National HeartLung and Blood Institute American HeartAssociation World Heart Federation Interna-tional Atherosclerosis Society International As-sociation for the Study of Obesity Harmonizing
the metabolic syndrome a joint interim state-ment of the International Diabetes Federationtask force on epidemiology and prevention Na-tional Heart Lung and Blood Institute Ameri-can Heart Association World Heart FederationInternational Atherosclerosis Society and In-ternational Association for the Study of Obe-sity Circulation 20091201640ndash16458 Ford ES Giles WH Dietz WH Prevalence ofthe metabolic syndrome among US adultsfindings from the third National Health and Nu-trition Examination Survey JAMA 2002287356ndash3599 Lavange LM Kalsbeek WD Sorlie PD et alSample design and cohort selection in the His-panic Community Health StudyStudy of Lati-nos Ann Epidemiol 201020642ndash64910 Ford ES Li C Zhao G Prevalence and corre-lates of metabolic syndrome based on a harmo-nious definition among adults in the USJ Diabetes 20102180ndash19311 Daviglus ML Talavera GA Aviles-Santa MLet al Prevalence of major cardiovascular riskfactors and cardiovascular diseases among His-panicLatino individuals of diverse backgroundsin the United States JAMA 20123081775ndash178412 Davidson JA Kannel WB Lopez-Candales Aet al Avoiding the looming LatinoHispanic car-diovascular health crisis a call to action EthnDis 200717568ndash57313 Ervin RB Prevalence of metabolic syn-drome among adults 20 years of age and overby sex age race and ethnicity and body massindex United States 2003-2006 Natl HealthStat Rep 20091ndash714 Derby CA Wildman RP McGinn AP et alCardiovascular risk factor variation within a His-panic cohort SWAN the Study of WomenrsquosHealth Across the Nation Ethn Dis 201020396ndash40215 Allison MA Budoff MJ Wong NDBlumenthal RS Schreiner PJ Criqui MH Prev-alence of and risk factors for subclinical car-diovascular disease in selected US Hispanicethnic groups the Multi-Ethnic Study of Ath-erosclerosis Am J Epidemiol 2008167962ndash96916 Schargrodsky H Hernandez-Hernandez RChampagne BM et al CARMELA Study Investi-gators CARMELA assessment of cardiovascularrisk in seven Latin American cities Am J Med200812158ndash6517 Golden SH Brown A Cauley JA et al Healthdisparities in endocrine disorders biologicalclinical and nonclinical factorsdan EndocrineSociety scientific statement J Clin EndocrinolMetab 201297E1579ndashE163918 Katzmarzyk PT Bray GA Greenway FL et alEthnic-specific BMI and waist circumferencethresholds Obesity (Silver Spring) 2011191272ndash127819 Palaniappan LPWong EC Shin JJ FortmannSP Lauderdale DS Asian Americans havegreater prevalence of metabolic syndrome de-spite lower body mass index Int J Obes (Lond)201135393ndash40020 Sumner AE Sen S Ricks M Frempong BASebring NG Kushner H Determining the waistcircumference in African Americans which bestpredicts insulin resistance Obesity (SilverSpring) 200816841ndash846
21 Barbosa PJ Lessa I de Almeida Filho NMagalhatildees LB Araujo J Criteria for centralobesity in a Brazilian population impact onmet-abolic syndrome Arq Bras Cardiol 200687407ndash41422 Medina-Lezama J Pastorius CA Zea-Diaz Het al PREVENCION Investigators Optimal defini-tions for abdominal obesity and the metabolicsyndrome in Andean Hispanics the PREVENCIONstudy Diabetes Care 2010331385ndash138823 Perez M Casas JP Cubillos-Garzon LA et alUsing waist circumference as a screening tool toidentify Colombian subjects at cardiovascularrisk Eur J Cardiovasc Prev Rehabil 200310328ndash33524 Sanchez-Castillo CP Velazquez-Monroy OBerber A Lara-Esqueda A Tapia-Conyer RJames WP Encuesta Nacional de Salud (ENSA)2000 Working Group Anthropometric cutoffpoints for predicting chronic diseases in theMexican National Health Survey 2000 ObesRes 200311442ndash45125 Aschner P Buendıa R Brajkovich I et alDetermination of the cutoff point for waist cir-cumference that establishes the presence of ab-dominal obesity in Latin American men andwomen Diabetes Res Clin Pract 201193243ndash24726 Reaven GM Banting lecture 1988 Role ofinsulin resistance in human disease Diabetes1988371595ndash160727 Kahn R Buse J Ferrannini E SternM Amer-ican Diabetes Association European Associa-tion for the Study of Diabetes The metabolicsyndrome time for a critical appraisal jointstatement from the American Diabetes Associ-ation and the European Association for theStudy of Diabetes Diabetes Care 2005282289ndash230428 Grundy SM Metabolic syndrome pan-demic Arterioscler Thromb Vasc Biol 200828629ndash63629 Bruno G Fornengo P Segre O et al What isthe clinical usefulness of the metabolic syn-drome The Casale Monferrato study J Hyper-tens 2009272403ndash240830 Lemieux I Pascot A Couillard C et al Hy-pertriglyceridemic waist a marker of the ath-erogenic metabolic triad (hyperinsulinemiahyperapolipoprotein B small dense LDL) inmen Circulation 2000102179ndash18431 Rosenzweig JL Ferrannini E Grundy SMet al Endocrine Society Primary preventionof cardiovascular disease and type 2 diabetesin patients at metabolic risk an endocrine soci-ety clinical practice guideline J Clin EndocrinolMetab 2008933671ndash368932 Aguilera CM Olza J Gil A Genetic suscep-tibility to obesity and metabolic syndrome inchildhood Nutr Hosp 201328(Suppl 5)44ndash5533 Benyamin B Soslashrensen TI Schousboe KFenger M Visscher PM Kyvik KO Are therecommon genetic and environmental factors be-hind the endophenotypes associated with themetabolic syndrome Diabetologia 2007501880ndash188834 Dastani Z Hivert MF Timpson N et alNovel loci for adiponectin levels and their influ-ence on type 2 diabetes and metabolic traitsa multi-ethnic meta-analysis of 45891 individu-als PLoS Genet 20128e1002607
2398 Prevalence of Metabolic Syndrome in HispanicsLatinos Diabetes Care Volume 37 August 2014
35 Kristiansson K Perola M Tikkanen E et alGenome-wide screen for metabolic syndromesusceptibility loci reveals strong lipid genecontribution but no evidence for common ge-netic basis for clustering of metabolic syn-drome traits Circ Cardiovasc Genet 20125242ndash24936 Santos DM Katzmarzyk PT Diego VP et alGenotype by energy expenditure interaction
with metabolic syndrome traits the Portuguesehealthy family study PLoS One 20138e8041737 Hotamisligil GS Erbay E Nutrient sensingand inflammation in metabolic diseases NatRev Immunol 20088923ndash93438 Cani PDBibiloni R KnaufC et al Changes in gutmicrobiota control metabolic endotoxemia-inducedinflammation in high-fat diet-induced obesity anddiabetes in mice Diabetes 2008571470ndash1481
39 Turnbaugh PJ Ley RE Mahowald MAMagrini V Mardis ER Gordon JI An obesity-associated gut microbiome with increased ca-pacity for energy harvest Nature 20064441027ndash103140 Vijay-Kumar M Aitken JD Carvalho FAet al Metabolic syndrome and altered gut mi-crobiota in mice lacking Toll-like receptor 5 Sci-ence 2010328228ndash231
carediabetesjournalsorg Heiss and Associates 2399
for e levated blood pressure andhyperglycemia in men 45ndash64 and75ndash74 years of age (SupplementaryTable 2) The degree to which the me-dian value of an individual risk factorwas elevated relative to the thresholdwas greater with increasing age andwith the number of risk factors in menand in women (Supplementary Tables 1and 2)Among participants with the meta-
bolic syndrome 73 of the men and96 of the women had abdominal obe-sity (exceeding waist circumferencethresholds of 102 and 88 cm respec-tively) 73 of men and 59 of womenhad hypertriglyceridemia 67 of menand 75 of women had low HDL-C lev-els 66 of men and 64 of women hadelevated blood pressure or were receiv-ing antihypertensive treatment and73 of men and 62 of women had hy-perglycemia or were receiving hypogly-cemic agents Low HDL-C values wereremarkably common in women 18ndash44years of age with the metabolic syn-drome while both elevated triglyceridelevels and low HDL-C levels were higheramong the men with metabolic syn-drome who were 65 years of ageSome variability in the prevalence of in-dividual cardiometabolic abnormalitiesacross HispanicLatino backgroundswas observed (Fig 2) Among menwith themetabolic syndrome Dominicanshad the lowest prevalence of low HDL-C
compared with men of other HispanicLatino backgrounds except PuertoRicans Among women with the meta-bolic syndrome the prevalence ofabdominal adiposity was high regard-less of HispanicLatino backgroundDominican women had the lowestprevalence of hypertriglyceridemiacompared with other HispanicLatinobackgrounds Mexican women had thehighest prevalence of hypertriglyceride-mia compared with women of otherHispanicLatino backgrounds exceptfor South Americans and had the low-est prevalence of elevated blood pres-sure compared with women of otherHispanicLatino backgrounds
CONCLUSIONS
HispanicsLatinos who are the largestUS minority group experience a highburden of cardiovascular risk factors(11) Obesity the metabolic syndromeand diabetes have been found tobe prevalent in LatinosHispanics atalarming rates but limitations in theavailable data combined with publichealth concerns led to recommen-dations for additional research inHispanicsLatinos to understand therisk profile of this population (12) Weadd to this body of information bydescribing the prevalence of metabolicsyndrome in its harmonized definition(7) among US HispanicLatino adultsof diverse backgrounds
The prevalence of the metabolic syn-drome in the population sampled by theHCHSSOL was 34 in men and 36 inwomen which is comparable to reportsbased on national probability samplesindicating a higher frequency of occur-rence in US Hispanics than in whites(1013) Among HCHSSOL participants21 of men and 14 of women had nocardiometabolic abnormalities 34 ofmen and 36 of women had three ormore cardiometabolic abnormalitiesand 38 of men and 46 of womenhad five or more abnormalities
The remarkable features in these dataare the high proportion of women whomeet the metabolic syndrome criterionof three or more factors in each agestratum by virtue of exceeding thethreshold value for abdominal girththe high median values of waist circum-ference observed and the progressivelylarger increments in median waist val-ues across increasing numbers of riskfactors present This suggests that ab-dominal adiposity is the salient contrib-utor to the metabolic syndrome amongthe women in the HCHSSOL to agreater degree than for example ele-vated blood pressure or the impair-ments in lipid or glucose metabolismthat are often associated with the for-mer A limitation of these data is the lowresponse at the level of the sampledhouseholds which was 335 All esti-mates are adjusted for nonresponse (9)
As is the case for much of the existingresearch on the health status of His-panicLatino groups in the US mostprevious reports on the metabolic syn-drome among Hispanics are based onMexican Americans or a pooled hetero-geneous group of HispanicsLatinos Al-though limited by small numbers a priorreport (14) identified heterogeneity inthe frequency of the metabolic syn-drome and its components in womenby HispanicLatino background As alsoobserved among the women in theHCHSSOL the prevalence of metabolicsyndrome in the New Jersey site ofthe Study of Womenrsquos Health Acrossthe Nation was greatest in Puerto Ricanwomen (48) and was lowest in Domini-can women at this Study of WomenrsquosHealth Across the Nation site (13) al-though the SEs for these estimates wererather large Similar patterns were ob-served in the Multi-Ethnic Study of Ath-erosclerosis in that Dominicanmen and
Table 2mdashAge-standardized prevalence of the metabolic syndrome by HispanicLatino background and sex 2008ndash2011
CharacteristicsAll participants(N = 16319)
Men(N = 6530)
Women(N = 9789)
Overall 350 (340ndash361) 337 (322ndash352) 360 (346ndash374)
HispanicLatino backgroundDominican (n = 1457) 315 (290ndash340) 306 (263ndash352) 322 (289ndash358)Central American (n = 1725) 358 (330ndash387) 326 (285ndash369) 377 (347ndash408)Cuban (n = 2343) 348 (326ndash370) 347 (319ndash376) 349 (320ndash379)Mexican (n = 6451) 350 (332ndash369) 337 (313ndash362) 360 (335ndash386)Puerto Rican (n = 2702) 371 (344ndash399) 326 (287ndash368) 409 (374ndash446)South American (n = 1063) 273 (242ndash307)dagger 270 (223ndash324) 268 (231ndash309)Dagger
Age-groups (years)18ndash29 (n = 2644) 127 (111ndash144) 129 (108ndash153) 124 (103ndash149)30ndash39 (n = 2375) 247 (225ndash271) 271 (236ndash309) 224 (195ndash257)40ndash49 (n = 4194) 367 (345ndash390) 361 (329ndash394) 373 (345ndash401)50ndash59 (n = 4323) 486 (459ndash514) 448 (413ndash484) 516 (482ndash551)60ndash69 (n = 2283) 568 (538ndash598) 523 (477ndash569) 606 (563ndash647)70ndash74 (n = 500) 666 (603ndash723) 580 (496ndash659) 720 (635ndash793)
Data are (95 CI) Values were weighted for survey design and nonresponse and wereage-standardized to the population described by the 2010 US Census Statistically significantdifferences (P 005) were seen between sexes daggerStatistically significant differences (P 005)were seen among HispanicLatino backgrounds overall DaggerStatistically significant differences(P 005) were seen among women
2394 Prevalence of Metabolic Syndrome in HispanicsLatinos Diabetes Care Volume 37 August 2014
women had a lower prevalence ofthe metabolic syndrome than PuertoRicans (15)The Cardiovascular Risk Factor Mul-
tiple Evaluation in Latin America(CARMELA) study (16) compared theprevalence of the metabolic syndromein residents 25ndash64 years of age (averageage 456 11 years) in seven Latin Amer-ican cities between 2003 and 2005(1600 examinees per city) The prev-alence of the metabolic syndrome de-fined according to the Adult TreatmentPanel III criteria age- and sex-adjustedto the sample from each city rangedfrom 14 in Quito Ecuador to 27 inMexico City Mexico For comparisonuse of the Adult Treatment Panel IIIcriteria in the 2003ndash2006 NHANESshowed a prevalence of 33 amongMexican American men and 41 amongMexican American women (13) Among
the sites surveyed by the CARMELAstudy Mexico City had the highest prev-alence of obesity (31) the metabolicsyndrome (27) and diabetes (9)The prevalence of the metabolic syn-drome observed in the HCHSSOL (34in men and 36 in women) is some-what higher than that estimated by theCARMELA study forMexico City and wasnotoriously higher than those observedin Barquisimeto Venezuela Bogota Co-lombia Buenos Aires Argentina LimaPeru Quito Ecuador and SantiagoChile
Other noteworthy findings from theHCHSSOL population are that 96 ofwomen and 73 of men with the meta-bolic syndrome had abdominal obesityusing the conventional 10288 cmthreshold The International DiabetesFederation conceived of the metabolicsyndrome based onwaist circumference
thresholds that differ for race and ethnicgroups and are considerably lower thanthose originally used in the NationalCholesterol Education Program criteriaIn its 2012 scientific statement on healthdisparities in endocrine disorders (17)the Endocrine Society called for thestudy and adoption of ethnic-specificcut points for central obesity to avoidmisclassification and for appropriaterisk management A number of reports(18ndash20) have raised concerns about thethreshold values for waist circumferenceused by the current definitions of abdom-inal obesity particularly as applied toAsian African American Polynesianand HispanicLatino populations Theprevalence of the metabolic syndromeaccording to different waist circumfer-ence thresholds has been publishedbased on NHANES 2003ndash2006 data (10)When less restrictive definitions of
Figure 1mdashPrevalence () of the number of individual cardiometabolic abnormalities in men (A) and women (B) in the HCHSSOL cohort by HispanicLatino background Error bars represent the SE
carediabetesjournalsorg Heiss and Associates 2395
central obesity were used prevalence es-timates increased as expected whereasassociations with cardiometabolic corre-lates were not visibly affectedRecognizing that the risk associated
with a given waist measurement differsacross populations waist circumferencethresholds recommended for ethnicCentral and South American popula-tions in the 2009 consensus Joint Scien-tific Statement (11) are$90 cm for menand $80 cm for women Instead thedata presented in this report are basedon the waist circumference thresholdsfamiliar to clinical practitioners in theUS ($102 cm in men and $88 cm inwomen) and are used as a commonmetric in reports from the NHANES(15) For comparability with studiesbased in other countries we replicatedour analyses using the$90 cm$80 cm
thresholds for men and women respec-tively recommended by the consensusJoint Scientific Statement (11) for ethnicCentral and South American popula-tions (these data are presented in Sup-plementary Table 3)
There have been several attempts toestablish waist circumference cutoff val-ues for abdominal obesity suitable towomen in Latin America drawing onvarious criteria such as detection of di-abetes (21) abnormal carotid artery in-tima media thickness (22) blood lipidprofile and other risk factors (23) andhypertension (24) Based on an area ofvisceral adipose tissue $100 cm2 mea-sured by computed tomography scan atthe 5th lumbar vertebra Aschner et al(25) recommended 94 cm for men and90 cm for women as the threshold ofabdominal obesity We examined the
impact of waist circumference thresholdvalues recommended by various au-thors for HispanicLatino populationson the prevalence of the metabolic syn-drome in the HCHSSOL populationsOverall their impact on the prevalenceof the metabolic syndrome in women inthe HCHSSOL was minor For examplethe use of the 90 cm threshold (insteadof 88 cm) as recommended by Aschneret al (25) reduced the prevalence of themetabolic syndrome in the women ofthe HCHSSOL samples by only 1ndash2
Various names and definitions havebeen applied to themetabolic syndromesince its original description by Reaven(26) as a cluster of metabolic risk factorsrelated to insulin resistance There isconsensus at this time that insulin resis-tance underlies the clustering of meta-bolic syndrome abnormalities and that
Figure 2mdashPrevalence () of individual cardiometabolic abnormalities in men (A) and women (B) with the metabolic syndrome in the HCHSSOLcohort by HispanicLatino background Error bars represent the SE
2396 Prevalence of Metabolic Syndrome in HispanicsLatinos Diabetes Care Volume 37 August 2014
these are associated with an increasedrisk of type 2 diabetes and cardiovascu-lar sequelae (7) Such associations arewell-established for the individual com-ponents of this syndrome regardless ofwhether they occur in isolation in com-bination or as a qualitatively definedsyndrome based on any three cardio-metabolic abnormalities Although themetabolic syndrome is embedded inclinical management guidelines thereis no consensus about the value of themetabolic syndrome as a tool to screenfor future risk of type 2 diabetes or car-diovascular diseases Whether thecardiometabolic risk factors that con-stitute the metabolic syndrome occuralone or in clusters evidence indicatesthat all such risk factors should be ad-dressed individually and managedeffectively (27) To our knowledge noevidence has been put forward to datefor nonadditivity of these metabolicfactors on the risk of type 2 diabetesincident cardiovascular disease ormortality (ie that the risk associatedwith the metabolic syndrome exceedsthe risk conferred by the sum of theindividual cardiometabolic risk factorsthat contributes to the syndrome)(27ndash29)To aid in the interpretation of waist
circumference Lemieux et al (30) pro-posed the concurrent measurement offasting triglycerides as an inexpensivemeans to screen for the atherogenicmetabolic dysregulation triad charac-terized by hyperinsulinemia elevatedapolipoprotein B level and small denseLDL-C In the HCHSSOL data fastingtriglyceride levels HDL-C levels systolicblood pressure and fasting glucoselevels each were associated with waistcircumference in a monotonically in-creasing (graded) linear fashion with-out indications of an inflection pointor a threshold for waist circumference(data not shown)As a qualitative approach to the
characterization of cardiometabolic ab-normalities associatedwith insulin resis-tance the metabolic syndrome hasbeen endorsed by major professionaland scientific organizations (7) Al-though the Endocrine Society endorsedthe use of the metabolic syndrome inclinical practice guidelines as a toolfor primary prevention of type 2 diabe-tes and cardiovascular disease its rel-evance still is subject to disagreement
(31) The lack of management or ther-apies specific to this syndromedasopposed to its individual componentabnormalitiesdmakes its use in clini-cal settings counterintuitive and theneed for sex- race- and ethnic group-specific thresholds for abdominal adi-posity for a ldquouniversalrdquo definition ofthe metabolic syndrome makes thisconstruct susceptible to misclassifica-tion and remains a source of contro-versy (25)
The metabolic syndrome traits areknown to have high heritability (30ndash70) and candidate gene approacheslinkage studies and genome-wide asso-ciation studies (32) have identified sus-ceptibility regions and loci for individualmetabolic syndrome components Theheritability of the metabolic syndromeis reportedly 30 although little ofthis heritability has been accounted for(33) Evidence for a common genetic un-derpinning of the broad spectrum of themetabolic syndrome has not been forth-coming despite reports from genome-wide association studies of geneticvariants associated with more than one ofthe metabolic abnormalities included inthe metabolic syndrome (34) Althoughwell-conducted studies failed to identifysignificant genetic susceptibility to mul-tiple metabolic syndrome components(35) the modulation of metabolic syn-drome expression by gene 3 environ-ment interactiondsuch as gene 3energy expenditure interaction (36)dwarrants further study
The clustering of metabolic impair-ments and the observed temporaltrends in the prevalence of the meta-bolic syndrome are thought to resultfrom excess food consumption andorreduced levels of physical activity Ex-cess nutrient intake leads to adiposityand activation of stress signaling whichin turn results in chronic activation ofproinflammatory kinase pathways thatdesensitize the metabolic response toinsulin (37) Development of the meta-bolic syndrome in humans is alsothought to be promoted by high levelsof saturated fats supported by animalmodels where high-fat diets inducedmetabolic disease (38) Recent workhas highlighted the role of intestinal mi-crobiota in promoting the cardiometa-bolic abnormalities associated with themetabolic syndrome such as adiposityby increasing the capacity of the host to
extract energy from ingested food (39)or through interaction with the innateimmune system in modulating inflam-matory signaling (40) Murine modelssuggest that the loss of Toll-like receptor5 function in the intestinal mucosachanges gut microbiota that inducelow-grade inflammatory signalingwhich may desensitize insulin receptorsignaling leading to excess food con-sumption and the associated cardiometa-bolic abnormalities of the metabolicsyndrome (40) The excess caloric con-sumption thought to drive the currentepidemic in metabolic syndrome maytherefore be influenced in part by host-microbiota interactions
In conclusion the prevalence of themetabolic syndrome and that of thecardiometabolic abnormalities that areconsidered to be components of themetabolic syndrome is high in His-panicLatinos and varies by sex andacross HispanicLatino backgroundsAbdominal adiposity predominates inHispanicLatino women in men thecharacterization by HispanicLatinobackgrounds shows heterogeneity inthe profiles of the component cardio-metabolic abnormalities The preven-tion of metabolic abnormalities andtheir clinical management may benefitfrom awareness of the diversity in car-diometabolic dysregulation by sex andHispanicLatino background This is re-inforced by the lack of prevention poli-cies or clinical management guidelinesthat are specific to the metabolic syn-drome per se as opposed to its compo-nent factors Efforts to control thepopulation burden of cardio-metabolicrisk among HispanicsLatinos will bene-fit from the observed differences by sexand HispanicLatino backgrounds
Acknowledgments The authors thank theHispanic Community Health StudyStudy ofLatinos (HCHSSOL) participants who gener-ously contributed their time and provided thestudy data The authors also thank the HCHSSOL staff members for their dedication andexpertise A complete list of staff and inves-tigators was published in the Annals of Epide-miology 201020642ndash649 and is also availableon the study website (httpwwwcsccunceduhchs)Funding The Hispanic Community HealthStudyStudy of Latinos (HCHSSOL) was carriedout as a collaborative study supported bycontracts from the National Heart Lung andBlood Institute (NHLBI) to the University ofNorth Carolina (N01-HC65233) the University
carediabetesjournalsorg Heiss and Associates 2397
of Miami (N01-HC65234) Albert Einstein Col-lege of Medicine (N01-HC65235) NorthwesternUniversity (N01-HC65236) and San Diego StateUniversity (N01-HC65237) The following insti-tutes centers or offices contribute to theHCHSSOL through a transfer of funds to theNHLBI National Center on Minority Health andHealth Disparities the National Institute onDeafness and Other Communication Disordersthe National Institute of Dental and CraniofacialResearch the National Institute of Diabetes andDigestive and Kidney Diseases the NationalInstitute of Neurological Disorders and Strokeand the Office of Dietary Supplements
The funding agency had a role in the design andconduct of the study in the collection analysisand interpretation of the data and in the reviewand approval of the manuscriptDuality of Interest No potential conflicts ofinterest relevant to this article were reportedAuthors Contributions GH researched theliterature interpreted the data and organizedand wrote the manuscript MLS NS MMLCC MC RK AG LG LL and LA-Scontributed to the interpretation of the dataand to the writing of the manuscript and wereinvolved in editing during manuscript prepara-tion YT conducted the statistical analysesprovided comments and had oversight of theverification of results GH is the guarantorof this work and as such had full access to allthe data in the study and takes responsibility forthe integrity of the data and the accuracy of thedata analysisPrior Presentation A set of preliminary datafrom this study was presented at the Epidemi-ology and PreventionNutrition Physical Activ-ity and Metabolism 2013 Scientific Sessions ofthe American Heart AssociationAmericanStroke Association New Orleans LA 19ndash22March 2013
References1 Hossain P Kawar B El Nahas M Obesity anddiabetes in the developing worldda growingchallenge N Engl J Med 2007356213ndash2152 BeydounMA Wang Y Gender-ethnic dispar-ity in BMI and waist circumference distributionshifts in US adults Obesity (Silver Spring) 200917169ndash1763 Olshansky SJ Passaro DJ Hershow RC et alA potential decline in life expectancy in theUnited States in the 21st century N Engl JMed 20053521138ndash11454 Ford ES Li C Sattar N Metabolic syndromeand incident diabetes current state of the evi-dence Diabetes Care 2008311898ndash19045 Ballantyne CM Hoogeveen RC McNeill AMet al Metabolic syndrome risk for cardiovascu-lar disease and diabetes in the ARIC study Int JObes (Lond) 200832(Suppl 2)S21ndashS246 Lakka HM Laaksonen DE Lakka TA et al Themetabolic syndrome and total and cardiovascu-lar disease mortality in middle-aged men JAMA20022882709ndash27167 Alberti KG Eckel RH Grundy SM et al In-ternational Diabetes Federation Task Force onEpidemiology and Prevention National HeartLung and Blood Institute American HeartAssociation World Heart Federation Interna-tional Atherosclerosis Society International As-sociation for the Study of Obesity Harmonizing
the metabolic syndrome a joint interim state-ment of the International Diabetes Federationtask force on epidemiology and prevention Na-tional Heart Lung and Blood Institute Ameri-can Heart Association World Heart FederationInternational Atherosclerosis Society and In-ternational Association for the Study of Obe-sity Circulation 20091201640ndash16458 Ford ES Giles WH Dietz WH Prevalence ofthe metabolic syndrome among US adultsfindings from the third National Health and Nu-trition Examination Survey JAMA 2002287356ndash3599 Lavange LM Kalsbeek WD Sorlie PD et alSample design and cohort selection in the His-panic Community Health StudyStudy of Lati-nos Ann Epidemiol 201020642ndash64910 Ford ES Li C Zhao G Prevalence and corre-lates of metabolic syndrome based on a harmo-nious definition among adults in the USJ Diabetes 20102180ndash19311 Daviglus ML Talavera GA Aviles-Santa MLet al Prevalence of major cardiovascular riskfactors and cardiovascular diseases among His-panicLatino individuals of diverse backgroundsin the United States JAMA 20123081775ndash178412 Davidson JA Kannel WB Lopez-Candales Aet al Avoiding the looming LatinoHispanic car-diovascular health crisis a call to action EthnDis 200717568ndash57313 Ervin RB Prevalence of metabolic syn-drome among adults 20 years of age and overby sex age race and ethnicity and body massindex United States 2003-2006 Natl HealthStat Rep 20091ndash714 Derby CA Wildman RP McGinn AP et alCardiovascular risk factor variation within a His-panic cohort SWAN the Study of WomenrsquosHealth Across the Nation Ethn Dis 201020396ndash40215 Allison MA Budoff MJ Wong NDBlumenthal RS Schreiner PJ Criqui MH Prev-alence of and risk factors for subclinical car-diovascular disease in selected US Hispanicethnic groups the Multi-Ethnic Study of Ath-erosclerosis Am J Epidemiol 2008167962ndash96916 Schargrodsky H Hernandez-Hernandez RChampagne BM et al CARMELA Study Investi-gators CARMELA assessment of cardiovascularrisk in seven Latin American cities Am J Med200812158ndash6517 Golden SH Brown A Cauley JA et al Healthdisparities in endocrine disorders biologicalclinical and nonclinical factorsdan EndocrineSociety scientific statement J Clin EndocrinolMetab 201297E1579ndashE163918 Katzmarzyk PT Bray GA Greenway FL et alEthnic-specific BMI and waist circumferencethresholds Obesity (Silver Spring) 2011191272ndash127819 Palaniappan LPWong EC Shin JJ FortmannSP Lauderdale DS Asian Americans havegreater prevalence of metabolic syndrome de-spite lower body mass index Int J Obes (Lond)201135393ndash40020 Sumner AE Sen S Ricks M Frempong BASebring NG Kushner H Determining the waistcircumference in African Americans which bestpredicts insulin resistance Obesity (SilverSpring) 200816841ndash846
21 Barbosa PJ Lessa I de Almeida Filho NMagalhatildees LB Araujo J Criteria for centralobesity in a Brazilian population impact onmet-abolic syndrome Arq Bras Cardiol 200687407ndash41422 Medina-Lezama J Pastorius CA Zea-Diaz Het al PREVENCION Investigators Optimal defini-tions for abdominal obesity and the metabolicsyndrome in Andean Hispanics the PREVENCIONstudy Diabetes Care 2010331385ndash138823 Perez M Casas JP Cubillos-Garzon LA et alUsing waist circumference as a screening tool toidentify Colombian subjects at cardiovascularrisk Eur J Cardiovasc Prev Rehabil 200310328ndash33524 Sanchez-Castillo CP Velazquez-Monroy OBerber A Lara-Esqueda A Tapia-Conyer RJames WP Encuesta Nacional de Salud (ENSA)2000 Working Group Anthropometric cutoffpoints for predicting chronic diseases in theMexican National Health Survey 2000 ObesRes 200311442ndash45125 Aschner P Buendıa R Brajkovich I et alDetermination of the cutoff point for waist cir-cumference that establishes the presence of ab-dominal obesity in Latin American men andwomen Diabetes Res Clin Pract 201193243ndash24726 Reaven GM Banting lecture 1988 Role ofinsulin resistance in human disease Diabetes1988371595ndash160727 Kahn R Buse J Ferrannini E SternM Amer-ican Diabetes Association European Associa-tion for the Study of Diabetes The metabolicsyndrome time for a critical appraisal jointstatement from the American Diabetes Associ-ation and the European Association for theStudy of Diabetes Diabetes Care 2005282289ndash230428 Grundy SM Metabolic syndrome pan-demic Arterioscler Thromb Vasc Biol 200828629ndash63629 Bruno G Fornengo P Segre O et al What isthe clinical usefulness of the metabolic syn-drome The Casale Monferrato study J Hyper-tens 2009272403ndash240830 Lemieux I Pascot A Couillard C et al Hy-pertriglyceridemic waist a marker of the ath-erogenic metabolic triad (hyperinsulinemiahyperapolipoprotein B small dense LDL) inmen Circulation 2000102179ndash18431 Rosenzweig JL Ferrannini E Grundy SMet al Endocrine Society Primary preventionof cardiovascular disease and type 2 diabetesin patients at metabolic risk an endocrine soci-ety clinical practice guideline J Clin EndocrinolMetab 2008933671ndash368932 Aguilera CM Olza J Gil A Genetic suscep-tibility to obesity and metabolic syndrome inchildhood Nutr Hosp 201328(Suppl 5)44ndash5533 Benyamin B Soslashrensen TI Schousboe KFenger M Visscher PM Kyvik KO Are therecommon genetic and environmental factors be-hind the endophenotypes associated with themetabolic syndrome Diabetologia 2007501880ndash188834 Dastani Z Hivert MF Timpson N et alNovel loci for adiponectin levels and their influ-ence on type 2 diabetes and metabolic traitsa multi-ethnic meta-analysis of 45891 individu-als PLoS Genet 20128e1002607
2398 Prevalence of Metabolic Syndrome in HispanicsLatinos Diabetes Care Volume 37 August 2014
35 Kristiansson K Perola M Tikkanen E et alGenome-wide screen for metabolic syndromesusceptibility loci reveals strong lipid genecontribution but no evidence for common ge-netic basis for clustering of metabolic syn-drome traits Circ Cardiovasc Genet 20125242ndash24936 Santos DM Katzmarzyk PT Diego VP et alGenotype by energy expenditure interaction
with metabolic syndrome traits the Portuguesehealthy family study PLoS One 20138e8041737 Hotamisligil GS Erbay E Nutrient sensingand inflammation in metabolic diseases NatRev Immunol 20088923ndash93438 Cani PDBibiloni R KnaufC et al Changes in gutmicrobiota control metabolic endotoxemia-inducedinflammation in high-fat diet-induced obesity anddiabetes in mice Diabetes 2008571470ndash1481
39 Turnbaugh PJ Ley RE Mahowald MAMagrini V Mardis ER Gordon JI An obesity-associated gut microbiome with increased ca-pacity for energy harvest Nature 20064441027ndash103140 Vijay-Kumar M Aitken JD Carvalho FAet al Metabolic syndrome and altered gut mi-crobiota in mice lacking Toll-like receptor 5 Sci-ence 2010328228ndash231
carediabetesjournalsorg Heiss and Associates 2399
women had a lower prevalence ofthe metabolic syndrome than PuertoRicans (15)The Cardiovascular Risk Factor Mul-
tiple Evaluation in Latin America(CARMELA) study (16) compared theprevalence of the metabolic syndromein residents 25ndash64 years of age (averageage 456 11 years) in seven Latin Amer-ican cities between 2003 and 2005(1600 examinees per city) The prev-alence of the metabolic syndrome de-fined according to the Adult TreatmentPanel III criteria age- and sex-adjustedto the sample from each city rangedfrom 14 in Quito Ecuador to 27 inMexico City Mexico For comparisonuse of the Adult Treatment Panel IIIcriteria in the 2003ndash2006 NHANESshowed a prevalence of 33 amongMexican American men and 41 amongMexican American women (13) Among
the sites surveyed by the CARMELAstudy Mexico City had the highest prev-alence of obesity (31) the metabolicsyndrome (27) and diabetes (9)The prevalence of the metabolic syn-drome observed in the HCHSSOL (34in men and 36 in women) is some-what higher than that estimated by theCARMELA study forMexico City and wasnotoriously higher than those observedin Barquisimeto Venezuela Bogota Co-lombia Buenos Aires Argentina LimaPeru Quito Ecuador and SantiagoChile
Other noteworthy findings from theHCHSSOL population are that 96 ofwomen and 73 of men with the meta-bolic syndrome had abdominal obesityusing the conventional 10288 cmthreshold The International DiabetesFederation conceived of the metabolicsyndrome based onwaist circumference
thresholds that differ for race and ethnicgroups and are considerably lower thanthose originally used in the NationalCholesterol Education Program criteriaIn its 2012 scientific statement on healthdisparities in endocrine disorders (17)the Endocrine Society called for thestudy and adoption of ethnic-specificcut points for central obesity to avoidmisclassification and for appropriaterisk management A number of reports(18ndash20) have raised concerns about thethreshold values for waist circumferenceused by the current definitions of abdom-inal obesity particularly as applied toAsian African American Polynesianand HispanicLatino populations Theprevalence of the metabolic syndromeaccording to different waist circumfer-ence thresholds has been publishedbased on NHANES 2003ndash2006 data (10)When less restrictive definitions of
Figure 1mdashPrevalence () of the number of individual cardiometabolic abnormalities in men (A) and women (B) in the HCHSSOL cohort by HispanicLatino background Error bars represent the SE
carediabetesjournalsorg Heiss and Associates 2395
central obesity were used prevalence es-timates increased as expected whereasassociations with cardiometabolic corre-lates were not visibly affectedRecognizing that the risk associated
with a given waist measurement differsacross populations waist circumferencethresholds recommended for ethnicCentral and South American popula-tions in the 2009 consensus Joint Scien-tific Statement (11) are$90 cm for menand $80 cm for women Instead thedata presented in this report are basedon the waist circumference thresholdsfamiliar to clinical practitioners in theUS ($102 cm in men and $88 cm inwomen) and are used as a commonmetric in reports from the NHANES(15) For comparability with studiesbased in other countries we replicatedour analyses using the$90 cm$80 cm
thresholds for men and women respec-tively recommended by the consensusJoint Scientific Statement (11) for ethnicCentral and South American popula-tions (these data are presented in Sup-plementary Table 3)
There have been several attempts toestablish waist circumference cutoff val-ues for abdominal obesity suitable towomen in Latin America drawing onvarious criteria such as detection of di-abetes (21) abnormal carotid artery in-tima media thickness (22) blood lipidprofile and other risk factors (23) andhypertension (24) Based on an area ofvisceral adipose tissue $100 cm2 mea-sured by computed tomography scan atthe 5th lumbar vertebra Aschner et al(25) recommended 94 cm for men and90 cm for women as the threshold ofabdominal obesity We examined the
impact of waist circumference thresholdvalues recommended by various au-thors for HispanicLatino populationson the prevalence of the metabolic syn-drome in the HCHSSOL populationsOverall their impact on the prevalenceof the metabolic syndrome in women inthe HCHSSOL was minor For examplethe use of the 90 cm threshold (insteadof 88 cm) as recommended by Aschneret al (25) reduced the prevalence of themetabolic syndrome in the women ofthe HCHSSOL samples by only 1ndash2
Various names and definitions havebeen applied to themetabolic syndromesince its original description by Reaven(26) as a cluster of metabolic risk factorsrelated to insulin resistance There isconsensus at this time that insulin resis-tance underlies the clustering of meta-bolic syndrome abnormalities and that
Figure 2mdashPrevalence () of individual cardiometabolic abnormalities in men (A) and women (B) with the metabolic syndrome in the HCHSSOLcohort by HispanicLatino background Error bars represent the SE
2396 Prevalence of Metabolic Syndrome in HispanicsLatinos Diabetes Care Volume 37 August 2014
these are associated with an increasedrisk of type 2 diabetes and cardiovascu-lar sequelae (7) Such associations arewell-established for the individual com-ponents of this syndrome regardless ofwhether they occur in isolation in com-bination or as a qualitatively definedsyndrome based on any three cardio-metabolic abnormalities Although themetabolic syndrome is embedded inclinical management guidelines thereis no consensus about the value of themetabolic syndrome as a tool to screenfor future risk of type 2 diabetes or car-diovascular diseases Whether thecardiometabolic risk factors that con-stitute the metabolic syndrome occuralone or in clusters evidence indicatesthat all such risk factors should be ad-dressed individually and managedeffectively (27) To our knowledge noevidence has been put forward to datefor nonadditivity of these metabolicfactors on the risk of type 2 diabetesincident cardiovascular disease ormortality (ie that the risk associatedwith the metabolic syndrome exceedsthe risk conferred by the sum of theindividual cardiometabolic risk factorsthat contributes to the syndrome)(27ndash29)To aid in the interpretation of waist
circumference Lemieux et al (30) pro-posed the concurrent measurement offasting triglycerides as an inexpensivemeans to screen for the atherogenicmetabolic dysregulation triad charac-terized by hyperinsulinemia elevatedapolipoprotein B level and small denseLDL-C In the HCHSSOL data fastingtriglyceride levels HDL-C levels systolicblood pressure and fasting glucoselevels each were associated with waistcircumference in a monotonically in-creasing (graded) linear fashion with-out indications of an inflection pointor a threshold for waist circumference(data not shown)As a qualitative approach to the
characterization of cardiometabolic ab-normalities associatedwith insulin resis-tance the metabolic syndrome hasbeen endorsed by major professionaland scientific organizations (7) Al-though the Endocrine Society endorsedthe use of the metabolic syndrome inclinical practice guidelines as a toolfor primary prevention of type 2 diabe-tes and cardiovascular disease its rel-evance still is subject to disagreement
(31) The lack of management or ther-apies specific to this syndromedasopposed to its individual componentabnormalitiesdmakes its use in clini-cal settings counterintuitive and theneed for sex- race- and ethnic group-specific thresholds for abdominal adi-posity for a ldquouniversalrdquo definition ofthe metabolic syndrome makes thisconstruct susceptible to misclassifica-tion and remains a source of contro-versy (25)
The metabolic syndrome traits areknown to have high heritability (30ndash70) and candidate gene approacheslinkage studies and genome-wide asso-ciation studies (32) have identified sus-ceptibility regions and loci for individualmetabolic syndrome components Theheritability of the metabolic syndromeis reportedly 30 although little ofthis heritability has been accounted for(33) Evidence for a common genetic un-derpinning of the broad spectrum of themetabolic syndrome has not been forth-coming despite reports from genome-wide association studies of geneticvariants associated with more than one ofthe metabolic abnormalities included inthe metabolic syndrome (34) Althoughwell-conducted studies failed to identifysignificant genetic susceptibility to mul-tiple metabolic syndrome components(35) the modulation of metabolic syn-drome expression by gene 3 environ-ment interactiondsuch as gene 3energy expenditure interaction (36)dwarrants further study
The clustering of metabolic impair-ments and the observed temporaltrends in the prevalence of the meta-bolic syndrome are thought to resultfrom excess food consumption andorreduced levels of physical activity Ex-cess nutrient intake leads to adiposityand activation of stress signaling whichin turn results in chronic activation ofproinflammatory kinase pathways thatdesensitize the metabolic response toinsulin (37) Development of the meta-bolic syndrome in humans is alsothought to be promoted by high levelsof saturated fats supported by animalmodels where high-fat diets inducedmetabolic disease (38) Recent workhas highlighted the role of intestinal mi-crobiota in promoting the cardiometa-bolic abnormalities associated with themetabolic syndrome such as adiposityby increasing the capacity of the host to
extract energy from ingested food (39)or through interaction with the innateimmune system in modulating inflam-matory signaling (40) Murine modelssuggest that the loss of Toll-like receptor5 function in the intestinal mucosachanges gut microbiota that inducelow-grade inflammatory signalingwhich may desensitize insulin receptorsignaling leading to excess food con-sumption and the associated cardiometa-bolic abnormalities of the metabolicsyndrome (40) The excess caloric con-sumption thought to drive the currentepidemic in metabolic syndrome maytherefore be influenced in part by host-microbiota interactions
In conclusion the prevalence of themetabolic syndrome and that of thecardiometabolic abnormalities that areconsidered to be components of themetabolic syndrome is high in His-panicLatinos and varies by sex andacross HispanicLatino backgroundsAbdominal adiposity predominates inHispanicLatino women in men thecharacterization by HispanicLatinobackgrounds shows heterogeneity inthe profiles of the component cardio-metabolic abnormalities The preven-tion of metabolic abnormalities andtheir clinical management may benefitfrom awareness of the diversity in car-diometabolic dysregulation by sex andHispanicLatino background This is re-inforced by the lack of prevention poli-cies or clinical management guidelinesthat are specific to the metabolic syn-drome per se as opposed to its compo-nent factors Efforts to control thepopulation burden of cardio-metabolicrisk among HispanicsLatinos will bene-fit from the observed differences by sexand HispanicLatino backgrounds
Acknowledgments The authors thank theHispanic Community Health StudyStudy ofLatinos (HCHSSOL) participants who gener-ously contributed their time and provided thestudy data The authors also thank the HCHSSOL staff members for their dedication andexpertise A complete list of staff and inves-tigators was published in the Annals of Epide-miology 201020642ndash649 and is also availableon the study website (httpwwwcsccunceduhchs)Funding The Hispanic Community HealthStudyStudy of Latinos (HCHSSOL) was carriedout as a collaborative study supported bycontracts from the National Heart Lung andBlood Institute (NHLBI) to the University ofNorth Carolina (N01-HC65233) the University
carediabetesjournalsorg Heiss and Associates 2397
of Miami (N01-HC65234) Albert Einstein Col-lege of Medicine (N01-HC65235) NorthwesternUniversity (N01-HC65236) and San Diego StateUniversity (N01-HC65237) The following insti-tutes centers or offices contribute to theHCHSSOL through a transfer of funds to theNHLBI National Center on Minority Health andHealth Disparities the National Institute onDeafness and Other Communication Disordersthe National Institute of Dental and CraniofacialResearch the National Institute of Diabetes andDigestive and Kidney Diseases the NationalInstitute of Neurological Disorders and Strokeand the Office of Dietary Supplements
The funding agency had a role in the design andconduct of the study in the collection analysisand interpretation of the data and in the reviewand approval of the manuscriptDuality of Interest No potential conflicts ofinterest relevant to this article were reportedAuthors Contributions GH researched theliterature interpreted the data and organizedand wrote the manuscript MLS NS MMLCC MC RK AG LG LL and LA-Scontributed to the interpretation of the dataand to the writing of the manuscript and wereinvolved in editing during manuscript prepara-tion YT conducted the statistical analysesprovided comments and had oversight of theverification of results GH is the guarantorof this work and as such had full access to allthe data in the study and takes responsibility forthe integrity of the data and the accuracy of thedata analysisPrior Presentation A set of preliminary datafrom this study was presented at the Epidemi-ology and PreventionNutrition Physical Activ-ity and Metabolism 2013 Scientific Sessions ofthe American Heart AssociationAmericanStroke Association New Orleans LA 19ndash22March 2013
References1 Hossain P Kawar B El Nahas M Obesity anddiabetes in the developing worldda growingchallenge N Engl J Med 2007356213ndash2152 BeydounMA Wang Y Gender-ethnic dispar-ity in BMI and waist circumference distributionshifts in US adults Obesity (Silver Spring) 200917169ndash1763 Olshansky SJ Passaro DJ Hershow RC et alA potential decline in life expectancy in theUnited States in the 21st century N Engl JMed 20053521138ndash11454 Ford ES Li C Sattar N Metabolic syndromeand incident diabetes current state of the evi-dence Diabetes Care 2008311898ndash19045 Ballantyne CM Hoogeveen RC McNeill AMet al Metabolic syndrome risk for cardiovascu-lar disease and diabetes in the ARIC study Int JObes (Lond) 200832(Suppl 2)S21ndashS246 Lakka HM Laaksonen DE Lakka TA et al Themetabolic syndrome and total and cardiovascu-lar disease mortality in middle-aged men JAMA20022882709ndash27167 Alberti KG Eckel RH Grundy SM et al In-ternational Diabetes Federation Task Force onEpidemiology and Prevention National HeartLung and Blood Institute American HeartAssociation World Heart Federation Interna-tional Atherosclerosis Society International As-sociation for the Study of Obesity Harmonizing
the metabolic syndrome a joint interim state-ment of the International Diabetes Federationtask force on epidemiology and prevention Na-tional Heart Lung and Blood Institute Ameri-can Heart Association World Heart FederationInternational Atherosclerosis Society and In-ternational Association for the Study of Obe-sity Circulation 20091201640ndash16458 Ford ES Giles WH Dietz WH Prevalence ofthe metabolic syndrome among US adultsfindings from the third National Health and Nu-trition Examination Survey JAMA 2002287356ndash3599 Lavange LM Kalsbeek WD Sorlie PD et alSample design and cohort selection in the His-panic Community Health StudyStudy of Lati-nos Ann Epidemiol 201020642ndash64910 Ford ES Li C Zhao G Prevalence and corre-lates of metabolic syndrome based on a harmo-nious definition among adults in the USJ Diabetes 20102180ndash19311 Daviglus ML Talavera GA Aviles-Santa MLet al Prevalence of major cardiovascular riskfactors and cardiovascular diseases among His-panicLatino individuals of diverse backgroundsin the United States JAMA 20123081775ndash178412 Davidson JA Kannel WB Lopez-Candales Aet al Avoiding the looming LatinoHispanic car-diovascular health crisis a call to action EthnDis 200717568ndash57313 Ervin RB Prevalence of metabolic syn-drome among adults 20 years of age and overby sex age race and ethnicity and body massindex United States 2003-2006 Natl HealthStat Rep 20091ndash714 Derby CA Wildman RP McGinn AP et alCardiovascular risk factor variation within a His-panic cohort SWAN the Study of WomenrsquosHealth Across the Nation Ethn Dis 201020396ndash40215 Allison MA Budoff MJ Wong NDBlumenthal RS Schreiner PJ Criqui MH Prev-alence of and risk factors for subclinical car-diovascular disease in selected US Hispanicethnic groups the Multi-Ethnic Study of Ath-erosclerosis Am J Epidemiol 2008167962ndash96916 Schargrodsky H Hernandez-Hernandez RChampagne BM et al CARMELA Study Investi-gators CARMELA assessment of cardiovascularrisk in seven Latin American cities Am J Med200812158ndash6517 Golden SH Brown A Cauley JA et al Healthdisparities in endocrine disorders biologicalclinical and nonclinical factorsdan EndocrineSociety scientific statement J Clin EndocrinolMetab 201297E1579ndashE163918 Katzmarzyk PT Bray GA Greenway FL et alEthnic-specific BMI and waist circumferencethresholds Obesity (Silver Spring) 2011191272ndash127819 Palaniappan LPWong EC Shin JJ FortmannSP Lauderdale DS Asian Americans havegreater prevalence of metabolic syndrome de-spite lower body mass index Int J Obes (Lond)201135393ndash40020 Sumner AE Sen S Ricks M Frempong BASebring NG Kushner H Determining the waistcircumference in African Americans which bestpredicts insulin resistance Obesity (SilverSpring) 200816841ndash846
21 Barbosa PJ Lessa I de Almeida Filho NMagalhatildees LB Araujo J Criteria for centralobesity in a Brazilian population impact onmet-abolic syndrome Arq Bras Cardiol 200687407ndash41422 Medina-Lezama J Pastorius CA Zea-Diaz Het al PREVENCION Investigators Optimal defini-tions for abdominal obesity and the metabolicsyndrome in Andean Hispanics the PREVENCIONstudy Diabetes Care 2010331385ndash138823 Perez M Casas JP Cubillos-Garzon LA et alUsing waist circumference as a screening tool toidentify Colombian subjects at cardiovascularrisk Eur J Cardiovasc Prev Rehabil 200310328ndash33524 Sanchez-Castillo CP Velazquez-Monroy OBerber A Lara-Esqueda A Tapia-Conyer RJames WP Encuesta Nacional de Salud (ENSA)2000 Working Group Anthropometric cutoffpoints for predicting chronic diseases in theMexican National Health Survey 2000 ObesRes 200311442ndash45125 Aschner P Buendıa R Brajkovich I et alDetermination of the cutoff point for waist cir-cumference that establishes the presence of ab-dominal obesity in Latin American men andwomen Diabetes Res Clin Pract 201193243ndash24726 Reaven GM Banting lecture 1988 Role ofinsulin resistance in human disease Diabetes1988371595ndash160727 Kahn R Buse J Ferrannini E SternM Amer-ican Diabetes Association European Associa-tion for the Study of Diabetes The metabolicsyndrome time for a critical appraisal jointstatement from the American Diabetes Associ-ation and the European Association for theStudy of Diabetes Diabetes Care 2005282289ndash230428 Grundy SM Metabolic syndrome pan-demic Arterioscler Thromb Vasc Biol 200828629ndash63629 Bruno G Fornengo P Segre O et al What isthe clinical usefulness of the metabolic syn-drome The Casale Monferrato study J Hyper-tens 2009272403ndash240830 Lemieux I Pascot A Couillard C et al Hy-pertriglyceridemic waist a marker of the ath-erogenic metabolic triad (hyperinsulinemiahyperapolipoprotein B small dense LDL) inmen Circulation 2000102179ndash18431 Rosenzweig JL Ferrannini E Grundy SMet al Endocrine Society Primary preventionof cardiovascular disease and type 2 diabetesin patients at metabolic risk an endocrine soci-ety clinical practice guideline J Clin EndocrinolMetab 2008933671ndash368932 Aguilera CM Olza J Gil A Genetic suscep-tibility to obesity and metabolic syndrome inchildhood Nutr Hosp 201328(Suppl 5)44ndash5533 Benyamin B Soslashrensen TI Schousboe KFenger M Visscher PM Kyvik KO Are therecommon genetic and environmental factors be-hind the endophenotypes associated with themetabolic syndrome Diabetologia 2007501880ndash188834 Dastani Z Hivert MF Timpson N et alNovel loci for adiponectin levels and their influ-ence on type 2 diabetes and metabolic traitsa multi-ethnic meta-analysis of 45891 individu-als PLoS Genet 20128e1002607
2398 Prevalence of Metabolic Syndrome in HispanicsLatinos Diabetes Care Volume 37 August 2014
35 Kristiansson K Perola M Tikkanen E et alGenome-wide screen for metabolic syndromesusceptibility loci reveals strong lipid genecontribution but no evidence for common ge-netic basis for clustering of metabolic syn-drome traits Circ Cardiovasc Genet 20125242ndash24936 Santos DM Katzmarzyk PT Diego VP et alGenotype by energy expenditure interaction
with metabolic syndrome traits the Portuguesehealthy family study PLoS One 20138e8041737 Hotamisligil GS Erbay E Nutrient sensingand inflammation in metabolic diseases NatRev Immunol 20088923ndash93438 Cani PDBibiloni R KnaufC et al Changes in gutmicrobiota control metabolic endotoxemia-inducedinflammation in high-fat diet-induced obesity anddiabetes in mice Diabetes 2008571470ndash1481
39 Turnbaugh PJ Ley RE Mahowald MAMagrini V Mardis ER Gordon JI An obesity-associated gut microbiome with increased ca-pacity for energy harvest Nature 20064441027ndash103140 Vijay-Kumar M Aitken JD Carvalho FAet al Metabolic syndrome and altered gut mi-crobiota in mice lacking Toll-like receptor 5 Sci-ence 2010328228ndash231
carediabetesjournalsorg Heiss and Associates 2399
central obesity were used prevalence es-timates increased as expected whereasassociations with cardiometabolic corre-lates were not visibly affectedRecognizing that the risk associated
with a given waist measurement differsacross populations waist circumferencethresholds recommended for ethnicCentral and South American popula-tions in the 2009 consensus Joint Scien-tific Statement (11) are$90 cm for menand $80 cm for women Instead thedata presented in this report are basedon the waist circumference thresholdsfamiliar to clinical practitioners in theUS ($102 cm in men and $88 cm inwomen) and are used as a commonmetric in reports from the NHANES(15) For comparability with studiesbased in other countries we replicatedour analyses using the$90 cm$80 cm
thresholds for men and women respec-tively recommended by the consensusJoint Scientific Statement (11) for ethnicCentral and South American popula-tions (these data are presented in Sup-plementary Table 3)
There have been several attempts toestablish waist circumference cutoff val-ues for abdominal obesity suitable towomen in Latin America drawing onvarious criteria such as detection of di-abetes (21) abnormal carotid artery in-tima media thickness (22) blood lipidprofile and other risk factors (23) andhypertension (24) Based on an area ofvisceral adipose tissue $100 cm2 mea-sured by computed tomography scan atthe 5th lumbar vertebra Aschner et al(25) recommended 94 cm for men and90 cm for women as the threshold ofabdominal obesity We examined the
impact of waist circumference thresholdvalues recommended by various au-thors for HispanicLatino populationson the prevalence of the metabolic syn-drome in the HCHSSOL populationsOverall their impact on the prevalenceof the metabolic syndrome in women inthe HCHSSOL was minor For examplethe use of the 90 cm threshold (insteadof 88 cm) as recommended by Aschneret al (25) reduced the prevalence of themetabolic syndrome in the women ofthe HCHSSOL samples by only 1ndash2
Various names and definitions havebeen applied to themetabolic syndromesince its original description by Reaven(26) as a cluster of metabolic risk factorsrelated to insulin resistance There isconsensus at this time that insulin resis-tance underlies the clustering of meta-bolic syndrome abnormalities and that
Figure 2mdashPrevalence () of individual cardiometabolic abnormalities in men (A) and women (B) with the metabolic syndrome in the HCHSSOLcohort by HispanicLatino background Error bars represent the SE
2396 Prevalence of Metabolic Syndrome in HispanicsLatinos Diabetes Care Volume 37 August 2014
these are associated with an increasedrisk of type 2 diabetes and cardiovascu-lar sequelae (7) Such associations arewell-established for the individual com-ponents of this syndrome regardless ofwhether they occur in isolation in com-bination or as a qualitatively definedsyndrome based on any three cardio-metabolic abnormalities Although themetabolic syndrome is embedded inclinical management guidelines thereis no consensus about the value of themetabolic syndrome as a tool to screenfor future risk of type 2 diabetes or car-diovascular diseases Whether thecardiometabolic risk factors that con-stitute the metabolic syndrome occuralone or in clusters evidence indicatesthat all such risk factors should be ad-dressed individually and managedeffectively (27) To our knowledge noevidence has been put forward to datefor nonadditivity of these metabolicfactors on the risk of type 2 diabetesincident cardiovascular disease ormortality (ie that the risk associatedwith the metabolic syndrome exceedsthe risk conferred by the sum of theindividual cardiometabolic risk factorsthat contributes to the syndrome)(27ndash29)To aid in the interpretation of waist
circumference Lemieux et al (30) pro-posed the concurrent measurement offasting triglycerides as an inexpensivemeans to screen for the atherogenicmetabolic dysregulation triad charac-terized by hyperinsulinemia elevatedapolipoprotein B level and small denseLDL-C In the HCHSSOL data fastingtriglyceride levels HDL-C levels systolicblood pressure and fasting glucoselevels each were associated with waistcircumference in a monotonically in-creasing (graded) linear fashion with-out indications of an inflection pointor a threshold for waist circumference(data not shown)As a qualitative approach to the
characterization of cardiometabolic ab-normalities associatedwith insulin resis-tance the metabolic syndrome hasbeen endorsed by major professionaland scientific organizations (7) Al-though the Endocrine Society endorsedthe use of the metabolic syndrome inclinical practice guidelines as a toolfor primary prevention of type 2 diabe-tes and cardiovascular disease its rel-evance still is subject to disagreement
(31) The lack of management or ther-apies specific to this syndromedasopposed to its individual componentabnormalitiesdmakes its use in clini-cal settings counterintuitive and theneed for sex- race- and ethnic group-specific thresholds for abdominal adi-posity for a ldquouniversalrdquo definition ofthe metabolic syndrome makes thisconstruct susceptible to misclassifica-tion and remains a source of contro-versy (25)
The metabolic syndrome traits areknown to have high heritability (30ndash70) and candidate gene approacheslinkage studies and genome-wide asso-ciation studies (32) have identified sus-ceptibility regions and loci for individualmetabolic syndrome components Theheritability of the metabolic syndromeis reportedly 30 although little ofthis heritability has been accounted for(33) Evidence for a common genetic un-derpinning of the broad spectrum of themetabolic syndrome has not been forth-coming despite reports from genome-wide association studies of geneticvariants associated with more than one ofthe metabolic abnormalities included inthe metabolic syndrome (34) Althoughwell-conducted studies failed to identifysignificant genetic susceptibility to mul-tiple metabolic syndrome components(35) the modulation of metabolic syn-drome expression by gene 3 environ-ment interactiondsuch as gene 3energy expenditure interaction (36)dwarrants further study
The clustering of metabolic impair-ments and the observed temporaltrends in the prevalence of the meta-bolic syndrome are thought to resultfrom excess food consumption andorreduced levels of physical activity Ex-cess nutrient intake leads to adiposityand activation of stress signaling whichin turn results in chronic activation ofproinflammatory kinase pathways thatdesensitize the metabolic response toinsulin (37) Development of the meta-bolic syndrome in humans is alsothought to be promoted by high levelsof saturated fats supported by animalmodels where high-fat diets inducedmetabolic disease (38) Recent workhas highlighted the role of intestinal mi-crobiota in promoting the cardiometa-bolic abnormalities associated with themetabolic syndrome such as adiposityby increasing the capacity of the host to
extract energy from ingested food (39)or through interaction with the innateimmune system in modulating inflam-matory signaling (40) Murine modelssuggest that the loss of Toll-like receptor5 function in the intestinal mucosachanges gut microbiota that inducelow-grade inflammatory signalingwhich may desensitize insulin receptorsignaling leading to excess food con-sumption and the associated cardiometa-bolic abnormalities of the metabolicsyndrome (40) The excess caloric con-sumption thought to drive the currentepidemic in metabolic syndrome maytherefore be influenced in part by host-microbiota interactions
In conclusion the prevalence of themetabolic syndrome and that of thecardiometabolic abnormalities that areconsidered to be components of themetabolic syndrome is high in His-panicLatinos and varies by sex andacross HispanicLatino backgroundsAbdominal adiposity predominates inHispanicLatino women in men thecharacterization by HispanicLatinobackgrounds shows heterogeneity inthe profiles of the component cardio-metabolic abnormalities The preven-tion of metabolic abnormalities andtheir clinical management may benefitfrom awareness of the diversity in car-diometabolic dysregulation by sex andHispanicLatino background This is re-inforced by the lack of prevention poli-cies or clinical management guidelinesthat are specific to the metabolic syn-drome per se as opposed to its compo-nent factors Efforts to control thepopulation burden of cardio-metabolicrisk among HispanicsLatinos will bene-fit from the observed differences by sexand HispanicLatino backgrounds
Acknowledgments The authors thank theHispanic Community Health StudyStudy ofLatinos (HCHSSOL) participants who gener-ously contributed their time and provided thestudy data The authors also thank the HCHSSOL staff members for their dedication andexpertise A complete list of staff and inves-tigators was published in the Annals of Epide-miology 201020642ndash649 and is also availableon the study website (httpwwwcsccunceduhchs)Funding The Hispanic Community HealthStudyStudy of Latinos (HCHSSOL) was carriedout as a collaborative study supported bycontracts from the National Heart Lung andBlood Institute (NHLBI) to the University ofNorth Carolina (N01-HC65233) the University
carediabetesjournalsorg Heiss and Associates 2397
of Miami (N01-HC65234) Albert Einstein Col-lege of Medicine (N01-HC65235) NorthwesternUniversity (N01-HC65236) and San Diego StateUniversity (N01-HC65237) The following insti-tutes centers or offices contribute to theHCHSSOL through a transfer of funds to theNHLBI National Center on Minority Health andHealth Disparities the National Institute onDeafness and Other Communication Disordersthe National Institute of Dental and CraniofacialResearch the National Institute of Diabetes andDigestive and Kidney Diseases the NationalInstitute of Neurological Disorders and Strokeand the Office of Dietary Supplements
The funding agency had a role in the design andconduct of the study in the collection analysisand interpretation of the data and in the reviewand approval of the manuscriptDuality of Interest No potential conflicts ofinterest relevant to this article were reportedAuthors Contributions GH researched theliterature interpreted the data and organizedand wrote the manuscript MLS NS MMLCC MC RK AG LG LL and LA-Scontributed to the interpretation of the dataand to the writing of the manuscript and wereinvolved in editing during manuscript prepara-tion YT conducted the statistical analysesprovided comments and had oversight of theverification of results GH is the guarantorof this work and as such had full access to allthe data in the study and takes responsibility forthe integrity of the data and the accuracy of thedata analysisPrior Presentation A set of preliminary datafrom this study was presented at the Epidemi-ology and PreventionNutrition Physical Activ-ity and Metabolism 2013 Scientific Sessions ofthe American Heart AssociationAmericanStroke Association New Orleans LA 19ndash22March 2013
References1 Hossain P Kawar B El Nahas M Obesity anddiabetes in the developing worldda growingchallenge N Engl J Med 2007356213ndash2152 BeydounMA Wang Y Gender-ethnic dispar-ity in BMI and waist circumference distributionshifts in US adults Obesity (Silver Spring) 200917169ndash1763 Olshansky SJ Passaro DJ Hershow RC et alA potential decline in life expectancy in theUnited States in the 21st century N Engl JMed 20053521138ndash11454 Ford ES Li C Sattar N Metabolic syndromeand incident diabetes current state of the evi-dence Diabetes Care 2008311898ndash19045 Ballantyne CM Hoogeveen RC McNeill AMet al Metabolic syndrome risk for cardiovascu-lar disease and diabetes in the ARIC study Int JObes (Lond) 200832(Suppl 2)S21ndashS246 Lakka HM Laaksonen DE Lakka TA et al Themetabolic syndrome and total and cardiovascu-lar disease mortality in middle-aged men JAMA20022882709ndash27167 Alberti KG Eckel RH Grundy SM et al In-ternational Diabetes Federation Task Force onEpidemiology and Prevention National HeartLung and Blood Institute American HeartAssociation World Heart Federation Interna-tional Atherosclerosis Society International As-sociation for the Study of Obesity Harmonizing
the metabolic syndrome a joint interim state-ment of the International Diabetes Federationtask force on epidemiology and prevention Na-tional Heart Lung and Blood Institute Ameri-can Heart Association World Heart FederationInternational Atherosclerosis Society and In-ternational Association for the Study of Obe-sity Circulation 20091201640ndash16458 Ford ES Giles WH Dietz WH Prevalence ofthe metabolic syndrome among US adultsfindings from the third National Health and Nu-trition Examination Survey JAMA 2002287356ndash3599 Lavange LM Kalsbeek WD Sorlie PD et alSample design and cohort selection in the His-panic Community Health StudyStudy of Lati-nos Ann Epidemiol 201020642ndash64910 Ford ES Li C Zhao G Prevalence and corre-lates of metabolic syndrome based on a harmo-nious definition among adults in the USJ Diabetes 20102180ndash19311 Daviglus ML Talavera GA Aviles-Santa MLet al Prevalence of major cardiovascular riskfactors and cardiovascular diseases among His-panicLatino individuals of diverse backgroundsin the United States JAMA 20123081775ndash178412 Davidson JA Kannel WB Lopez-Candales Aet al Avoiding the looming LatinoHispanic car-diovascular health crisis a call to action EthnDis 200717568ndash57313 Ervin RB Prevalence of metabolic syn-drome among adults 20 years of age and overby sex age race and ethnicity and body massindex United States 2003-2006 Natl HealthStat Rep 20091ndash714 Derby CA Wildman RP McGinn AP et alCardiovascular risk factor variation within a His-panic cohort SWAN the Study of WomenrsquosHealth Across the Nation Ethn Dis 201020396ndash40215 Allison MA Budoff MJ Wong NDBlumenthal RS Schreiner PJ Criqui MH Prev-alence of and risk factors for subclinical car-diovascular disease in selected US Hispanicethnic groups the Multi-Ethnic Study of Ath-erosclerosis Am J Epidemiol 2008167962ndash96916 Schargrodsky H Hernandez-Hernandez RChampagne BM et al CARMELA Study Investi-gators CARMELA assessment of cardiovascularrisk in seven Latin American cities Am J Med200812158ndash6517 Golden SH Brown A Cauley JA et al Healthdisparities in endocrine disorders biologicalclinical and nonclinical factorsdan EndocrineSociety scientific statement J Clin EndocrinolMetab 201297E1579ndashE163918 Katzmarzyk PT Bray GA Greenway FL et alEthnic-specific BMI and waist circumferencethresholds Obesity (Silver Spring) 2011191272ndash127819 Palaniappan LPWong EC Shin JJ FortmannSP Lauderdale DS Asian Americans havegreater prevalence of metabolic syndrome de-spite lower body mass index Int J Obes (Lond)201135393ndash40020 Sumner AE Sen S Ricks M Frempong BASebring NG Kushner H Determining the waistcircumference in African Americans which bestpredicts insulin resistance Obesity (SilverSpring) 200816841ndash846
21 Barbosa PJ Lessa I de Almeida Filho NMagalhatildees LB Araujo J Criteria for centralobesity in a Brazilian population impact onmet-abolic syndrome Arq Bras Cardiol 200687407ndash41422 Medina-Lezama J Pastorius CA Zea-Diaz Het al PREVENCION Investigators Optimal defini-tions for abdominal obesity and the metabolicsyndrome in Andean Hispanics the PREVENCIONstudy Diabetes Care 2010331385ndash138823 Perez M Casas JP Cubillos-Garzon LA et alUsing waist circumference as a screening tool toidentify Colombian subjects at cardiovascularrisk Eur J Cardiovasc Prev Rehabil 200310328ndash33524 Sanchez-Castillo CP Velazquez-Monroy OBerber A Lara-Esqueda A Tapia-Conyer RJames WP Encuesta Nacional de Salud (ENSA)2000 Working Group Anthropometric cutoffpoints for predicting chronic diseases in theMexican National Health Survey 2000 ObesRes 200311442ndash45125 Aschner P Buendıa R Brajkovich I et alDetermination of the cutoff point for waist cir-cumference that establishes the presence of ab-dominal obesity in Latin American men andwomen Diabetes Res Clin Pract 201193243ndash24726 Reaven GM Banting lecture 1988 Role ofinsulin resistance in human disease Diabetes1988371595ndash160727 Kahn R Buse J Ferrannini E SternM Amer-ican Diabetes Association European Associa-tion for the Study of Diabetes The metabolicsyndrome time for a critical appraisal jointstatement from the American Diabetes Associ-ation and the European Association for theStudy of Diabetes Diabetes Care 2005282289ndash230428 Grundy SM Metabolic syndrome pan-demic Arterioscler Thromb Vasc Biol 200828629ndash63629 Bruno G Fornengo P Segre O et al What isthe clinical usefulness of the metabolic syn-drome The Casale Monferrato study J Hyper-tens 2009272403ndash240830 Lemieux I Pascot A Couillard C et al Hy-pertriglyceridemic waist a marker of the ath-erogenic metabolic triad (hyperinsulinemiahyperapolipoprotein B small dense LDL) inmen Circulation 2000102179ndash18431 Rosenzweig JL Ferrannini E Grundy SMet al Endocrine Society Primary preventionof cardiovascular disease and type 2 diabetesin patients at metabolic risk an endocrine soci-ety clinical practice guideline J Clin EndocrinolMetab 2008933671ndash368932 Aguilera CM Olza J Gil A Genetic suscep-tibility to obesity and metabolic syndrome inchildhood Nutr Hosp 201328(Suppl 5)44ndash5533 Benyamin B Soslashrensen TI Schousboe KFenger M Visscher PM Kyvik KO Are therecommon genetic and environmental factors be-hind the endophenotypes associated with themetabolic syndrome Diabetologia 2007501880ndash188834 Dastani Z Hivert MF Timpson N et alNovel loci for adiponectin levels and their influ-ence on type 2 diabetes and metabolic traitsa multi-ethnic meta-analysis of 45891 individu-als PLoS Genet 20128e1002607
2398 Prevalence of Metabolic Syndrome in HispanicsLatinos Diabetes Care Volume 37 August 2014
35 Kristiansson K Perola M Tikkanen E et alGenome-wide screen for metabolic syndromesusceptibility loci reveals strong lipid genecontribution but no evidence for common ge-netic basis for clustering of metabolic syn-drome traits Circ Cardiovasc Genet 20125242ndash24936 Santos DM Katzmarzyk PT Diego VP et alGenotype by energy expenditure interaction
with metabolic syndrome traits the Portuguesehealthy family study PLoS One 20138e8041737 Hotamisligil GS Erbay E Nutrient sensingand inflammation in metabolic diseases NatRev Immunol 20088923ndash93438 Cani PDBibiloni R KnaufC et al Changes in gutmicrobiota control metabolic endotoxemia-inducedinflammation in high-fat diet-induced obesity anddiabetes in mice Diabetes 2008571470ndash1481
39 Turnbaugh PJ Ley RE Mahowald MAMagrini V Mardis ER Gordon JI An obesity-associated gut microbiome with increased ca-pacity for energy harvest Nature 20064441027ndash103140 Vijay-Kumar M Aitken JD Carvalho FAet al Metabolic syndrome and altered gut mi-crobiota in mice lacking Toll-like receptor 5 Sci-ence 2010328228ndash231
carediabetesjournalsorg Heiss and Associates 2399
these are associated with an increasedrisk of type 2 diabetes and cardiovascu-lar sequelae (7) Such associations arewell-established for the individual com-ponents of this syndrome regardless ofwhether they occur in isolation in com-bination or as a qualitatively definedsyndrome based on any three cardio-metabolic abnormalities Although themetabolic syndrome is embedded inclinical management guidelines thereis no consensus about the value of themetabolic syndrome as a tool to screenfor future risk of type 2 diabetes or car-diovascular diseases Whether thecardiometabolic risk factors that con-stitute the metabolic syndrome occuralone or in clusters evidence indicatesthat all such risk factors should be ad-dressed individually and managedeffectively (27) To our knowledge noevidence has been put forward to datefor nonadditivity of these metabolicfactors on the risk of type 2 diabetesincident cardiovascular disease ormortality (ie that the risk associatedwith the metabolic syndrome exceedsthe risk conferred by the sum of theindividual cardiometabolic risk factorsthat contributes to the syndrome)(27ndash29)To aid in the interpretation of waist
circumference Lemieux et al (30) pro-posed the concurrent measurement offasting triglycerides as an inexpensivemeans to screen for the atherogenicmetabolic dysregulation triad charac-terized by hyperinsulinemia elevatedapolipoprotein B level and small denseLDL-C In the HCHSSOL data fastingtriglyceride levels HDL-C levels systolicblood pressure and fasting glucoselevels each were associated with waistcircumference in a monotonically in-creasing (graded) linear fashion with-out indications of an inflection pointor a threshold for waist circumference(data not shown)As a qualitative approach to the
characterization of cardiometabolic ab-normalities associatedwith insulin resis-tance the metabolic syndrome hasbeen endorsed by major professionaland scientific organizations (7) Al-though the Endocrine Society endorsedthe use of the metabolic syndrome inclinical practice guidelines as a toolfor primary prevention of type 2 diabe-tes and cardiovascular disease its rel-evance still is subject to disagreement
(31) The lack of management or ther-apies specific to this syndromedasopposed to its individual componentabnormalitiesdmakes its use in clini-cal settings counterintuitive and theneed for sex- race- and ethnic group-specific thresholds for abdominal adi-posity for a ldquouniversalrdquo definition ofthe metabolic syndrome makes thisconstruct susceptible to misclassifica-tion and remains a source of contro-versy (25)
The metabolic syndrome traits areknown to have high heritability (30ndash70) and candidate gene approacheslinkage studies and genome-wide asso-ciation studies (32) have identified sus-ceptibility regions and loci for individualmetabolic syndrome components Theheritability of the metabolic syndromeis reportedly 30 although little ofthis heritability has been accounted for(33) Evidence for a common genetic un-derpinning of the broad spectrum of themetabolic syndrome has not been forth-coming despite reports from genome-wide association studies of geneticvariants associated with more than one ofthe metabolic abnormalities included inthe metabolic syndrome (34) Althoughwell-conducted studies failed to identifysignificant genetic susceptibility to mul-tiple metabolic syndrome components(35) the modulation of metabolic syn-drome expression by gene 3 environ-ment interactiondsuch as gene 3energy expenditure interaction (36)dwarrants further study
The clustering of metabolic impair-ments and the observed temporaltrends in the prevalence of the meta-bolic syndrome are thought to resultfrom excess food consumption andorreduced levels of physical activity Ex-cess nutrient intake leads to adiposityand activation of stress signaling whichin turn results in chronic activation ofproinflammatory kinase pathways thatdesensitize the metabolic response toinsulin (37) Development of the meta-bolic syndrome in humans is alsothought to be promoted by high levelsof saturated fats supported by animalmodels where high-fat diets inducedmetabolic disease (38) Recent workhas highlighted the role of intestinal mi-crobiota in promoting the cardiometa-bolic abnormalities associated with themetabolic syndrome such as adiposityby increasing the capacity of the host to
extract energy from ingested food (39)or through interaction with the innateimmune system in modulating inflam-matory signaling (40) Murine modelssuggest that the loss of Toll-like receptor5 function in the intestinal mucosachanges gut microbiota that inducelow-grade inflammatory signalingwhich may desensitize insulin receptorsignaling leading to excess food con-sumption and the associated cardiometa-bolic abnormalities of the metabolicsyndrome (40) The excess caloric con-sumption thought to drive the currentepidemic in metabolic syndrome maytherefore be influenced in part by host-microbiota interactions
In conclusion the prevalence of themetabolic syndrome and that of thecardiometabolic abnormalities that areconsidered to be components of themetabolic syndrome is high in His-panicLatinos and varies by sex andacross HispanicLatino backgroundsAbdominal adiposity predominates inHispanicLatino women in men thecharacterization by HispanicLatinobackgrounds shows heterogeneity inthe profiles of the component cardio-metabolic abnormalities The preven-tion of metabolic abnormalities andtheir clinical management may benefitfrom awareness of the diversity in car-diometabolic dysregulation by sex andHispanicLatino background This is re-inforced by the lack of prevention poli-cies or clinical management guidelinesthat are specific to the metabolic syn-drome per se as opposed to its compo-nent factors Efforts to control thepopulation burden of cardio-metabolicrisk among HispanicsLatinos will bene-fit from the observed differences by sexand HispanicLatino backgrounds
Acknowledgments The authors thank theHispanic Community Health StudyStudy ofLatinos (HCHSSOL) participants who gener-ously contributed their time and provided thestudy data The authors also thank the HCHSSOL staff members for their dedication andexpertise A complete list of staff and inves-tigators was published in the Annals of Epide-miology 201020642ndash649 and is also availableon the study website (httpwwwcsccunceduhchs)Funding The Hispanic Community HealthStudyStudy of Latinos (HCHSSOL) was carriedout as a collaborative study supported bycontracts from the National Heart Lung andBlood Institute (NHLBI) to the University ofNorth Carolina (N01-HC65233) the University
carediabetesjournalsorg Heiss and Associates 2397
of Miami (N01-HC65234) Albert Einstein Col-lege of Medicine (N01-HC65235) NorthwesternUniversity (N01-HC65236) and San Diego StateUniversity (N01-HC65237) The following insti-tutes centers or offices contribute to theHCHSSOL through a transfer of funds to theNHLBI National Center on Minority Health andHealth Disparities the National Institute onDeafness and Other Communication Disordersthe National Institute of Dental and CraniofacialResearch the National Institute of Diabetes andDigestive and Kidney Diseases the NationalInstitute of Neurological Disorders and Strokeand the Office of Dietary Supplements
The funding agency had a role in the design andconduct of the study in the collection analysisand interpretation of the data and in the reviewand approval of the manuscriptDuality of Interest No potential conflicts ofinterest relevant to this article were reportedAuthors Contributions GH researched theliterature interpreted the data and organizedand wrote the manuscript MLS NS MMLCC MC RK AG LG LL and LA-Scontributed to the interpretation of the dataand to the writing of the manuscript and wereinvolved in editing during manuscript prepara-tion YT conducted the statistical analysesprovided comments and had oversight of theverification of results GH is the guarantorof this work and as such had full access to allthe data in the study and takes responsibility forthe integrity of the data and the accuracy of thedata analysisPrior Presentation A set of preliminary datafrom this study was presented at the Epidemi-ology and PreventionNutrition Physical Activ-ity and Metabolism 2013 Scientific Sessions ofthe American Heart AssociationAmericanStroke Association New Orleans LA 19ndash22March 2013
References1 Hossain P Kawar B El Nahas M Obesity anddiabetes in the developing worldda growingchallenge N Engl J Med 2007356213ndash2152 BeydounMA Wang Y Gender-ethnic dispar-ity in BMI and waist circumference distributionshifts in US adults Obesity (Silver Spring) 200917169ndash1763 Olshansky SJ Passaro DJ Hershow RC et alA potential decline in life expectancy in theUnited States in the 21st century N Engl JMed 20053521138ndash11454 Ford ES Li C Sattar N Metabolic syndromeand incident diabetes current state of the evi-dence Diabetes Care 2008311898ndash19045 Ballantyne CM Hoogeveen RC McNeill AMet al Metabolic syndrome risk for cardiovascu-lar disease and diabetes in the ARIC study Int JObes (Lond) 200832(Suppl 2)S21ndashS246 Lakka HM Laaksonen DE Lakka TA et al Themetabolic syndrome and total and cardiovascu-lar disease mortality in middle-aged men JAMA20022882709ndash27167 Alberti KG Eckel RH Grundy SM et al In-ternational Diabetes Federation Task Force onEpidemiology and Prevention National HeartLung and Blood Institute American HeartAssociation World Heart Federation Interna-tional Atherosclerosis Society International As-sociation for the Study of Obesity Harmonizing
the metabolic syndrome a joint interim state-ment of the International Diabetes Federationtask force on epidemiology and prevention Na-tional Heart Lung and Blood Institute Ameri-can Heart Association World Heart FederationInternational Atherosclerosis Society and In-ternational Association for the Study of Obe-sity Circulation 20091201640ndash16458 Ford ES Giles WH Dietz WH Prevalence ofthe metabolic syndrome among US adultsfindings from the third National Health and Nu-trition Examination Survey JAMA 2002287356ndash3599 Lavange LM Kalsbeek WD Sorlie PD et alSample design and cohort selection in the His-panic Community Health StudyStudy of Lati-nos Ann Epidemiol 201020642ndash64910 Ford ES Li C Zhao G Prevalence and corre-lates of metabolic syndrome based on a harmo-nious definition among adults in the USJ Diabetes 20102180ndash19311 Daviglus ML Talavera GA Aviles-Santa MLet al Prevalence of major cardiovascular riskfactors and cardiovascular diseases among His-panicLatino individuals of diverse backgroundsin the United States JAMA 20123081775ndash178412 Davidson JA Kannel WB Lopez-Candales Aet al Avoiding the looming LatinoHispanic car-diovascular health crisis a call to action EthnDis 200717568ndash57313 Ervin RB Prevalence of metabolic syn-drome among adults 20 years of age and overby sex age race and ethnicity and body massindex United States 2003-2006 Natl HealthStat Rep 20091ndash714 Derby CA Wildman RP McGinn AP et alCardiovascular risk factor variation within a His-panic cohort SWAN the Study of WomenrsquosHealth Across the Nation Ethn Dis 201020396ndash40215 Allison MA Budoff MJ Wong NDBlumenthal RS Schreiner PJ Criqui MH Prev-alence of and risk factors for subclinical car-diovascular disease in selected US Hispanicethnic groups the Multi-Ethnic Study of Ath-erosclerosis Am J Epidemiol 2008167962ndash96916 Schargrodsky H Hernandez-Hernandez RChampagne BM et al CARMELA Study Investi-gators CARMELA assessment of cardiovascularrisk in seven Latin American cities Am J Med200812158ndash6517 Golden SH Brown A Cauley JA et al Healthdisparities in endocrine disorders biologicalclinical and nonclinical factorsdan EndocrineSociety scientific statement J Clin EndocrinolMetab 201297E1579ndashE163918 Katzmarzyk PT Bray GA Greenway FL et alEthnic-specific BMI and waist circumferencethresholds Obesity (Silver Spring) 2011191272ndash127819 Palaniappan LPWong EC Shin JJ FortmannSP Lauderdale DS Asian Americans havegreater prevalence of metabolic syndrome de-spite lower body mass index Int J Obes (Lond)201135393ndash40020 Sumner AE Sen S Ricks M Frempong BASebring NG Kushner H Determining the waistcircumference in African Americans which bestpredicts insulin resistance Obesity (SilverSpring) 200816841ndash846
21 Barbosa PJ Lessa I de Almeida Filho NMagalhatildees LB Araujo J Criteria for centralobesity in a Brazilian population impact onmet-abolic syndrome Arq Bras Cardiol 200687407ndash41422 Medina-Lezama J Pastorius CA Zea-Diaz Het al PREVENCION Investigators Optimal defini-tions for abdominal obesity and the metabolicsyndrome in Andean Hispanics the PREVENCIONstudy Diabetes Care 2010331385ndash138823 Perez M Casas JP Cubillos-Garzon LA et alUsing waist circumference as a screening tool toidentify Colombian subjects at cardiovascularrisk Eur J Cardiovasc Prev Rehabil 200310328ndash33524 Sanchez-Castillo CP Velazquez-Monroy OBerber A Lara-Esqueda A Tapia-Conyer RJames WP Encuesta Nacional de Salud (ENSA)2000 Working Group Anthropometric cutoffpoints for predicting chronic diseases in theMexican National Health Survey 2000 ObesRes 200311442ndash45125 Aschner P Buendıa R Brajkovich I et alDetermination of the cutoff point for waist cir-cumference that establishes the presence of ab-dominal obesity in Latin American men andwomen Diabetes Res Clin Pract 201193243ndash24726 Reaven GM Banting lecture 1988 Role ofinsulin resistance in human disease Diabetes1988371595ndash160727 Kahn R Buse J Ferrannini E SternM Amer-ican Diabetes Association European Associa-tion for the Study of Diabetes The metabolicsyndrome time for a critical appraisal jointstatement from the American Diabetes Associ-ation and the European Association for theStudy of Diabetes Diabetes Care 2005282289ndash230428 Grundy SM Metabolic syndrome pan-demic Arterioscler Thromb Vasc Biol 200828629ndash63629 Bruno G Fornengo P Segre O et al What isthe clinical usefulness of the metabolic syn-drome The Casale Monferrato study J Hyper-tens 2009272403ndash240830 Lemieux I Pascot A Couillard C et al Hy-pertriglyceridemic waist a marker of the ath-erogenic metabolic triad (hyperinsulinemiahyperapolipoprotein B small dense LDL) inmen Circulation 2000102179ndash18431 Rosenzweig JL Ferrannini E Grundy SMet al Endocrine Society Primary preventionof cardiovascular disease and type 2 diabetesin patients at metabolic risk an endocrine soci-ety clinical practice guideline J Clin EndocrinolMetab 2008933671ndash368932 Aguilera CM Olza J Gil A Genetic suscep-tibility to obesity and metabolic syndrome inchildhood Nutr Hosp 201328(Suppl 5)44ndash5533 Benyamin B Soslashrensen TI Schousboe KFenger M Visscher PM Kyvik KO Are therecommon genetic and environmental factors be-hind the endophenotypes associated with themetabolic syndrome Diabetologia 2007501880ndash188834 Dastani Z Hivert MF Timpson N et alNovel loci for adiponectin levels and their influ-ence on type 2 diabetes and metabolic traitsa multi-ethnic meta-analysis of 45891 individu-als PLoS Genet 20128e1002607
2398 Prevalence of Metabolic Syndrome in HispanicsLatinos Diabetes Care Volume 37 August 2014
35 Kristiansson K Perola M Tikkanen E et alGenome-wide screen for metabolic syndromesusceptibility loci reveals strong lipid genecontribution but no evidence for common ge-netic basis for clustering of metabolic syn-drome traits Circ Cardiovasc Genet 20125242ndash24936 Santos DM Katzmarzyk PT Diego VP et alGenotype by energy expenditure interaction
with metabolic syndrome traits the Portuguesehealthy family study PLoS One 20138e8041737 Hotamisligil GS Erbay E Nutrient sensingand inflammation in metabolic diseases NatRev Immunol 20088923ndash93438 Cani PDBibiloni R KnaufC et al Changes in gutmicrobiota control metabolic endotoxemia-inducedinflammation in high-fat diet-induced obesity anddiabetes in mice Diabetes 2008571470ndash1481
39 Turnbaugh PJ Ley RE Mahowald MAMagrini V Mardis ER Gordon JI An obesity-associated gut microbiome with increased ca-pacity for energy harvest Nature 20064441027ndash103140 Vijay-Kumar M Aitken JD Carvalho FAet al Metabolic syndrome and altered gut mi-crobiota in mice lacking Toll-like receptor 5 Sci-ence 2010328228ndash231
carediabetesjournalsorg Heiss and Associates 2399
of Miami (N01-HC65234) Albert Einstein Col-lege of Medicine (N01-HC65235) NorthwesternUniversity (N01-HC65236) and San Diego StateUniversity (N01-HC65237) The following insti-tutes centers or offices contribute to theHCHSSOL through a transfer of funds to theNHLBI National Center on Minority Health andHealth Disparities the National Institute onDeafness and Other Communication Disordersthe National Institute of Dental and CraniofacialResearch the National Institute of Diabetes andDigestive and Kidney Diseases the NationalInstitute of Neurological Disorders and Strokeand the Office of Dietary Supplements
The funding agency had a role in the design andconduct of the study in the collection analysisand interpretation of the data and in the reviewand approval of the manuscriptDuality of Interest No potential conflicts ofinterest relevant to this article were reportedAuthors Contributions GH researched theliterature interpreted the data and organizedand wrote the manuscript MLS NS MMLCC MC RK AG LG LL and LA-Scontributed to the interpretation of the dataand to the writing of the manuscript and wereinvolved in editing during manuscript prepara-tion YT conducted the statistical analysesprovided comments and had oversight of theverification of results GH is the guarantorof this work and as such had full access to allthe data in the study and takes responsibility forthe integrity of the data and the accuracy of thedata analysisPrior Presentation A set of preliminary datafrom this study was presented at the Epidemi-ology and PreventionNutrition Physical Activ-ity and Metabolism 2013 Scientific Sessions ofthe American Heart AssociationAmericanStroke Association New Orleans LA 19ndash22March 2013
References1 Hossain P Kawar B El Nahas M Obesity anddiabetes in the developing worldda growingchallenge N Engl J Med 2007356213ndash2152 BeydounMA Wang Y Gender-ethnic dispar-ity in BMI and waist circumference distributionshifts in US adults Obesity (Silver Spring) 200917169ndash1763 Olshansky SJ Passaro DJ Hershow RC et alA potential decline in life expectancy in theUnited States in the 21st century N Engl JMed 20053521138ndash11454 Ford ES Li C Sattar N Metabolic syndromeand incident diabetes current state of the evi-dence Diabetes Care 2008311898ndash19045 Ballantyne CM Hoogeveen RC McNeill AMet al Metabolic syndrome risk for cardiovascu-lar disease and diabetes in the ARIC study Int JObes (Lond) 200832(Suppl 2)S21ndashS246 Lakka HM Laaksonen DE Lakka TA et al Themetabolic syndrome and total and cardiovascu-lar disease mortality in middle-aged men JAMA20022882709ndash27167 Alberti KG Eckel RH Grundy SM et al In-ternational Diabetes Federation Task Force onEpidemiology and Prevention National HeartLung and Blood Institute American HeartAssociation World Heart Federation Interna-tional Atherosclerosis Society International As-sociation for the Study of Obesity Harmonizing
the metabolic syndrome a joint interim state-ment of the International Diabetes Federationtask force on epidemiology and prevention Na-tional Heart Lung and Blood Institute Ameri-can Heart Association World Heart FederationInternational Atherosclerosis Society and In-ternational Association for the Study of Obe-sity Circulation 20091201640ndash16458 Ford ES Giles WH Dietz WH Prevalence ofthe metabolic syndrome among US adultsfindings from the third National Health and Nu-trition Examination Survey JAMA 2002287356ndash3599 Lavange LM Kalsbeek WD Sorlie PD et alSample design and cohort selection in the His-panic Community Health StudyStudy of Lati-nos Ann Epidemiol 201020642ndash64910 Ford ES Li C Zhao G Prevalence and corre-lates of metabolic syndrome based on a harmo-nious definition among adults in the USJ Diabetes 20102180ndash19311 Daviglus ML Talavera GA Aviles-Santa MLet al Prevalence of major cardiovascular riskfactors and cardiovascular diseases among His-panicLatino individuals of diverse backgroundsin the United States JAMA 20123081775ndash178412 Davidson JA Kannel WB Lopez-Candales Aet al Avoiding the looming LatinoHispanic car-diovascular health crisis a call to action EthnDis 200717568ndash57313 Ervin RB Prevalence of metabolic syn-drome among adults 20 years of age and overby sex age race and ethnicity and body massindex United States 2003-2006 Natl HealthStat Rep 20091ndash714 Derby CA Wildman RP McGinn AP et alCardiovascular risk factor variation within a His-panic cohort SWAN the Study of WomenrsquosHealth Across the Nation Ethn Dis 201020396ndash40215 Allison MA Budoff MJ Wong NDBlumenthal RS Schreiner PJ Criqui MH Prev-alence of and risk factors for subclinical car-diovascular disease in selected US Hispanicethnic groups the Multi-Ethnic Study of Ath-erosclerosis Am J Epidemiol 2008167962ndash96916 Schargrodsky H Hernandez-Hernandez RChampagne BM et al CARMELA Study Investi-gators CARMELA assessment of cardiovascularrisk in seven Latin American cities Am J Med200812158ndash6517 Golden SH Brown A Cauley JA et al Healthdisparities in endocrine disorders biologicalclinical and nonclinical factorsdan EndocrineSociety scientific statement J Clin EndocrinolMetab 201297E1579ndashE163918 Katzmarzyk PT Bray GA Greenway FL et alEthnic-specific BMI and waist circumferencethresholds Obesity (Silver Spring) 2011191272ndash127819 Palaniappan LPWong EC Shin JJ FortmannSP Lauderdale DS Asian Americans havegreater prevalence of metabolic syndrome de-spite lower body mass index Int J Obes (Lond)201135393ndash40020 Sumner AE Sen S Ricks M Frempong BASebring NG Kushner H Determining the waistcircumference in African Americans which bestpredicts insulin resistance Obesity (SilverSpring) 200816841ndash846
21 Barbosa PJ Lessa I de Almeida Filho NMagalhatildees LB Araujo J Criteria for centralobesity in a Brazilian population impact onmet-abolic syndrome Arq Bras Cardiol 200687407ndash41422 Medina-Lezama J Pastorius CA Zea-Diaz Het al PREVENCION Investigators Optimal defini-tions for abdominal obesity and the metabolicsyndrome in Andean Hispanics the PREVENCIONstudy Diabetes Care 2010331385ndash138823 Perez M Casas JP Cubillos-Garzon LA et alUsing waist circumference as a screening tool toidentify Colombian subjects at cardiovascularrisk Eur J Cardiovasc Prev Rehabil 200310328ndash33524 Sanchez-Castillo CP Velazquez-Monroy OBerber A Lara-Esqueda A Tapia-Conyer RJames WP Encuesta Nacional de Salud (ENSA)2000 Working Group Anthropometric cutoffpoints for predicting chronic diseases in theMexican National Health Survey 2000 ObesRes 200311442ndash45125 Aschner P Buendıa R Brajkovich I et alDetermination of the cutoff point for waist cir-cumference that establishes the presence of ab-dominal obesity in Latin American men andwomen Diabetes Res Clin Pract 201193243ndash24726 Reaven GM Banting lecture 1988 Role ofinsulin resistance in human disease Diabetes1988371595ndash160727 Kahn R Buse J Ferrannini E SternM Amer-ican Diabetes Association European Associa-tion for the Study of Diabetes The metabolicsyndrome time for a critical appraisal jointstatement from the American Diabetes Associ-ation and the European Association for theStudy of Diabetes Diabetes Care 2005282289ndash230428 Grundy SM Metabolic syndrome pan-demic Arterioscler Thromb Vasc Biol 200828629ndash63629 Bruno G Fornengo P Segre O et al What isthe clinical usefulness of the metabolic syn-drome The Casale Monferrato study J Hyper-tens 2009272403ndash240830 Lemieux I Pascot A Couillard C et al Hy-pertriglyceridemic waist a marker of the ath-erogenic metabolic triad (hyperinsulinemiahyperapolipoprotein B small dense LDL) inmen Circulation 2000102179ndash18431 Rosenzweig JL Ferrannini E Grundy SMet al Endocrine Society Primary preventionof cardiovascular disease and type 2 diabetesin patients at metabolic risk an endocrine soci-ety clinical practice guideline J Clin EndocrinolMetab 2008933671ndash368932 Aguilera CM Olza J Gil A Genetic suscep-tibility to obesity and metabolic syndrome inchildhood Nutr Hosp 201328(Suppl 5)44ndash5533 Benyamin B Soslashrensen TI Schousboe KFenger M Visscher PM Kyvik KO Are therecommon genetic and environmental factors be-hind the endophenotypes associated with themetabolic syndrome Diabetologia 2007501880ndash188834 Dastani Z Hivert MF Timpson N et alNovel loci for adiponectin levels and their influ-ence on type 2 diabetes and metabolic traitsa multi-ethnic meta-analysis of 45891 individu-als PLoS Genet 20128e1002607
2398 Prevalence of Metabolic Syndrome in HispanicsLatinos Diabetes Care Volume 37 August 2014
35 Kristiansson K Perola M Tikkanen E et alGenome-wide screen for metabolic syndromesusceptibility loci reveals strong lipid genecontribution but no evidence for common ge-netic basis for clustering of metabolic syn-drome traits Circ Cardiovasc Genet 20125242ndash24936 Santos DM Katzmarzyk PT Diego VP et alGenotype by energy expenditure interaction
with metabolic syndrome traits the Portuguesehealthy family study PLoS One 20138e8041737 Hotamisligil GS Erbay E Nutrient sensingand inflammation in metabolic diseases NatRev Immunol 20088923ndash93438 Cani PDBibiloni R KnaufC et al Changes in gutmicrobiota control metabolic endotoxemia-inducedinflammation in high-fat diet-induced obesity anddiabetes in mice Diabetes 2008571470ndash1481
39 Turnbaugh PJ Ley RE Mahowald MAMagrini V Mardis ER Gordon JI An obesity-associated gut microbiome with increased ca-pacity for energy harvest Nature 20064441027ndash103140 Vijay-Kumar M Aitken JD Carvalho FAet al Metabolic syndrome and altered gut mi-crobiota in mice lacking Toll-like receptor 5 Sci-ence 2010328228ndash231
carediabetesjournalsorg Heiss and Associates 2399
35 Kristiansson K Perola M Tikkanen E et alGenome-wide screen for metabolic syndromesusceptibility loci reveals strong lipid genecontribution but no evidence for common ge-netic basis for clustering of metabolic syn-drome traits Circ Cardiovasc Genet 20125242ndash24936 Santos DM Katzmarzyk PT Diego VP et alGenotype by energy expenditure interaction
with metabolic syndrome traits the Portuguesehealthy family study PLoS One 20138e8041737 Hotamisligil GS Erbay E Nutrient sensingand inflammation in metabolic diseases NatRev Immunol 20088923ndash93438 Cani PDBibiloni R KnaufC et al Changes in gutmicrobiota control metabolic endotoxemia-inducedinflammation in high-fat diet-induced obesity anddiabetes in mice Diabetes 2008571470ndash1481
39 Turnbaugh PJ Ley RE Mahowald MAMagrini V Mardis ER Gordon JI An obesity-associated gut microbiome with increased ca-pacity for energy harvest Nature 20064441027ndash103140 Vijay-Kumar M Aitken JD Carvalho FAet al Metabolic syndrome and altered gut mi-crobiota in mice lacking Toll-like receptor 5 Sci-ence 2010328228ndash231
carediabetesjournalsorg Heiss and Associates 2399
