REPRINTED FROM WWW.ENDOTEXT.ORG Chapter 1 Definitions and Classifi ation of O!

esit"
#n$elo Del Pari$i% M.D.% Senior Director, Medical Lead Academic Medicine, Specialty Care Business Unit, Pfizer Inc.

&pdated 1 '(ne )*1*

Definition and et"+olo$"

O esity is a state of e!cess adipose tissue mass. "#is condition usually translates into e!cessi$e ody %ei&#t. On t#e one #and o esity can de$elop e$en in t#e a sence of e!cessi$e ody %ei&#t, %#ereas on t#e ot#er #and a person 'e&, a ody uilder( can de$elop remar)a le o$er%ei&#t %it#out e!cessi$e ody fatness. Interestin&ly, t#e %ord *o esity+ 'from t#e Latin obesitas), used today in a purely descripti$e %ay, in its etimolo&y, points to t#e most common e#a$ioral condition leadin& to o esity, ie o$ereatin&. In fact, obesitas is t#e condition of t#e obesus 'ie, plump(, %ord t#at, in turn, is composed of ob 'ie, o$er( and esus, ie t#e past participle of edere 'ie, to eat(.

Dia$nosis
,i$en t#at an e!cess of ody fat is t#e definin& $aria le of o esity, a proper dia&nosis of o esity %ould re-uire t#e assessment of ody fatness. "#is can e performed indirectly in many different %ays. Most accurately no%adays y usin& t#e dual ener&y !.ray a sorptiometry 'D/0A(, %#ic# -uantifies total and re&ional ody fat y assessin& t#e differential attenuation of t%o !.ray eams %it# different intensities 'ie, ener&y le$els( as t#ey tra$el t#rou&# t#e ody of an indi$idual. 1o%e$er, t#is met#odolo&y re-uires a special mac#ine %#ic# in$ol$es a minimal e!posure to !.rays. 2or practical reasons, t#e measurement of ody %ei&#t #as een adopted as a $alid pro!y for ody fat and it is used to calculate t#e so called ody mass inde! 'BMI(, %#ic# is defined as %ei&#t3#ei&#t4 ')&3m4( '2i&.5(.

Fi$(re. 1 6 2ormulas for t#e calculation of BMI

"#e identification of t#e cut.off for o esity %as ased on lar&e scale mor idity data, %#ic# pointed to a BMI 789 )&3m4 as t#e o$erall t#res#old for an increase in mor idity ris). Conse-uently, o esity is dia&nosed in indi$iduals %it# a BMI :89 )&3m4. In c#ildren, t#e dia&nosis is ased not on a solute parameters, ut on t#e BMI percentiles of #istorical normal &roups of t#e same a&e and &ender, e&, t#e ones reported in t#e CDC &ro%t# c#arts '2i&s.4.8(. If t#e measured BMI is : ;<t# percentile, o esity is dia&nosed '5(. A more se$ere o esity is sta&ed at a BMI : ;=t# percentile.

Fi$(re ) 6 BMI for a&e> percentiles 6 Boys, 4.49 years of a&e

Fi$(re , 6 BMI for a&e> percentiles 6 ,irls, 4.49 years of a&e

In t#eir simplicity, %#ic# fa$ored t#eir %ide use, t#ese dia&nostic criteria are $ery appro!imate. Besides t#e nosolo&ical inconsistence %it# t#e definition of o esity as

e!cess ody fat, a ody %ei&#t ased uni$ersal criterion lac)s in sensiti$ity, for e!ample, to t#e &ender and et#nic related differences in relati$e ody fatness. In fact, for t#e same BMI, %omen are, on a$era&e, fatter t#an men, and Asians are, on a$era&e, fatter t#an Caucasians. As a result, in ?apan, o esity is dia&nosed at a BMI :4< )&3m4 '4(, in C#ina at a BMI :4@ )&3m4 '8(, %#ile for Caucasians, a BMI in t#e inter$al 4<.89 )&3m4 is dia&nosed as o$er%ei&#t. Dia&nostic t#res#olds for o esity ased on percent ody fat #a$e also een proposed> A 4<B for men and A 88B for %omen 'C(, ut t#ere is no uniform consensus on t#ese $alues 'also ecause tec#ni-ue.dependent( and no &eneral access to t#e &old standard tec#ni-ue for t#e assessment of ody fat, ie D/0A, as discussed a o$e.

Classifi ation
O esity can e classified in se$eral different %ays> for e!ample, y BMI inter$als and related a&&re&ate ris) of mortality, y anatomic p#enotypes or y etiolo&ic criteria. Accordin& to t#e Dorld 1ealt# Or&anization 'D1O(, o esity is classified as class I for a BMI et%een 89 and 8C.; )&3m4, class II for a BMI et%een 8< and 8;.; )&3m4, and class III for a BMI : C9 )&3m4 '<(. In turn, class I o esity is associated %it# '#ence, la eled as( a *moderate ris)+, class II %it# a *#i&# ris)+, and class III %it# a *$ery #i&# ris)+ of mortality 'C(. "#e most common anatomical c#aracterization refers to a pre$alently $isceral or a pre$alently su cutaneous deposition of fat. "#e ratio of %aist circumference to #ip circumference 'D1E( #as ser$ed t#e purpose of definin& t#e de&ree of central 'ie $isceral( $s. perip#eral 'ie su cutaneous( o esity. It is )no%n t#at $isceral adiposity is a maFor ris) factor for meta olic complications of o esity, %#ile su cutaneous fat seems to e muc# more eni&n, and in some cases e$en protecti$e a&ainst t#e de$elopment of meta olic complications 'G(. 2rom an etiolo&ic standpoint o esity can e fundamentally classified as primary or secondary. O esity, in fact, can e iatro&enic, ie secondary to p#armacolo&ic treatments, includin& some antipsyc#otics, some antidepressants, some antiepileptics, and steroids. An o esity p#enotype is also c#aracteristic of some diseases or conditions, includin& polycystic o$ary syndrome, Cus#in&Hs syndrome, #ypot#yroidism, #ypot#alamic defects, and &ro%t# #ormone deficiency. On t#e ot#er #and, as a primary disorder, o esity still #as an elusi$e etiolo&y. D#ile its pat#o&enesis can e e!pressed in relati$ely simple t#ermodynamic terms, ie t#e e!cess of ody fat stora&e as a result of a

c#ronic positi$e ener&y alance 'ie, surplus of ener&y inta)e $s. e!penditure(, t#e identification of t#e primary causes of t#e c#ronic ener&y im alance remains c#allen&in&, %#ile t#e meta olic, psyc#olo&ical, and e#a$ioral p#enotypes leadin& to *&arden $ariety+ o esity are still contro$ersial. In fact, e!cessi$e ener&y inta)e 'or #yperp#a&ia( is considered an o $ious p#enotype of o esity '=(. 1o%e$er, lin)in& #yperp#a&ia to actual %ei&#t &ain #as pro$ed e!ceptionally difficult '@I;(, most li)ely ecause it is in#erently c#allen&in& to measure ener&y inta)e in free.li$in& indi$iduals. Ot#er aspects of food inta)e and t#eir relations#ip to o esity, suc# as diet composition '59.5G(, ener&y density of food '5=.5;(, rate of meal consumption '49(, taste preferences '45.4C(, eatin& e#a$ioral style '4<I4G(, and su .p#enotypes '4=.85(, #a$e also een e!plored %it# some%#at contradictory results. Jot surprisin&ly, t#e molecular iolo&y of o esity is also only partially understood. "#is is li)ely due to t#e #etero&eneity of *&arden $ariety+ o esity and t#e fact t#at it is caused, li)e ot#er comple! diseases, not y a sin&le &enetic mutation ut y multiple allelic defects, %#ic# determine suscepti ility to en$ironmental factors '84(. Indi$iduals %#o carry only one or some of t#ese alleles may still not de$elop t#e disease, ecause t#ey eit#er lac) anot#er allele '&ene6&ene interaction( or are not e!posed to t#e precipitatin& en$ironment '&ene6en$ironment interaction(. 2urt#ermore, t#ere is contro$ersial e$idence for a direct association et%een &enotypes and lifestyle '88( or anatomical '8C( p#enotypes of o esity.

Epide+iolo$"% +ortalit"
O esity affects a lar&e proportion of t#e population, %orld%ide. 1o%e$er, estimates of its pre$alence are not a$aila le for all countries, and t#e a$aila le data are not uniformly accurate or compara le '8<I8G(. In t#e United States, t#e Jational 1ealt# and Jutrition /!amination Sur$ey 'J1AJ/S( in t#e last <9 years #as pro$ided a continuous monitorin& of pre$alence and incidence of o esity in a nationally representati$e sample of indi$iduals. "#ese data s#o% t#at t#e pre$alence of o esity amon& adults 'a&e : 49 years( started to increase mar)edly after 5;@9. In 499=.9@ 't#e most recent set of data a$aila le( it reac#ed an a&e.adFusted pre$alence of 88.@B o$erall, correspondent to 84.4B in men and 8<.<B in %omen '8G( '2i&.C(. 1o%e$er, o$er t#e last decade '5;;;. 499@(, no si&nificant c#an&es #a$e een o ser$ed in t#e pre$alence of adult o esity amon& %omen and only an o$erall linear trend for men #as een o ser$ed, indicatin& t#at t#e pre$alence of o esity amon& adults is not &ro%in& at t#e same rate recorded for

t#e pre$ious t%o decades '8G(. "#e #i&#est pre$alence is currently o ser$ed amon& non.1ispanic Blac)s 'CC.5B, 8=.8B for men, C;.GB or %omen(, follo%ed y 1ispanics '8@.=B, 8C.8B, C8.9B(, and non.1ispanic D#ites '84.CB, 85.;B, 88.9B( '8G( '2i&.<(. By se$erity, &rade 4 o esity #as an o$erall pre$alence of 5C.8B '59.=B amon& menI 5=.@B amon& %omen(, %#ile &rade 8 reac#es a pre$alence of <.=B 'C.4B amon& men, =.4B amon& %omen(. "#e racial distri ution follo%s t#e same pattern as for o$erall o esity, e!cept for &rade 8 %#ic# is as pre$alent amon& 1ispanics '<.<B( as amon& non.1ispanic D#ites '<.4B( '8G(.

Fi$(re - . Pre$alence of o esity 'BMI :89 )&3m4( amon& U.S. adults in 5;@< and 499@ 'Source> CDC Be#a$ioral Eis) 2actor Sur$eillance System(

Fi$(re . . Pre$alence 'B( of o esity 'BMI :89 )&3m4( amon& U.S. adults y

Eace3/t#nicity, 499G.499@ 'Source> CDC Be#a$ioral Eis) 2actor Sur$eillance System(

Amon& c#ildren and adolescents 'a&e K 49 years(, ased on t#e 499=.9@ J1AJ/S, o esity reac#ed a pre$alence of ;.<B in oys and &irls 9.4 years of a&e '59.9B for oys, ;.9B for &irls(, %#ile t#e pre$alence for c#ildren 4.5; years of a&e %as 5G.;B o$erall '5=.@B for oys, 5<.;B for &irls('8=(. Alt#ou&# t#e pre$alence of o esity #as tripled amon& sc#ool.a&e c#ildren and adolescents since 5;@9'8=(, no si&nificant trend %as o ser$ed in t#e last decade e!amined '5;;;.499@(, e!cept at t#e #i&#est BMI cut point 'BMI : ;=t# percentile( amon& G.5; year.old oys '8=(. "#e pre$alence of o esity y race.et#nicity in c#ildren is #i&#est amon& 1ispanics> 54.<B for 9.4 year.old c#ildren and 49.;B for 4.5; year.old c#ildren, follo%ed y non.1ispanic Blac)s> 59.8B for 9.4 year.old c#ildren and 49.9B for 4.5; year.old c#ildren, and non.1ispanic D#ites> @.=B for 9.4 year.old c#ildren and 5<.8B for 4.5; year.old c#ildren '8=(. Interestin&ly, o esity is also emer&in& as a pandemic in pets '2i&.G(, particularly in do&s, %it# an estimated 49B to C9B of domestic do&s ein& o ese '%ei&#t : 55<B ideal %ei&#t( '8@(. "#e importance of t#is &ro%in& pro lem is underscored y t#e a$aila ility of a specific dru& 'dirlotapide, Slentrol L( recently appro$ed y t#e 2DA for treatment of canine o esity.

Fi$(re / 6 Una Familia MA 2amilyN 'a paintin& y 2. Botero(

Alt#ou&# mor idity and mortality ris)s are &enerally #i&#er for o ese people, t#e relations#ip %it# BMI, in t#e o esity ran&e, is not necessarily linear or uniform for disease 'e& cancer( '8;IC9( su types, &ender 'C5(, or race3et#nic &roups 'C5(. In some cases, data do not support an increased ris) in o ese people '8;IC9(. 2or #ip fractures, t#e ris) is reported to e lo%er for a BMI around 89 )&3m4 '8;(, %#ile in o ese patients under&oin& #emodialysis 'C4(, or %it# #eart failure and perip#eral artery disease 'C8(, #ealt# outcomes seem to e etter t#an for patients %it# normal %ei&#t. "#ese o ser$ations #a$e &enerated t#e so called *o esity sur$i$al parado!+ 'C4(. Accordin& to some aut#ors, t#is parado! is e!plained y t#e fact t#at patients lose %ei&#t as t#e underlyin& illness pro&resses 'CC(I anot#er confounder could e t#at more a&&ressi$e treatment is administered to o ese patients compared to normal %ei&#t patients 'C<(. On t#e ot#er #and, t#is parado! #as recently een su&&ested as a potential e!planation for t%o %ell esta lis#ed epidemiolo&ical o ser$ations> '5( t#e U.s#aped 'ie, conca$e( relations#ip et%een BMI and mortality rate, suc# t#at people %it# intermediate BMI '4<. 89 )&3m4( tend to li$e lon&er t#an people %it# lo%er or #i&#er BMIsI and '4( t#e nadirs of t#ese cur$es tend to increase monotonically %it# a&e 'CG(.

0istori al referen es
Alt#ou&# it #as e!ploded into pandemic proportions in t#e last t%o decades, o esity #as een )no%n since pre#istoric times, as epitomized y t#e famous Oenus of Dillendorf '2i&. =(. "#e first to point out #ealt# ris)s associated %it# o esity and t#e pat#o&enetic role of e!cessi$e food inta)e %as, #o%e$er, 1ippocrates, t#e &reat ancient ,ree) p#ysician 'C=( around C99 BC. A fe% centuries later 'AD5G9( ,alen, a &reat ancient Eoman p#ysician, documented t#e first )no%n successful %ei&#t loss pro&ram y increasin& p#ysical e!ercise and controllin& food inta)e 'C=(. "#rou&# t#e Sc#ola Medica Salernitana and ot#er medie$al medical sc#ools in /urope t#is )no%led&e %as passed on to a &ro%in& num er of practitioners and &ained solid scientific ases y accruin& clinical o ser$ations and post.mortem e!aminations. In fact, t#e first &reat pat#olo&ist, Mor&a&ni, re$ealed in 5=G< t#e e!istence of different fat depots and discussed t#e pat#olo&ical rele$ance of t#e intra.a dominal fat and its correlated p#enotypes 'C=(. "#e researc# on t#e pat#op#ysiolo&y and p#enotypization of o esity %as t#en launc#ed, and 4C< years later remains a fertile field of scientific disco$eries and contro$ersies.

Fi$(re 1 . Oenus of Dillendorf. c.4C,999.44,999 BC/ 'Jatur#istorisc#es Museum, Oienna(

Referen es
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2le&al PM, O&den CL, Dei E, Puczmars)i EL, ?o#nson CL. Pre$alence of o$er%ei&#t in US c#ildren> comparison of US &ro%t# c#arts from t#e Centers for Disease Control and Pre$ention %it# ot#er reference $alues for ody mass inde!. Am ? Clin Jutr 4995I =8'G(>59@G.;8.

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Panaza%a M, Qos#ii)e J, Osa)a ", Jum a Q, Rimmet P, Inoue S. Criteria and classification of o esity in ?apan and Asia.Oceania. Asia Pac ? Clin Jutr 4994I 55 Suppl @>S=84.S=8=.

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Bei.2an R. Predicti$e $alues of ody mass inde! and %aist circumference for ris) factors of certain related diseases in C#inese adults> study on optimal cut.off points of ody mass inde! and %aist circumference in C#inese adults. Asia Pac ? Clin Jutr 4994I 55 Suppl @>SG@<.SG;8.

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Bray ,A. Contemporary Dia&nosis and Mana&ement of O esity. 5;;@. Je%to%n 'PA(, 1and oo)s in 1ealt# Care Co. Eef "ype> ,eneric

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?ensen MD. Eole of ody fat distri ution and t#e meta olic complications of o esity. ? Clin /ndocrinol Meta 499@I ;8'55 Suppl 5(>S<=.SG8.

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Delpari&i A, Pannacciulli J, Le DJ, "ataranni PA. In pursuit of neural ris) factors for %ei&#t &ain in #umans. Jeuro iol A&in& 499<I 4G Suppl 5><9.<.

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Stun)ard A?, Ber)o%itz EI, Stallin&s OA, Sc#oeller DA. /ner&y inta)e, not ener&y output, is a determinant of ody size in infants. Am ? Clin Jutr 5;;;I G;'8(><4C. 89.

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"ataranni PA, 1arper I", Snit)er S, DelPari&i A., Oozaro$a B, Bunt ? et al. Body %ei&#t &ain in free.li$in& Pima Indians> effect of ener&y inta)e $s e!penditure. Int ? O es Eelat Meta Disord 4998I 4='54(>5<=@.@8.

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Astrup A. Macronutrient alances and o esity> t#e role of diet and p#ysical acti$ity. Pu lic 1ealt# Jutr 5;;;I 4'8A(>8C5.=.

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Astrup A, "ou ro S, Ea en A, S)o$ AE. "#e role of lo%.fat diets and fat su stitutes in ody %ei&#t mana&ement> %#at #a$e %e learned from clinical studiesS ? Am Diet Assoc 5;;=I ;='= Suppl(>S@4.S@=.

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Ba#adori B, Qazdani.Biu)i B, Prippl P, Brat# 1, Uitz /, Dasc#er "C. Lo%.fat, #i&#.car o#ydrate 'lo%.&lycaemic inde!( diet induces %ei&#t loss and preser$es lean ody mass in o ese #ealt#y su Fects> results of a 4C.%ee) study. Dia etes O es Meta 499<I ='8(>4;9.8.

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2riedman MI. 2uel partitionin& and food inta)e. Am ? Clin Jutr 5;;@I G='8 Suppl(><58S.@S.

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1ill ?O, Astrup A. D#at diets s#ould %e e recommendin& for o esityS O es Ee$ 4998I C'4(>==.@.

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Prentice AM. Manipulation of dietary fat and ener&y density and su se-uent effects on su strate flu! and food inta)e. Am ? Clin Jutr 5;;@I G='8 Suppl(><8<S. C5S.

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Dillett DC, Lei el EL. Dietary fat is not a maFor determinant of ody fat. Am ? Med 4994I 558 Suppl ;B>C=S.<;S.

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Bell /A, Eolls B?. /ner&y density of foods affects ener&y inta)e across multiple le$els of fat content in lean and o ese %omen. Am ? Clin Jutr 4995I =8'G(>5959. @.

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Dre%no%s)i A. "#e role of ener&y density. Lipids 4998I 8@'4(>59;.5<. Duncan P1, Bacon ?A, Deinsier EL. "#e effects of #i&# and lo% ener&y density diets on satiety, ener&y inta)e, and eatin& time of o ese and nono ese su Fects. Am ? Clin Jutr 5;@8I 8='<(>=G8.=.

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Meyer ?/, Pudel O. /!perimental studies on food.inta)e in o ese and normal %ei&#t su Fects. ? Psyc#osom Ees 5;=4I 5G'C(>89<.@.

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Coolin& ?, Blundell ?/. 1i&#.fat and lo%.fat p#enotypes> #a itual eatin& of #i&#. and lo%.fat foods not related to taste preference for fat. /ur ? Clin Jutr 4995I <<'55(>595G.45.

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Dre%no%s)i A. "aste preferences and food inta)e. Annu Ee$ Jutr 5;;=I 5=>48=. <8.

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Mela D?, Sacc#etti DA. Sensory preferences for fats> relations#ips %it# diet and ody composition. Am ? Clin Jutr 5;;5I <8'C(>;9@.5<.

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Sal e AD, Delpari&i A, Pratley E/, Dre%no%s)i A, "ataranni PA. "aste preferences and ody %ei&#t c#an&es in an o esity.prone population. Am ? Clin Jutr 499CI =;'8(>8=4.@.

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Berteus 21, "or&erson ?S, SFostrom L, Lindroos AP. Snac)in& fre-uency in relation to ener&y inta)e and food c#oices in o ese men and %omen compared to a reference population. Int ? O es Eelat Meta Disord 499<.

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Pes)i.Ea#)onen A, Paprio ?, Eissanen A, Oir))unen M, Eose E?. Brea)fast s)ippin& and #ealt#.compromisin& e#a$iors in adolescents and adults. /ur ? Clin Jutr 4998I <='=(>@C4.<8.

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Delpari&i A, C#en P, Sal e AD, Eeiman /M, "ataranni PA. Sensory e!perience of food and o esity> a positron emission tomo&rap#y study of t#e rain re&ions affected y tastin& a li-uid meal after a prolon&ed fast. Jeuroima&e 499<I 4C'4(>C8G.C8.

'4@(

1ays JP, Bat#alon ,P, McCrory MA, Eou enoff E, Lipman E, Eo erts SB. /atin& e#a$ior correlates of adult %ei&#t &ain and o esity in #ealt#y %omen a&ed <<.G< y. Am ? Clin Jutr 4994I =<'8(>C=G.@8.

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La%son O?, Dilliamson DA, C#ampa&ne CM, DeLany ?P, Broo)s /E, 1o%at PM et al. "#e association of ody %ei&#t, dietary inta)e, and ener&y e!penditure %it# dietary restraint and disin#i ition. O es Ees 5;;<I 8'4(>5<8.G5.

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Lindroos AP, Lissner L, Mat#iassen M/, Parlsson ?, Sulli$an M, Ben&tsson C et al. Dietary inta)e in relation to restrained eatin&, disin#i ition, and #un&er in o ese and nono ese S%edis# %omen. O es Ees 5;;=I <'8(>5=<.@4.

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Pro$enc#er O, Drapeau O, "rem lay A, Despres ?P, Lemieu! S. /atin& e#a$iors and inde!es of ody composition in men and %omen from t#e Tue ec family study. O es Ees 4998I 55'G(>=@8.;4.

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Pomp D, Mo#l)e PL. O esity &enes> so close and yet so far.. ? Biol 499@I =';(>8G.

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1olzapfel C, ,rallert 1, 1ut# C, Da#l S, 2isc#er B, Dorin& A et al. ,enes and lifestyle factors in o esity> results from 54 CG4 su Fects from MOJICA3POEA. Int ? O es 'Lond( 4959.

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Lenz M, Eic#ter ", Mu#l#auser I. "#e mor idity and mortality associated %it# o$er%ei&#t and o esity in adult#ood> a systematic re$ie%. Dtsc# Arzte l Int 499;I 59G'C9(>GC5.@.

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Sc#midt DS, Sala#udeen AP. O esity.sur$i$al parado!.still a contro$ersyS Semin Dial 499=I 49'G(>C@G.;4.

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