Conceitos de Obesidade

8/12/2019 Conceitos de Obesidade

1/8

The Concept of Normal Weight Obesity

Estefania Olivero sa , Virend K. Somers a , Ondrej Sochor a , b ,Kashish Goe la , Francisco Lopez-Jimene za ,

a Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesotab International Clinical Research Center, St. Anne s University Hospital, Brno, Czech Republic

A R T I C L E I N F O A B S T R A C T

Individuals with normal body weight by body mass index (BMI) and high body fatpercentage show a high degree of metabolic dysregulation. This phenomenon, defined asnormal weight obesity, is associated with a significantly higher risk of developing metabolicsyndrome, cardiometabolic dysfunction and with higher mortality. Recently, we have alsoshown that coronary artery disease patients with normal BMI and central obesity have thehighest mortality risk as compared to other adiposity patterns. Therefore, it is important torecognize these high-risk groups for better adiposity-based risk stratification. There is aneed for an updated definition of obesity based on adiposity, not on body weight.

2014 Elsevier Inc. All rights reserved.

Keywords:Normal weight obesityObesityMetabolically obese normal weightCentral obesityBody fat percentage

The Merriam-Webster dictionary defines obesity as a condi-

tion characterized by the excessive accumulation and storageof fat in the body .1 Obesity is a chronic metabolic disorder characterized by an increase in the number and/or the size of fat cells. Global prevalence of obesity has almost doubledsince 1980 2 and has now become an epidemi c3,4 threatening public health. In 2008, more than 1.4 billion adults in theworld were overweight, from which approximately 200million men and 300 million women were obese .2 Overweightand obesity represent the fifth leading risk for global deaths .2

Formerly thought as a problem of high-income countries,overweight and obesity are becoming more prevalent in low-and middle-income countries.

The American Heart Association and the American Collegeof Cardiology guidelines labeled obesity as a major modifiablecardiovascular disease (CVD) risk factor. Obesity is associatedwith higher rates of insulin resistance, type 2 diabetesmellitus (DM), hypertension (HTN), dyslipidemia, coronaryheart disease (CHD), gallbladder disease, obstructive sleepapnea, non-alcoholic fatty liver disease and some malignan-cies including endometrial, breast, and colon cancer .3,4

Obesity is considered an independent risk factor for CVD 5

and is associated with increased mortality in general healthypopulations .3

Historic perspective of the concept of obesity

Measurement of height and weight was the initial step in theclinical assessment of overweight and obesity. In 1908,Symonds reported the results of a large prospective study of weight and mortality in New Jersey. He registered weight for agiven height and age, and the influence of excess weight onvitality .6 Subsequently, obesity was defined in relation todesirable weight, taking in consideration the actuarial tablesfrom the Metropolitan Life Insurance Company .7 The conceptused was percent of ideal body weight. Later on, the Diet andHealth report questioned the approach of using ideal bodyweigh t8 and suggested that terms like healthy or good weightranges were associated with decreased mortality .9 After-wards, body mass index (BMI) substituted the assessment of obesity, calculated as body weight (in kg) divided by height (in

P R O G R E S S I N C A R D I O V A S C U L A R D I S E A S E S 5 6 ( 2 0 1 4 ) 4 2 6 4 3 3

Statement of Conflict of Interest: see page 432. Address reprint requests to Francisco Lopez-Jimenez, MD, MSc, Division of Cardiovascular Diseases Mayo Clinic. 200 First St SW

Rochester, MN 55905.E-mail address: [email protected] (F. Lopez-Jimenez).

0033-0620/$

see front matter 2014 Elsevier Inc. All rights reserved.http://dx.doi.org/10.1016/j.pcad.2013.10.003

Av a i l a b l e o n l i n e a t w w w. s c i e n c e d i r e c t . c o m

ScienceDirect

w w w. o n l i n e p c d . c o m
http://dx.doi.org/10.1016/j.pcad.2013.10.003http://dx.doi.org/10.1016/j.pcad.2013.10.003http://dx.doi.org/10.1016/j.pcad.2013.10.003mailto:[email protected]://dx.doi.org/10.1016/j.pcad.2013.10.003http://dx.doi.org/10.1016/j.pcad.2013.10.003mailto:[email protected]://dx.doi.org/10.1016/j.pcad.2013.10.003


2/8

meters) squared. Thei ni ti al u se o f t heindex was in 1842 byQuetelet a Belgianmathematician whonoticed that in peoplehe considered to have

a normal frame theweight was propor-tional to the heightsquared .10 In the last3 decades of the 20thcentury, several epi-demiologic studiesused BMI to prove theassociation betweenadiposity and mortali-ty, CVD, DM and manyother obesity-relatedcomorbidities. Withthe help of expertsfrom around the worldwho formed The Inter-national Obesity TaskForce , in 1997 theWorld Health Organi-

zation (WHO) came up with the definition of obesity as aBMI 30 kg/m 2.11,12 The definition also described other degrees of adiposity like overweight and obesity grade 1 and2, although the cutoffs chosen were arbitrary. Fig 1shows the classification of obesity modified by the NationalHeart, Lung and Blood Institute task force, along with

the associated disease risk with increasing BMI .13

Obesity can be also measured using direct and indirectmeasures of fatness other than BMI. The methods to estimatebody fat (BF) include bioelectrical impedance, hydrostaticplethysmography, isotope dilution techniques, dual x-rayabsorptiometry, skinfold method, body impedance measureswith over the counter scales, and air displacementplethysmography .14 Epidemiologic studies have also demon-strated that central fat distribution, measured with waistcircumference (WC), waist-to-hip ratio (WHR) and weight-to-height ratio, is also an important measure of adiposity-related risk .15

Pitfalls of current BF mass measurements

BMI as a measure of BF became popular and widely usedbecause of its simplicity and validation in multiple epidemi-ologic studies. Surprisingly, even though obesity is defined asexcessive adiposity, there is no consensus on how to defineobesity using fat mass calculation or fat percentage, other than the effort by the American Society of Endocrinologistswho defined obesity by BF percent as >35% in women and>25% in men .16 Direct measurement of adipose tissue using methods like water-displacement plethysmography or mag-

netic resonance is too cumbersome to be used in largepopulations or in clinical practice. Newer methods to measure

fat content like air-displacement plethysmography, DEXA or electrical bioimpedance have shown to be valid and notnecessarily expensive.

Although several studies have demonstrated a highcorrelation between BMI and directly-measured BF, thediagnostic performance of BMI is not optimal to identifyleanness or excessive BF. We have tested the accuracy of BMI

for diagnosing obesity in the adult general population using data from 13,601 individuals from the Third National Healthand Nutrition Examination Survey .17 Using bioimpedance tocalculate BF and a BMI >30 kg/m 2 to define obesity, BMI had avery high specificity (97%) but poor sensitivity (42%) to detectobesity 17,18 Therefore, more than half of the individuals withincreased BF percentage may be misclassified by BMI. Inindividuals with BMI of 25 kg/m 2, the index had 86%sensitivity and a specificity of 73%. A meta-analysis of thediagnostic performance of BMI to detect excessive adiposityusing different techniques as the gold standard showedsimilar results .18 A recent study demonstrated a wide rangeof BF % using dual energy x-ray absorptiometry in people withnormal BMI, ranging from 5.6 to 31.2% in men and from 4.6 to51.1% among women .19 The main limitation of BMI is that itcannot differentiate BF from lean mass, and central fromperipheral fat. Therefore, athletes with enhanced bodymuscle mass may be misclassified as obese when using onlyBMI to diagnose obesity, whereas people with low lean massbut high BF content may still have a normal BMI .20

Challenging the simplistic concept of obesity asdefined by BMI

Over the last 30 years, there have been several new conceptschallenging the simplistic concept that obesity can bediagnosed based on weight and height. Numerous studieshave proposed definitions of the obesity subtypes ( Table 1 ).

Firstly, Ruderman et a l21 challenged the notion thatstandard weight height tables were the proper way todetermine high-risk groups for obesity associated disorders.They observed normal weight individuals suffering from type2 DM, premature CHD, HTN and hypertriglyceridemia withassociated hyperinsulinemia. They pointed out that theseabnormalities could not be explained by skinfold thicknessor adipose mass and hypothesized that it was due to larger fat cells. The identified metabolically obese, normal weightindividuals had benefits when they went through programsof energy restriction and weight loss. If patients werechallenged to a 4 12 week period of diet and exercise therewas metabolic improvement .22 Some studies suggested thatthe main issue to explain the metabolic abnormalities inindividuals not particularly overweight was fat distribution.On the basis of these studies, it was proposed a scoring method to identify a metabolically obese normal weightindividual. Depending on the presence of associated diseasesor biochemical abnormalities related to insulin resistance,individuals would be assigned a score to base the diagnosisof metabolically obese normal weight. All of these mentioned

disturbances predispose the individual to suffer from ,23

as well as making them a susceptible population to suffer

Abbreviations and Acronyms

BF = body fat

BMI = body mass index

CHD = coronary heart disease

CVD = cardiovascular disease

DM = diabetes mellitus

HDL = high-density lipoproteincholesterol

HF = heart failure

HOMA = Homeostasis ModelAssessment

HTN = hypertension

LDL = low-density lipoprotein

NWO = normal weight obesity

WC = waist circumferenceWHO = World HealthOrganization

WHR = waist-to-hip ratio

427P R O G R E S S I N C A R D I O V A S C U L A R D I S E A S E S 5 6 ( 2 0 1 4 ) 4 2 6 4 3 3


3/8

from type 2 DM with a three to four-fold time higher riskthan control non-obese individuals .24 Specific reversiblefactors appear to predispose metabolically-obese normal-weight individuals, like decreased aerobic fitness, physicalactivity energy expenditure 25,26 and a lower level of dietaryrestraint .23

Karelis et a l27 and Dvorak et a l25 realized that insulin

sensitivity was related to body composition and that bodycomposition could be a major determinant for the metabolicbehavior of individuals ( Table 2 ). In their review Karelis et a l27

addressed the differences among the metabolically healthyobese, the metabolically obese normal weight, the individualat risk of obesity and the metabolically healthy individual(Table 3 ). Metabolically healthy obese subjects when com-pared with obese insulin resistant adults have a healthier metabolic risk profile and higher disposition index (insulinsensitivity insulin secretion) .28 These findings challenge theconcept that obesity itself produces -cell dysfunction. Mostmetabolically obese normal weight subjects can be identifiedwith risk factors in the familial background, birth weight,adult onset weight gain and central adiposity, physicalactivity status, and the presence of related pathologies .22

In addition to the metabolically obese normal weightphenotype, other subclassifications of obesity have beendescribed, like metabolically normal obesity and NWO.

Normal weight obesity: a distinct phenotype linkedto metabolic dysregulation and inflammation

In 2006, De Lorenzo et a l29 described the association betweennormal weight and high fat content with metabolic abnor-

malities. The term

NWO

described those individuals withnormal body weight and BMI (30%). Despite the fact that obesity is defined as excessivebody adiposity according to the etymology of the word, thereis no consensus about how to define obesity based on BFcontent or %. Some investigators have proposed sex- and age-adjusted cut-off values for NWO. These were defined as thecombination of a normal BMI and increased BF%: 20 39 years,>19% and >32%; 40 59 years, >21% and 33% and 60 79 years,

> 24% and 35% for men and women, respectively .30

A currentchallenge when evaluating BF is that there is no consensusabout thebest cutoff for percent of BF to defineexcessfatness.The different proposed cutoff points of BF vary between 20and 25% for men and 30 and 37% for women .20,31,32

Importantly, metabolically obese normal weight individ-uals likely represent a subset of all NWO people. It is clear thatnot everybody with NWO has the cluster of metabolicabnormalities. However, what has not been clearly deter-mined is what extent of the metabolic dysregulation inmetabolically obese normal weight people could be solelyexplained by increased amounts of total fat, a high BF percentor increased visceral fat.

Relationship between NWO, metabolicdysregulation and inflammation

There is strong evidence linking NWO and metabolicdysregulation. De Lorenzo et a l29 evaluated 74 women andanalyzed anthropometric variables, body composition, resting metabolic rate and biohumoral variables. They found signif-icant differences in high-density lipoprotein (HDL) betweennormal weight obese and pre-obese-obese individuals. Therewere significant correlations among CVD risk indexes, lean of

the right part of the trunk and total cholesterol/HDL (R = 0.69, p < 0.001) and LDL/HDL (R = 0.72, p < 0.001) and lean

Fig 1 Classification of obesity developed by the National Heart, Lung and Blood Institute task force, along with the associateddisease risk with increasing BMI, waist circumference and waist to hip ratio.

428 P R O G R E S S I N C A R D I O V A S C U L A R D I S E A S E S 5 6 ( 2 0 1 4 ) 4 2 6 4 3 3


4/8

and resting metabolic rate (R = 0.44, p = 0.022) in normalweight obese women. Twenty-eight women with high BF(>30%) had significantly lower metabolic rate and oxygenconsumption compared to the 20 women with normal BMIand no excess in BF defined as


5/8

obese group, and the concentrations of interleukin-6 andtumor necrosis factor- were correlated with fat masspercentage in the normal weight obese .33 The cytokinesconcentrations had an intermediate value in the NWOindividuals suggesting that this group was in an earlyinflammatory state .33 Tumor necrosis factor- , interleukin-1and interleukin-6 are related to the adipose mass; conse-quently they are increased in the obese individuals .34 DiRenzo et a l35 studied 60 white Italian women subdivided asfollows: 20 normal-weight individuals (BMI < 25 kg/m 2 ; FM%25 kg/m 2; FM% >30%). Theydemonstrated that NWO women were in early inflammatorystatus, as well as in an oxidative stress related to metabolicdysfunction related to obesity. Reduced glutathione and nitric

oxide metabolites were significantly lower in pre-obese-obese(BMI > 25 kg/m2 ; Fat mass > 30%) and normal weight obesecompared to normal weight individuals .35 Glutathioneshowed a protective role against oxidative and free radical-mediated injury.

There also was a strong association with reduced gluta-thione levels and body weight, BMI and fat mass percentage

(R = 0.45, at least p < 0.05); WC (R = 0.33, p < 0.05); free fatmass (FFM) % (R = 0.45; p < 0.01); interleukin-1 , interleukin-6, interleukin-10, interleukin-15 (R = 0.39, 0.33, 0.36, 0.34, respectively, p < 0.05); and triglycerides (R = 0.416,p < 0.05). Lipid peroxide levels negatively correlated to FFM %(R = 0.413, p < 0.05) and positively correlated to fat masspercentage (R = 0.408), interleukin-15 (R = 0.502), tumor ne-

crosis factor- (R = 0.341), insulin (R = 0.412), total cholesterol(R = 0.4036), low-density lipoprotein cholesterol (R = 0.405),and triglycerides (R = 0.405) [p < 0.05].35

There is a known association between left ventricular dysfunction and heart failure (HF). However, Kosmala et a l36

realized that most of the studies relating HF and leftventricular dysfunction did not assess individuals withnormal BMI but with increased BF content. They designeda study with 168 individuals, from which the normalweight obese subjects demonstrated left ventricle systolicand diastolic dysfunction, increased fibrosis intensity(assessed through procollagen type I carboxyl-terminalpropeptide), impaired insulin sensitivity, and augmentedpro-inflammatory activation in comparison to the individualswith normal BF. Those results were consistent with older studies assessing the link between obesity as measured withBMI, and changes in myocardial performance .37

Marques-Vidal et a l38 conducted a cross-sectional study in3,213 women and 2,912 men and defined normal weightobesity as a BMI


6/8

dependent on the total amount of BF mass rather than on theBF %. On the other hand, adiponectin levels were similar between lean and NWO women .38 Females with NWO hadhigher levels of interleukin-1 , interleukin-1 , andinterleukin-8, but similar values of C-reactive protein,suggesting that the relationship between NWO and inflam-mation is a complex one. Other studies have shown a

polymorphism within interleukin-1 receptor antagonist genesecond intron (A2) associated with an increase in interleukin-1 plasma levels in NWO syndrome .39

Relationship between NWO and metabolicsyndrome(MetS)

There is increased risk for MetS and each one of itscomponents with NWO. Romero-Corral et a l20 demonstratedthat individuals classified as NWO had a prevalence of MetS 4-fold higher than people also with normal BMI but normal BF %.NWO adults also had an increased prevalence of dyslipidemia,DM, hyperglycemia without DM, central obesity and HTN.When divided by sex, women were particularly affected, aswomen in the highest tertile were about 8 times more likely tohave MetS than those in the lowest tertile of BF. This study alsoproved that the prevalence of MetS and of its individualcomponents increased as the BF content increased in menand women ( Figs2 and 3 ). After adjusting forsex, age, and race/ethnicity, body fat was associated with higher odds of having MetS (OR = 1.11, 95% CI 1.09 1.14, for each % point of BF).

A cohort study from Brazil including 1,222 subjectsbetween 23 and 25 years old proved the earlier findings thatNWO was associated with MetS and insulin resistance .40 In

this study, NWO was significantly associated with risk for MetS (OR = 6.83; 95% CI 2.84 16.47) and with the homeostasismodel assessment (HOMA) 2 insulin resistance (OR = 3.81;95% CI 1.57 9.28), low insulin sensitivity (OR = 3.89; 95% CI2.39 6.33) and high insulin secretion (OR = 2.17; 95% CI1.24 3.80). This study also showed significant associationbetween NWO and some elements of the MetS, such as highWC (OR = 8.46; 95% CI 5.09 14.04), low HDL cholesterol (OR =1.65; 95% CI 1.11 2.47) and high triglyceride levels (OR = 1.93;95% CI 1.02 3.64).

Normal weight with central obesity and prognosisin coronary artery disease

Increasing central obesity is linked to higher mortality inadults with or without CHD, even in those with normal BMI .41

Normal weight with central obesity as determined by WC or

WHR in adults with CHD is associated with the highest risk of mortality ,41,42 compared with subjects with normal BMI andno central obesity and with obese patients by BMI regardlessof their central obesity status. Furthermore, the obesityparadox, where people with CHD and obesity by BMI haveshown better prognosis than those with normal weight, doesnot occur when obesity is determined by the fat distribution .41

While higher BMI relates to better prognosis in CHD patients,higher WC or WHR is directly related to higher mortality risk.Those findings may be explained at least in part because BMIhas shown a poor diagnostic accuracy to identify excessiveadiposity in adults with CHD .43 Hence, WC and WHRmeasured in CHD patients will better help to stratify anddevelop therapeutic guidelines for fat loss .41

NWO and mortality.

We have demonstrated that NWO has been associated withincreased CVD and all-cause mortality .20 Women with NWOwere 2.2 times more likely to die from CVDs compared withthose with low BF. When women were classified by tertiles of BF %, the mortality risk increased as the BF %increased. Theincreased mortality risk was independent from HTN, DM anddyslipidemia, suggesting that the increased mortality risk

implicates pathways beyond the traditional obesity-relatedcomorbidities.

Future directions

NWOmaybe present in approximately 30 million Americans .20

The prevalence of NWO varies from 2% to 28% in women andlessthan 3%in men .32,38 We havescarce information regarding the determinants of NWO in the general population. Although

Fig 2 Normal weight obesity: metabolic syndrome criteria by body fat group: men. Fig 3 Normal weight obesity: metabolic syndrome criteria by body fat group: women.

http://localhost/var/www/apps/conversion/tmp/scratch_5/image%20of%20Fig%E0%B3%80http://localhost/var/www/apps/conversion/tmp/scratch_5/image%20of%20Fig%E0%B2%80


7/8

environmental factors are probably implicated in the origin of normal weight central obesity, genetic factors cannot beexcluded. There is a need for epidemiologic studies assessing the prevalence of NWO among different ethnic groups andstudies with genotypic and phenotypic characterization of subjects to elucidate the potential role of genes in the causeand treatment of NWO.

The definition of obesity has become a dynamic conceptthat has evolved for the past 5 decades, as the understanding of adipose tissue continues to evolve too.

However, current evidence suggests that the diagnosis of obesity at the individual level will at some point include somemeasurement of BF content and information on fat distribu-tion. The decision about the diagnostic threshold for fat massor BF % will depend on optimal cutoffs based on epidemio-logic studies with long-term follow-up and information onobesity related comorbidities and mortality.

ConclusionsThediagnosisof obesity hasbeen evolvingover time.Thecurrentdefinition of obesity by weight and height has been challengedwith recent evidence showing that BMI-defined obesity may notaccurately identify all the obesity-related CVD risk. People withnormal BMI and high BF content are at increased risk for metabolic dysregulation, systemic inflammation and mortality.The concept of metabolic obese normal weight overlaps withthe NWO. It is possible that the metabolic dysregulation seen inmetabolic obese normal weight individuals may be all related toincreased body adipositynot detected by BMI. There is a need for studies addressing the complex interaction among fat content,

distribution and activity, and muscle mass content, and their effect on metabolism, CVD risk and survival.

Statement of Conflict of Interest

All authors declare that there are no conflicts of interest.

Acknowledgments

Supported in part by the European Regional DevelopmentFund, project FNUSA-ICRC (Z.1.05/1.1.00/02.0123) and CzechMinistry of Health (NT13434-4/2012).

R E F E R E N C E S

1. Obesity. (Accessed 6/5/2013, 2013, at http://www.merriam-webster.com/dictionary/obesity .).

2. Obesity and overweight. Fact sheet No. 311. March 2013.(Accessed 6/5/2013, 2013, at http://www.who.int/mediacentre/factsheets/fs311/en/ .).

3. Poirier P, Giles TD, Bray GA, et al. Obesity and cardiovas-cular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American HeartAssociation Scientific Statement on Obesity and Heart

Disease from the Obesity Committee of the Council onNutrition, Physical Activity, and Metabolism. Circulation.2006;113:898-918.

4. Pi-Sunyer FX. The obesity epidemic: pathophysiologyand consequences of obesity. Obes Res. 2002;10(Suppl 2):97S 104S.

5. Hubert HB, Feinleib M, McNamara PM, Castelli WP. Obesity asan independent risk factor for cardiovascular disease: a

26-year follow-up of participants in the Framingham HeartStudy. Circulation. 1983;67:968-977.6. Symonds B. The influence of overweight and underweight on

vitality. 1908. Int J Epidemiol. 2010;39:951-957.7. Metropolitan Life Insurance Company. Overweight: its

prevention and significance. Stat Bull Metropol Life Insur Co.1960;41:6.

8. National Research Council. Diet and health, implications for reducing chronic disease risk, National Research Council.Washington, DC: National Academy Press. 1989.

9. Nutrition and your health: dietary guidelines for Americans.US Department of Agriculture and USDepartment of Health and Human Services, Home andGarden Bulletin No. 232. In. 3 ed. Washington, DC.; 1990:273 930.

10. Quetelet LAJ. A Treatise on Man and the Development of HisFaculties. New York: Burt Franklin. 1968.

11. World Health Organization. Physical status: the use andinterpretation of anthropometry. Report of a WHO ExpertCommittee. World Health Organ Tech Rep Ser. 1995;854:1-452.

12. WHO. Obesity: preventing and managing the global epidemic.Report of a WHO Consultation. WHO Technical Report Series894. Geneva: World Health Organization. 2000.

13. NHLBI Obesity Education Initiative Expert Panel on theIdentification, Evaluation, and Treatment of Overweightand Obesity in Adults. Clinical Guidelines on theIdentification, Evaluation, and Treatment of Overweightand Obesity in Adults The Evidence Report. NationalInstitutes of Health. Obes Res. 1998;6(Suppl 2):51S 209S.

14. Cornier MA, Despres JP, Davis N, et al. Assessing adiposity: ascientific statement from the American Heart Association.Circulation. 2011;124:1996-2019.

15. Mathieu P, Poirier P, Pibarot P, Lemieux I, Despres JP. Visceralobesity: the link among inflammation, hypertension, andcardiovascular disease. Hypertension. 2009;53:577-584.

16. AACE/ACE Obesity Task Force. AACE/ACE position statementon the prevention, diagnosis, and treatment of obesity.(1998 revision). Endocr Pract. 1998;4:297-349.

17. Romero-Corral A, Somers VK, Sierra-Johnson J, et al. Accuracyof body mass index in diagnosing obesity in the adult generalpopulation. Int J Obes. 2008;32:959-966.

18. Okorodudu DO, Jumean MF, Montori VM, et al. Diagnosticperformance of body mass index to identify obesity as definedby body adiposity: a systematic review and meta-analysis. Int J Obes. 2010;34:791-799.

19. Kennedy AP, Shea JL, Sun G. Comparison of the classificationof obesity by BMI vs. dual-energy X-ray absorptiometry inthe Newfoundland population. Obesity (Silver Spring). 2009;17:2094-2099.

20. Romero-Corral A, Somers VK, Sierra-Johnson J, et al.Normal weight obesity: a risk factor for cardiometabolicdysregulation and cardiovascular mortality. Eur Heart J.2010;31:737-746.

21. Ruderman NB, Schneider SH, Berchtold P. The metabolically-obese, normal-weight individual. Am J Clin Nutr. 1981;34:1617-1621.

22. Ruderman N, Chisholm D, Pi-Sunyer X, Schneider S. Themetabolically obese, normal-weight individual revisited.Diabetes. 1998;47:699-713.

432 P R O G R E S S I N C A R D I O V A S C U L A R D I S E A S E S 5 6 ( 2 0 1 4 ) 4 2 6 4 3 3
http://www.merriam-webster.com/dictionary/obesityhttp://www.merriam-webster.com/dictionary/obesityhttp://www.who.int/mediacentre/factsheets/fs311/en/http://www.who.int/mediacentre/factsheets/fs311/en/http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0005http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0005http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0005http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0005http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0005http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0005http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0005http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0005http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0010http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0010http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0010http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0010http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0010http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0010http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0010http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0015http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0015http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0015http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0015http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0015http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0015http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0020http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0020http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0020http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0020http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0175http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0175http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0175http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0175http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0025http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0025http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0025http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0180http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0180http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0185http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0185http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0185http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0185http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0185http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0190http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0190http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0190http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0195http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0195http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0195http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0195http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0195http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0195http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0195http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0195http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0195http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0195http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0195http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0195http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0030http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0030http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0030http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0030http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0035http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0035http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0035http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0035http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0035http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0040http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0040http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0040http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0040http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0040http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0200http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0200http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0200http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0200http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0200http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0045http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0045http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0045http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0045http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0045http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0045http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0050http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0050http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0050http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0050http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0050http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0050http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0055http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0055http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0055http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0055http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0055http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0060http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0060http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0060http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0060http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0060http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0060http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0060http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0060http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0060http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0065http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0065http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0065http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0065http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0065http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0065http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0065http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0060http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0060http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0060http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0055http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0055http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0055http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0055http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0050http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0050http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0050http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0050http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0045http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0045http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0045http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0045http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0200http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0200http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0200http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0040http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0040http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0040http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0035http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0035http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0035http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0030http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0030http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0030http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0195http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0195http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0195http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0195http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0195http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0195http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0190http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0190http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0190http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0185http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0185http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0185http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0180http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0180http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0025http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0025http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0025http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0175http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0175http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0175http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0020http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0020http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0015http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0015http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0015http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0015http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0010http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0010http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0010http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0005http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0005http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0005http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0005http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0005http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0005http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0005http://www.who.int/mediacentre/factsheets/fs311/en/http://www.who.int/mediacentre/factsheets/fs311/en/http://www.merriam-webster.com/dictionary/obesityhttp://www.merriam-webster.com/dictionary/obesity


8/8

23. Conus F, Allison DB, Rabasa-Lhoret R, et al. Metabolicand behavioral characteristics of metabolically obese butnormal-weight women. J Clin Endocrinol Metab. 2004;89:5013-020.

24. Meigs JB, Wilson PW, Fox CS, et al. Body mass index,metabolic syndrome, and risk of type 2 diabetes or cardiovascular disease. J Clin Endocrinol Metab. 2006;91:2906-2912.

25. Dvorak RV, DeNino WF, Ades PA, Poehlman ET. Phenotypiccharacteristics associated with insulin resistance in meta-bolically obese but normal-weight young women. Diabetes.1999;48:2210-2214.

26. Ruderman NB, Berchtold P, Schneider S. Obesity-associateddisorders in normal-weight individuals: some speculations.Int J Obes. 1982;6(Suppl 1):151-157.

27. Karelis AD, St-Pierre DH, Conus F, Rabasa-Lhoret R, PoehlmanET. Metabolic and body composition factors in subgroups of obesity: what do we know? J Clin Endocrinol Metab. 2004;89:2569-2575.

28. Succurro E, Marini MA, Frontoni S, et al. Insulin secretion inmetabolically obese, but normal weight, and in metabolicallyhealthy but obese individuals. Obesity (Silver Spring). 2008;16:1881-1886.

29. De Lorenzo A, Martinoli R, Vaia F, Di Renzo L. Normal weightobese (NWO) women: an evaluation of a candidate newsyndrome. Nutr Metab Cardiovasc Dis. 2006;16:513-523.

30. Gallagher D, Heymsfield SB, Heo M, Jebb SA, Murgatroyd PR,Sakamoto Y. Healthy percentage body fat ranges: an approachfor developing guidelines based on body mass index. Am J ClinNutr. 2000;72:694-701.

31. Romero-Corral A, Montori VM, Somers VK, et al. Associationof bodyweight with total mortality and with cardiovascular events in coronary artery disease: a systematic review of cohort studies. Lancet. 2006;368:666-678.

32. Marques-Vidal P, Pecoud A, Hayoz D, et al. Prevalence of normal weight obesity in Switzerland: effect of variousdefinitions. Eur J Nutr. 2008;47:251-257.

33. De Lorenzo A, Del Gobbo V, Premrov MG, Bigioni M, Galvano F,Di Renzo L. Normal-weight obese syndrome: earlyinflammation? Am J Clin Nutr. 2007;85:40-45.

34. Hauner H. Secretory factors from human adipose tissue andtheir functional role. Proc Nutr Soc. 2005;64:163-169.

35. Di Renzo L, Galvano F, Orlandi C, et al. Oxidative stress innormal-weight obese syndrome. Obesity (Silver Spring).2010;18:2125-2130.

36. Kosmala W, Jedrzejuk D, Derzhko R, Przewlocka-Kosmala M,Mysiak A, Bednarek-Tupikowska G. Left ventricular functionimpairment in patients with normal-weight obesity:contribution of abdominal fat deposition, profibrotic state,reduced insulin sensitivity, and proinflammatory activation.

Circ Cardiovasc Imaging. 2012;5:349-356.37. Wong CY, O'Moore-Sullivan T, Leano R, Byrne N, Beller E,Marwick TH. Alterations of left ventricular myocardialcharacteristics associated with obesity. Circulation. 2004;110:3081-3087.

38. Marques-Vidal P, Pecoud A, Hayoz D, et al. Normal weightobesity: relationship with lipids, glycaemic status, liver enzymes and inflammation. Nutr Metab Cardiovasc Dis.2010;20:669-675.

39. Di Renzo L, Bigioni M, Del Gobbo V, et al. Interleukin-1 (IL-1)receptor antagonist gene polymorphism in normal weightobese syndrome: relationship to body composition and IL-1alpha and beta plasma levels. Pharmacol Res. 2007;55:131-138.

40. Madeira FB, Silva AA, Veloso HF, et al. Normal weight obesityis associated with metabolic syndrome and insulin resistancein young adults from a middle-income country. PLoS One.2013;8:e60673.

41. Coutinho T, Goel K, Correa de Sa D, et al. Central obesity andsurvival in subjects with coronary artery disease: a systematicreview of the literature and collaborative analysis withindividual subject data. J Am Coll Cardiol. 2011;57:1877-1886.

42. Coutinho T, Goel K, Correa de Sa D, et al. Combining bodymass index with measures of central obesity in theassessment of mortality in subjects with coronary disease:role of normal weight central obesity . J Am Coll Cardiol.2013;61:553-560.

43. Romero-Corral A, Somers VK, Sierra-Johnson J, et al. Diag-nostic performance of body mass index to detect obesity inpatients with coronary artery disease. Eur Heart J. 2007;28:

2087-2093.44. Kim JY, Han SH, Yang BM. Implication of high-body-fat

percentage on cardiometabolic risk in middle-aged, healthy,normal-weight adults. Obesity (Silver Spring). 2013;21(8):1571-1577.

http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0070http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0070http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0070http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0070http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0070http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0070http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0075http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0075http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0075http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0075http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0075http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0075http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0080http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0080http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0080http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0080http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0080http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0085http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0085http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0085http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0085http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0090http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0090http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0090http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0090http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0090http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0090http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0095http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0095http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0095http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0095http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0095http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0095http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0100http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0100http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0100http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0100http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0100http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0105http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0105http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0105http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0105http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0105http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0105http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0110http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0110http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0110http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0110http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0110http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0110http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0115http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0115http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0115http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0115http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0115http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0120http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0120http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0120http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0120http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0120http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0125http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0125http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0125http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0125http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0130http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0130http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0130http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0130http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0135http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0135http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0135http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0135http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0135http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0135http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0135http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0140http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0140http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0140http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0140http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0140http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0140http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0145http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0145http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0145http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0145http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0145http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0150http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0150http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0150http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0150http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0150http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0150http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0155http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0155http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0155http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0155http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0155http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0160http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0160http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0160http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0160http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0160http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0160http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0165http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0165http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0165http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0165http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0165http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0165http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0165http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0165http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0165http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0165http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0170http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0170http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0170http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0170http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0170http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0170http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0205http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0205http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0205http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0205http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0205http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0205http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0205http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0205http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0205http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0205http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0170http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0170http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0170http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0170http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0165http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0165http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0165http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0165http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0165http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0160http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0160http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0160http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0160http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0155http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0155http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0155http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0155http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0150http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0150http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0150http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0150http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0145http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0145http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0145http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0145http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0140http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0140http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0140http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0140http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0135http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0135http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0135http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0135http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0135http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0135http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0130http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0130http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0130http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0125http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0125http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0120http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0120http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0120http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0115http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0115http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0115http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0110http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0110http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0110http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0110http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0105http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0105http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0105http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0105http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0100http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0100http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0100http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0095http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0095http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0095http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0095http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0090http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0090http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0090http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0090http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0085http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0085http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0085http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0080http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0080http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0080http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0080http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0075http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0075http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0075http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0075http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0070http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0070http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0070http://refhub.elsevier.com/S0033-0620(13)00176-X/rf0070

Documents

Conceitos de Obesidade