newsandv

iewsfea
ture

Th
edoub
lepu
zzl
eofd
iab
ete
s
Ja
red D
iamond

Whyisthe prevalence oftype 2 d

iabetes me
l
litus now exp
lodingin mos
t
populat
ions, bu
tno tin Eu
ropeans?The geneticand evolut
ionaryconsequences
of geograph
icaldif
ferencesinfood histo
ry may providethe answe
r.

T
yp e2d iab ete sm ellituse xactsahu ge to l
l P
im as
,a susu a
llyassum ed;th eyarem e
rely p
l ayaqu antita
ti velym ino rro l e(w ithou t
in mon e yandhum ansu fferin g.F o
r theextremee xamp le
s.In stead,theab erra
- denyin g thee xis
ten ceo fsu ch factors3,13)
.
in stan ce, ita ccoun tsfo r mo reth an1 00 t
iond em andingexplanationisEu rope
. ●T hep r evalenceo fd iab etesamon gH isp an ic
bi
lliondo llarso fh ealth c areco st
sannu al
l yin A
sane v
olut
ion a
r ybiolo g
ist,Ihavelon g Am eric ansv arie
sa cco rdin g toth eirp ropo r-
10
theUn itedS t ates,o r1 5%o fco stsdu etoa l
l be
enpu zz
ledb ythesed iffe
ren ce
s.Inth is tiono fN ativeAm e r
ic ang en et
ican c e
st ry .
diseas escomb in ed. Th enumb ero fc a ses ar
tic
leIsh a
llsugges
tah ypo thesis
forwh yw e ●M an ysp ecif
icg en etic su s
c eptibili
ty facto rs
worldw id ei se stim at eda t1 5 0m illion .Bu t ar
eno tsee
in gnear
lyasmu cho fanexplosion haveb een identif
i ed11,12.B e caus eth eh igh es
t
this isam inimumnumb erb ecau se,fo re ach amon gEu ropeansasamon go the
rpopu l
a- mutationr atesforan yhum ang en ea reon ly
diagno sedc a se,th er ei sthou ghttob eon e t
ions.Thee vid
en c
ec om esini
tiall
yfrom food around1 0 5p erg en era t
ion , thee xp ectation
und ia gno s edc as einF irstW or
ldcoun t ries h
istory
,andt es
tsofitm ayc om ef
romm edi- isth aton l yd e
l eteriou sg en esw i
thp re va
-
1
ande i gh tinth eTh ird W orld .D espit ei t
s c
in e
,m ed
i c
alhisto
ryandmo l
e cul
arbiology
. lenc esb elow1 05cou ldb esu stainedw ith in
othe rn am eo fadu lt-on s e
td iab etes,th e apopu l a
tionb yr ecu rr ent mu t
a t
ion sa lon e
.
diseas eisb ecom in gmo recommon inyoun g Gene
ticsandl
ifes
tyle Thea ctu alin c
id en ceo ft yp e2d i abetes isup
peop le2,3.A t
i tsp r es
en t rat eofincr ease,w ithin Gen et
icsTh ehighp r
e valen ceo ftyp e2d ia- to5 0, 000t im esh igh er.Andth eh i ghp rev a
-
af ewd ec ad esi tw illb eon eo fth ewo rld’s betesinan ylargepopu lationpo sesa fu rther lenc eo fth edisea sein m an ylar ge,an ci ent
,
common es td ise asesand b iggest pub lic- evolutionaryqu estion. Wh y i
s thed iseas eso wel
l-m ixedpopu lation sru l esou te xplan a-
healthp rob lem s2,4,w ithane s
tim ated m in i
- common ,wh enitshou ldd isapp eara stho se tions in term softh efound e reffecto rg en eti
c
mumo fh alf-a-b il
lionc as es5.Th ise xp lo sion gen et
ical
lysu sceptibletoi tar eremo vedb y dri
ft.Th ese,respe ctively,ar einstan ceswh ere
inp r eval enc ei so ccu r r
in ge sp eciallyinth e natu r
als elect
ion?(R ead ers who an sw e
r, therew ason lyav er ylim it edin it
i a
lg en eti
c
Third W orld,a tabou t5 0%p erd ecad e;and “B ecausei
tk i
llsonl yold erindi v
idu alswho se variability
,o rwh e rer andomp ro cessessu ch
becau seth eep id em i cis ju s
tb eginn in g in th e child-bearingo r child -r e
a r
in gy earsa re ass electiv ee xt
in ctionop erated,andth ey
world ’stwo mo stpopu lou scoun tries,Ind i a behind th em” w i
llf ind th is ob je c
tion tend toa ffe c
ton ly sm allpopu la
tion s.H en ce
,
andCh in a,b y th ey ea r2 0 10mo reth anh alfo f answ eredb elow.)Th ed is e
a s
ec e
rt a
in lyh as theh i ghp reval
en ceso ft yp e2d iab etes,li k
e
2
,3,5 11
,12
thewo rld’sd i ab eticsw il
lb eA s
ian s . ag eneticcompon en t ,a sise v
id en tfrom thep rev a
len ceo fsi ckle- c
ellan a em ia inc er
-
Th erea retwo m ainfo rmso fd iab et es the fol
lowin g. taing roup s
,mu stb esu st a
in edb ysom ecom -
mel
litu s,and th ep rin cip alch aracteristic sa re ●T hereisacon cord an ceind i
a gno siso f pens a
tin gad vanta geth ato ffs e
tsth eob viou s
outlin edinBo x1 .Bu tth isisth es to ryo f nearly1 00%fo r mono zy gotictw ins( tho se morbid i
t yandmo rtality (inth eca seof s
i ckle-
typ e2 ,no ton lyb e cau sei ti s mu ch mo re thatd eve
lopf romth es am ef er
til
i zede gg
, cel
ld ise ase,thecomp en s a
tin gad vanta gei sa
commonandr isin gs te eplyinp re valen c e
, andsoh aveid ent
ic a
lg en eticcon stitution s
), certainr esistance tom al ar
i a).
butb ecau s eth atr isei sdoub l ypu zzlin g. buton ly2 0%fo rd izygo t
i ctw ins.Th e latter Life
s tyleInadd itiontoth a
tg eneticcom -
Noton lywou ld th edis eas es eem tob eh igh ly figurei scomp arabletoth atfo rnon -twin pon ent,t ype2d iab et
e sa lso in vol ves
disad v ant ageou sint erm so fn atur als el ec- sibl
in gs
,su ggest
in gth atfa c
to rsinth eu terus en v
ironm entalandl ifestyler iskf ac
to rs—
tion ,bu t som ehum anpopu lat
ion sa remu ch
mor ea f
f ect edth ano th ers.
Th eg eo g
r aph i calv a r
i at
ion sa reshown in B
ox1T
hed
iv
ers
i
tyo
fd
iab
ete
sme
l
li
tus
Fig
.1(o ve rl
e af )
.Th e low estpre valen c es,o f Theterm‘diabe
tesm e
l
li
tus
’c o
versaw ideva
rietyofc o
ndi
tionstha
tarelinkedonl
yb ys haredsym pt
om s
practi callyz ero ,a reinru ralTh ird W o r
ld ar
isi
ng f
romh ighleve
lsofbloods ugar
.Thatdive
rsi
tym a
yb ecrude
lypart
iti
oned2
,3
,11
,12
intotype2
area s
, wh e reasth eh igh est,3 7– 50% ,a re (adu
lt-on
s e
t)and t
he l
ess-comm on ty
pe1 (
juv e
nil
e-o n
set
).Therespec
tivepreva
len cesam ongdiabet
icsin
amon gN au ru Is
l and erso fth etrop ic a
lP acif- theU n
ite
dS tate
sa re90–95%a nd5 –10%.Bothdiseasescent
reo ntheh o
rm on
ei n
s u
lin,w h
ichisrespons
ibl
e
6
,7 8
ic ,P im aInd ian sin A r
izon a andu rb an form ed
ia
ting t
heu pta
keb yc e
ll
so fgluc
osefrom theblood
.
Wani gelap eop l ein P apu aN ew Gu in e a9. Type1d iabe
tes(ins
ul
in-d epe
n den
tdiabe
tesm e
l
litus
)isana u
toimm unediseaseinw h
ichautoan
tibod
ies
Mosto fth e wo rld’ sb ro ad g eo g raph i cal dest
roythep anc
reat
ic-
isle
tc el
lsthatsyn
thes
iz e
i n
sul
i n
.P a
t
i e
ntsareth
in,produceli
ttleorn oi
ns u
l
i n
,and
group in gso fp eop lein c
lud epopu lation so f arepronetok e
tos
is,ap a
rt
icularm etab
ol
icim ba
lance.Theycarrycer
ta
i ngenetypes— theHLAalle
lesDR3,
bothv erylowandv e ryh ighp re valen c e— DR4orb o
t h— tha
te ncodep ar
ti
c u
larcompo nen
tsof th
eimm unes y
stem.T yp
e2d ia be
t es
(non-insu
l
in-
forin st an ce,M apu ch eInd iansv ersu sA ri
- dependen
tdi abe
tesm el
l
itus
) invo
lvesal
teredinsu
lins e
cre
tionandinsu
linres
istance
.P a
tien
tsareo f
ten
zon aP im a Ind i an s,andru ralN ewGu in e ans obeseandar enotsubje
cttok eto
sis
.T heydoproduce i
nsul
inb u
tb ec
om einsul
in-
resistant— thatis
,u nab
le
versu sth eu rb an W an igela.P opu l ation s torespondeffec
tive
lytoi
t.
und er goin gin cr eases in th ein c
id en ceo ft yp e Dis
tin
g u
ishingthetwoform scanb ecompl
i c
ated,how e
v e
r
,b ecaus
e the
reise a
rly-onsettype2a nd
2d i ab etesin clud eno ton lyA si anInd ian s late
-onse
t type1.Type2d iabete
s isi
tse
lfve
r yhete
r ogene
o u
s,bothgeneti
cal
lya ndin t
h eassoc
iated
andCh in ese,bu ta l soJ ap anese,A bo rigin a
l patho
log
icala n
dp hys
iolo
gicalsym p
tom s
.T h
ed isea
s ear
isesfr
oma tleast60ident
if
i edg ene
t
icdisorde
rs,
Austr alian s,H isp ani cAm ericansandA fro - un
itedonlyby th
ec omm onfeatureofhighbl
o od
- g
lucoseleve
lsd u
etoins u
l
inresis
ta nce
.T hi
sh e
terogene
it
y
Am e rican s2,4,10.Acon spi cuou se x cep t
ioni s re
i n
forc
esth eevol
ut
i o
naryp uzz
le
:g enestha
tp red
isposethebearertotype2diabetesm us
treal
lyc on
vey
theab sen ceo fan ycomp arablee xp lo sion, somea dvan
ta ge
,b ecau
seth eyhavee v
iden
tlybeenp rese
rvedindependent
lym anyt
im esbynatura
ls e
lec
tion
.
orv er y-hi gh -p rev alen c epopu lat
ion ,amon g The‘th
ri
ft
yg e n
e’hypothes
is,accordingtowhichsuchg enesal
loweff
icientf
oodu t
i
lizati
o nint
im esofpl
enty
,
peop leo f Eu rop eanan cestry
. Thu s,th e inprepara
tionforfamine
,pr ov
idesap oss
ib
lee xpl
an a
tion
. J.D
.
puz zlin gab err ation sa reno tN au ru an sand
NATURE|VOL4
23|5
JUNE2
003|www
.na
tur
e.com
/na
tur
e © 2003Na
turePub
lish
ingG
roup 599
newsandv
iewsfea
ture
esp eci a
ll y
,h ighc alo riein tak eand lowe xer- phenom enon —anep idem ico fag en etic (ob e
sityandth es ed en taryl ifestylea rea s
2,11
,12,
14
cise .F o re xamp le: disea se6,7.Ep id em icso fin f ectiou sd ise ases commona se ve r),bu tp r esum ablyb ec ause
●D is eas ep rev alenc eis5– 10t im esh i gh er in wax wh ent ran sm iss
iono fth ein fe ct
iou s tho s
ewhoa reg enetic al
ly mo stsu s ceptible
ob esep eop leth an in tho seo fno rm alw eigh t. agen tin c rea ses;th eyth en w an e wh enth e haved ied.I fth isin t erpret ationi sco rrect,
●T h em etabo licabno rm alitiesands ymp - numb ero f su sc eptiblepo ten tialvi ct
im sf alls
, thenN aurup ro vid esth emo s tr apid inst ance
tom so fd i ab etesc ano f
tenb er e vers edb y du ebo thtoa cqu iredimmun ityo fth esu r
- known tom eo fn atur alselection inahum an
dietin gande xer ci
se. vivo rsandtod if
f erenti a
l mo r
t al
it yo ftho s
e popul at
ion —ano ccu rren ceo fd etect able
●T hes ymp tom sd eclin eo rd isapp ea rin whoa reg en etic al
ly sus cep t
ib le.Anep id em ic popul at
ion -wid es e
le ctionw i thinl e ssth an
popu lation sund ers tarv at
ioncond ition s— ofag en eticd ise a
s ew a xesb ecau seo far ise in 40y ears
.
as,fo r in stanc e,th eyd id inF ren chd iab etics en vironm en t a
lr is kf actor s
,andth enw an e
s Thec a seo fN aurua lsoi llu strates wh y,
und erth efoodr ation in gimpo seddu rin g whenth enumb ero fsu scep tiblepo ten tial ear
lierinth isa rticle,Id ism i ssedth eu su a
l
3
th e1 8 7 0–7 1sie geo fP aris. victim sf a
lls(bu ton lyb ec aus eo fth ep ref er
- object
ionth att yp e2d iab e
t es lack ss e
l ective
●P r ev a
l enc eo fd iab et e
sin crea sesw i thin enti ald eath so ftho s e whoa reg en etic all
y imp actb e c
au sei tsuppo s edl ya ffectsp eople
1
,15
abou ttwod ec ades inpopu l ation sth at mor esu s cep tibl e)
. only wh enth e
i rr eprodu cti vey earsa re
ha veadop t edah igh -c a
lo r
i e
,low -e xer cise Th et rad ition allifest yleo fN au ru an sw as behindth em .Inf ac
t,a lthou ghth ed is ease
li
f est y
l ea s ar esulto f em igr ation :fo r based on a g ricultu re andf ishin g
, and app earsm a
inl yaft e
ra ge5 0inEu rop ean s,in
in stan c e
,wh enY em en iteJ ew sw erea irlifted in vol vedf requ entep isod eso fs tar vation Nauru ans and o the r non -Eu rop e ansi t
toI sr ael,and wh enth erew asabu r sto f bec au seo fd rou ghtsandth ei sland ’spoo r af
fe c
tsp eop leo fr ep rodu cti vea geinth eir
Jap an e seem i grationtoth e Un itedS tat es. soil.E arly Eu rop eanv i
sito rsn ever th eless twen t
i e
sandth irt
i es
,e sp eci al
lyp regn ant
Oth ere xamp lesa reg roup so fem igr an t not edth atN au ru an sw erep lump ,andth a
t wom en,who s ef etusesandn ewbo rnb ab i
e s
AsianInd ian sinF iji
,M au r
itius,S in gapo re, the yadm i redb ig,f atp eop leandpu tg irlson arealsoa tin cre asedr isk.F orin stan ce,in
Tan zan ia,th eUn i
t edS tatesandB rit ain3,4,16, adi et to fatten th emandsom ake th emmo r
e Japantod ay
, mo r ech i
ld rensu fferf romt ype
ando fem i gran t Ch in esein H on gK on g
, attra ctive.In1 90 6i tw a sd isco ver edth a
t 2th ant yp e1d iab etes,d esp it eth el att e
r’s
Mau ritiu s
,S in gapo reandT a
iw an2,3,17. mosto fN au ru con sistso fh i gh -qu alit y popul arn am eo f ju ven i
le -on se
td iab etes.
● P r ev alen ces imil ar
l yr isesr apid l yina pho sph atero ckth atcou ldb eu sedfo rf e r
- Moreov er
,int r adition alhum anso cieties,
popu lationth atr em ain sinth es am eg eo - til
iz er,andin1 92 2th em in in gcomp an y unl
i ke mod ernF irstW or
ldso ciet
i es
,noo ld
graph ic a
la reabu tin wh ichc alo riein ta ke extr actin gth ero ckb egantop ayro yaltie sto person i
st ruly‘po st-rep rodu cti ve
’and s elec-
in cre asesande x
er cised ecreas es
.E xamp les thei s
l and ers.A sar esulto fth i sn eww e alth, tive
lyun impo rt ant,b ecau seg randp aren t
s
in clud eth eN au ruI sl and ers,A rizon aP im a aver ag esu garcon sump tionb yN au ru ans contributec ru ciallyto thefood supp l y
, so c
i a
l
Ind ian s,wh iteA u
s tralian s
,u rb anA bo ri gin al rea ch eda pound p erd ayb y1 92 7
,and sta
tu sandsu rvi va
lo fth eirch ild renand
18
Au stralian s,u rb anb l ac kA frican sin C ap e labou r ersw er e impo rtedb e cau seN au ru ans grand chi
ld ren .
Town1, u rban S amo an s
, Ch in es e,A sian dis
li kedwo r kin ga sm in e rs
.
Ind ian sand Jap ane se. Du rin gth eS econd W orld W arth eisland Th
rif
tygenes
●I nJ ap an,g r aphsa g a
in sttim eo fth ein ci- waso ccup iedb yJ ap an esem ili
t ar yfo r ces, Th el eadin ge v olution aryth eo ryfo rth e
den c eo ft ype2d i ab etesando fe conom ic whoimpo s edfo rc edl abou r,r edu cedfood pos s
ibleb en e f
i tso fg enesp redispo s
in gto
ind ic ato rsa rep a
r al
l e
l —downtod et a
il so f ration stoh alf- a-poundo fpump kinp erd ay, typ e2d iab et esi sJ am esN eel
’s‘thrif
t yg en e
’
yea r-to -yea rw i gg
l es.Th at’sb ecau s ep eop le and th end epo rtedmo sto fth epopu la t
ion to hypo the s
is3,14,19,20. N eel po s
tul a
ted th e
eat mo re,andsor is kd evelop in gd iab etic Tru k,wh ereh alfo fth emd iedo fs tar vation . existenc eo f m etabo lical
lyth ri
ftyg en es
:
3
symp tom s
,wh enth eyh avemo remon ey . Whenth esu r v
i v orsr e
tu rn ed ,th e yr eg a
in ed th esep erm itmo r eefficientfoodu tilization,
●A sIl earn edwh il es er v
in gonth eAn im al thei rpho sph atero yalt
i es
,andr esum ede at- fatd epo si
tionandr apid w eightg aina t
Re gul at
ion Comm itteeo fth eLo sAn gel es in gsu garando th ersto re-bou ght food .Th ey occ as
ion altim eso ffoodabund ance,th ereb y
Zoo ,th e reisnowad iab etesep id em icamon g abandon eda gricu ltur ea lmo stcomp l etely
, makin gth eg en e -b ea rerbetterableto su rvive
cap tiv e popu l at
ion s o f m an y p rim ate bec am es ed en t a
r y
,andc am etor ely on asub sequ en tf am in e.E x
amp leso fth r
ifty
sp ecie swho sezoo l
if estyleapp ro x
im a
t es th e moto rv eh icl esto tr avela round th eir2 0 -km2 gen es wou ldin clud etho ser esultin gin
high -c alorie,low -e xercisel i
f es
t y
l eo fu rb an island .F ollow in gind ep end en cein1 96 8,p er highl e ve
lso fin sulin o ro fl eptin ( a
hum an sin theF ir
stW orld.Itw illb ein s
t ru c- cap itapho sph atero yaltiesro setoA $ 37, 5 0
0 hormon erel e as edb yf atcellsthatr egu lates
tivetos eewh ethero rno tou rp rim ater el a- (U S $ 22, 50 0)annu ally,m a kin gN au ru an s app eti
t e)
,o rinh air-tr
i ggeredinsulin releas e
.
tivessh areg en escon ferrin gsu scep tibilit yto amon gth e wo r
ld ’sr ich estp eop l e.T od a
y Suchg en es wou ldb ead vantageou sund er
diab ete sw ithu s. the ya r eth emo s
tob es eandh a veth eh igh est th econd ition so funp redictab
l yaltern ating
Allina l
l,th eb asiso ft yp e2d i ab etesc an bloodp r essu reo fa l
lp eop lesinth eP acific
; feast andf am in eth atch aract
eriz edth e
besumm arizeda sfo llow s3:i t“ isal ifest yle thei ra v era ge bod y w ei ghti sh alfa s trad i
tion al hum an l ifes
tyle, bu t th ey
diso rd erw ithth eh igh e
stp reval en ces e en mucha g aina sth ato fA u
st ralian so fEu ro - wou ldl eadtoob e
sityandd iabetesinth e
in popu la t
ion sth ath avea h ei gh ten ed peano r
i gin. mod ern wo rld wh enth es am eind ividu als
gen eti csu scep tibi
lit y;en vironm en talf ac- Althou ghco lon ialEu rop eanph ysician s stope xerc
i sin g,b e g
info ra g
in gfo rfood
to rsa sso ciated w ithl ife
st y
l eunm a skth e onN au rukn ewhow tor eco gni zet yp e2d i a
- onl yinsup erm arkets,andcon sum eth ree
dise ase ”
. betes,andd i agno sed i
t th ereinnon -N au ru an high -ca
lo riem e alsd ayin,d ayou t
.F ollow in g
labou r ers,th e firstc ase inN auru an sw asno t Arthu rK oes tle r
,Z imm e
tr efer
s to th e
Nau
ru not edun ti
l1 9 2 5
.Th es econdw asr eco rd ed spr eado fth is li festyletoth eTh i
rd W orlda s
3,
4
Nauruisar emo teis
landinth ePaci
fi
cth at in1 9 34.A fter1 95 4
,how e ver,th ep re va
l en ce “co ca-colon iz at ion ” .
wascolonizedb ytheM icrones
iansinp re- ofth ed ise asero ses teepl yand itb e cam eth e Soa ccustom eda rew einth eFirstW orld
h
istorict
im es
.I tw asann exedbyG erm any common e s
tc au seo fnon -ac c
id en tald e ath. tor egularm e al sth a tw ef indi th a rdto
in1 888,occup i
edb yA u
stral
iain1 91
4and On e-th irdo fa llN au ru an so ve rth ea geo f2 0, im ag
in eth eflu ctu a
tin gfooda vailabil
it yth a
t
eventual
lyachievedind ependence
in1 968.I
t two -third so ftho seo vera g e5 5,and7 0%o f wasfo rm er
l yth eno rmandr em ain ssoin
isthewo r
ld’s
sm a
ll
estrepublic
,butita
lsoh a
s tho s ef ewwhosu r vivetoth ea geo f7 0,a re som ep artso f th ewo r
ld .Ioftenen coun tered
alessw e
lcom edist
inction.Th ei
slandisthe diab etics.W ith in th ep astd e cad e,p re valen ce su ch f luctu a tion s du r
in g m yf ieldwo rk
s
iteo fagriml yins
tructiveepidemicofd ia
- ofth ed ise aseh asb eguntof al
l,no tb ecau se amon gN ewGu in ea moun taineersstillsub -
bete
s,wh i
ch i
llustr
atesar ar
elydocum ented ofm itig ationo fen vironm en talri skf ac to r
s sis
tin gb yfarm in gandhun tin g
.F ore xamp le
,
600 © 2003Na
turePub
lish
ingG
roup NATURE|VOL4
23|5
JUNE2
003|www
.na
tur
e.com
/na
tur
e
 newsandv
iewsfea
ture
som ey e arsa go,ina m emo r abl ein cid ent,I wer e th en s et ap artf rom mo sto the r
hiredado zenm en toc arr yhe av yequ ipm ent PacificI sland er sb yth e
i re x trem es t arv ation
Populat
ion Reg
ion Percen
tage
al
ld ayo veras teept railuptoa moun tain grouping preva
lence
and mo rtali
t y du rin gth eS econd W orld
camp site. W ea rriv edju s
tb efo resun set, War,l e avin gth e popu lation p resum ab ly
Eu
ropeans B
ri
tain 2
exp ectin gto m e e
tano th erg roupo fpo rt ers Germany 2
ev enmo reen ri ch ed ind iab et essu scep tib i
lity
withfood ,andin s teadfoundth atth e yh ad Austra
l
ia(1981
) 2 gen es. A fter th e w ar, th eirn ew -found
nota r r
iv edb ecau seo fa m isund erst and in g
. Austra
l
ia(2002
) 8 wealth,sup er abund an tfoodandd im in ish ed
Fac edw ithhun gr y,e xh au s
t ed m enandno Uni
tedS ta
tes 8 needfo rph y
si cala ctivit yl edt oe x cep tion al
food ,Ie xp ectedtob el yn ch ed.In stead,m y Na
tive Ch
i
le Mapuche 1
ob esi
t y
.
carrie rsju stl au gh edands aid,“ O rait
,i American
s USHispan
ic 17 Th eP im asL i keo th e rN ativ e Am eric ans,
sam t
in gn a
tin g,yum isli pn atin g,en apyum i USPima 50 Arizon aP im a Ind ian sw ere fo rm erlyp e asan t
kai kaitum o ra”( “OK ,it’snob i gd eal
,w e’ll farm ersandhun te r– gath e rers whoh ada
Pac
if
ic Nau
ru(1952
) 0
sleeponemp tys tom ach ston i gh tandw ait Is
lande
rs Nau
ru(2002
) 41
ph ysicallyv igo rou sl ifest yleand w e rea t
ti
lltomo rrowtoe at” )
.Con v ersel y
,ono th er period icr isko fs tar vation .Th e
ire xtrabou t
occ as
ion swh enp i gsw eres lau gh teredfo ra New Rura
l 0 ofn a
tu rals e
le ctionpo ssibl yc am edu r
in gth e
fea st
,th eN ew Gu in ean s wou ldcon sum e Gu
inean
s Urban 37 lat en in e
t een thc en tu r y
, wh en Eu rop ean
prod igiou samoun tso ffood .Th isan ecdo te Abo
rig
ina
l T
rad
it
ional 0
imm igr antsd ive rtedth eh eadw a
t erso fth e
il
lu strates an a ccommod ation to th e Aus
tra
l
ians Wes
tern
ized 23 riv er
son wh ichth eP im asd ep end edfo r
pendu lumo ffe astandf am in eth atw asv ery irri ga
tion w a ter. Th er esu l
t w asc rop
nec essaryint im e s wh enth atp endu lum M
idd
leEa
st Yemen,trad
itiona
l 4 failur es,w ide sp re ads t arv ationand th eli kel
y
YemeniteJewsinIs rae
l 13
swun go ftenbu ti rre gul ar
ly —as itu ation Lebanon, weste
rni
zed 14
en richm en to fth esu rvi vin gpopu l at
ionin
8,22
th atw as mu ch mo ret ypic a
lo fou re volu - th rif
t yg en es .
tion ar yh istor yth anth est ateo fp l ent yto B
lack Rura
lTanzania 1 Eu rop eEu rop e an sa reun iqu eamon gth e
whi chw ea rea c custom ed. A
fr
icans UrbanSouthAfr
ica 8 mod e
rnwo r
ld ’spopu l ation s inth er elati ve-
Uni
tedStates 13
Twol in eso fhum ane v
id en c eandtwo lylow p rev alen c eo ft yp e2d i ab etes
.
anim al mod e
lssuppo r tth ep lau sibilityo f Ch
ine
se Ru
ralCh
ina 0 Althou gh p r ev alen c eo f th ed is eas ei s
Neel’sth r
ift yg en eh ypo th es
is.N on -di ab et
i c U
rbanSingapore 9 in crea sin g
,i ti ss t
illlow e rth aninan ynon -
Nau ru ansandA rizon aP im aInd i ansh a ve U
rbanTaiwan 12 Eu rop eanpopu l at
ion m at ch edfo r life style,
U
rban Maur
it
ius 13
po stprand iall evelso fp l a
sm ain su lin( in ev enthou gh Eu rop e an s —in Eu rop e
respon setoano r a
lg lu coselo ad )th ata re A
sianInd
ians Ru
ralInd
ia 0 itself,andth rou ghou tth e wo rld —a r
e
14
tripletho s eo f Eu rop ean s . And g iv en U
rbanTanzania 11 th erich estandb e st-fedp eop l e
in th ewo r
ld,
amp lefood ,d iab etes -p ron epopu l a
tion so f U
rbanInd
ia 12 andth eo rigin ato r so fth eW estern li
f est y
l e
.
U
rbanSingapore 17
PacificI sland ers,N at
i ve Am e rican s and U
rban Maur
it
ius 17
AsF ig.1show s,e vencomp a red w ithth e
Abo rigin al Au stralian s do e xh ibit mo re U
rbanFi
ji 22 Eu rop ean popu lation w i th th eh i gh est
prop en sitytoob e s
it yth anEu rop ean s:first pre valen ce(wh iteAu str alian s,8% ),a lmo st
th eyg ain w eigh t
,th enth e yd e velopd ia- al
lo th er m ajo r popu l ation g roup in gs
bete s
.A s to thean im a
le xamp les,l abo rato ry Figure1A ge-standard izedp re valenceo ft ype2 (N at
iv e Am eric an s, P acific I sl and ers
,
ratsc arr y
in gg en esp redispo sin gth emto diabet esm el
litus.Amon gth em ainf eaturesa re Abo rigin al Au strali an s
,E astA s
i an s and
typ e2d i ab etesandob esitysu rvi ves tar va- the lowp re valenceamon gg roup so fEu rop e an Sou thA sianso fth eInd iansub con tin ent)
tionb etterth andono rm alr ats, il
lu stratin g origin,e sp ecial
lytho ser em ain inginEu rop e;the in clud e popu lation sw ith mu ch h i gh e
r
th ead van ta g
eo fth es eg en esund e ro cca- highp revalen ceamon gP im aInd ian sandu rb an pre valen ceso f1 5– 5 0% .
16
sion al cond i
tion so ff am in e . Andth e NewGu ine ans,andamon gN auru anstod ay
;and Thisun iqu elylowo c cu rren ceo ft yp e2
Isra e
lis andr at,wh ich isad ap tedtoad e sert theh i gh erp reva
len ce inu rb ano rw esternized diab etes amon g Eu rop ean si s cu riou s.
en vironm en tw ithf r equ ents car c
itieso f group s,comp aredw ithth ei
rru ralo rtrad i
tion a
l Se verale xp e
r tsinth es tud yo fth ed is ease
food ,d e velop sh ighl e ve
lso fl ep t
inand coun te rparts.B ecau set ype2p revalen ceina ha ve su g gested to m e in form all y th at
in sulin,andin sulinr esistan ce,ob esi
t yand givenpopu lationin cre asesw itha ge,itwou ldb e perh ap sEu rop ean st r adition al
l yh adl ittle
diab etes
,wh enm aint a
in edin th el abo rato ry mis
le adin gtocomp arer awv alu esofp rev a
len ce expo su r etof am in e,soth atth e y wou ld
ona‘w esterni zedr atd i e
t’w ithabund an t betw eentwopopu lation sth atd i
fferinth eir ha veund ergon el ittles el ectionfo rath rifty
food .Bu ttho ses ymp tom sr ev ersewh eni ts aged ist r
ibu tion;th er awv alu eswou ldb e geno t yp e.Bu tth is isno tth ec as e —th e reis
21
food isre s
tri c
t ed . exp ectedtod ifferm e relyasar esulto fth e abund antdo cum en tationo ff am in esth a
t
di
ffe ren tag edistr
ibu tion s,ev en i
fp r eva
l ence s ha vec au sedw id esp re adand sever emo rtality
23– 2
7
Na
tura
lse
lec
tion atag iv ena gew ereiden ticalb etw eenth etwo in m edi evalandR en aiss an ceEu rop e .So
Theth ri
ft yg en eh ypoth e
sisp rovidesan popu lation s.In s
tead,on em easu resth e la cko fe xpo su r eto fam in es eem sun lik elyto
expl anat
ionfo r wh y hum ansing ener a
l prev a
l en ceinapopu l ationa safun ctiono f beanan sw er.
bec omep r onetodiabetesund eraw e
ste
rni zed age,th enc alcula
teswh atthep revalen cewou ld Inst ead,a mo rep rom i sin gh ypo th esisis
li
fe s
t y
le.Bu twh y
,inlighto fthishypoth e
sis, befo rth a
twho lepopu lation ifith adac ertain bas edonEu rop e’sr ecen tfoodh is to ry( see
areN auru ansand A rizon aP im aInd ians stand a rdizeda gedi stribu t
ion 30
.(Fromr ef
s5 ,3 0 alsor ef.2 8fo rano th erv iew )
.Th ep eriod ic
exp eri
en cin gespeci
allys evereepidemicso f ando th ersou rces
.) wid espr eadand p ro lon gedf am in esth at
typ e2d iab eteswhileEu rop eanpopulations usedtow rac kEu rop e
,l i keth er esto fth e
—inEu rop eande l
sewh ere —h a
veuniqu ely foundedb yp eopl
e whound ertookin te
r- wo rld,d isapp e aredb etw eenabou t1 6 50and
lowp revalen ce
s? is
landc anoev o
yageslast
ingsevera
lw eeks
. 19 0 0a td if
fe ren tt im esind ifferen tp arts
Nau ru N au ruans suffered tw oe x
trem e In num erousa t
test
ed e xampl
eso fsu ch ofEu rop e —th el ate1 60 0sinB rit a
inand
bou tsofn aturalse
lect
ionfo rthrif
tyg ene s
, lengthyvoya
ges,m anyor mostofthec anoe th eN eth erland s,fo re xamp le,andth el at
e
follow ed b y an e xt
rem e bouto fc oc a
- occupant
sdiedofstarva
tion,andonlytho se 18 0 0
sinsou th ern F r an c eandsou th ern
7 23–27
colon i
z a
tion . F i
rst
,l ike o ther P a c
ific who w er
eo r
iginal
lyth ef a
tte
stsu rvived
. Ital y . W ith on ef amou se xcep tion,
Is
l ande r
s —bu tunliketh einh abi
tantso f ThatiswhyP a
cif
icIsl
and er
singen e
raltend Eu rop e’sfam in esw e reend edb yacomb in a-
con t
inen talr eg
ions —th ei
rpopu lat
ionw a
s tob eh ea
vyp eop
le.S e
c ond
,theN auruans tiono fth reeo rfou rf a ctor s
:in cr easin g
ly
NATURE|VOL4
23|5
JUNE2
003|www
.na
tur
e.com
/na
tur
e © 2003Na
turePub
lish
ingG
roup 601
news and views feature
efficient state intervention that rapidly
redistributed any surplus grain to famine
areas; increasingly efficient food transport
by land and especially by sea; increasingly
diversified agriculture after AD 1492, a con-
sequence of the advent of crops, such as
potatoes and corn (maize), which were
brought back by European voyagers and
broadened the base of European agricul-
ture, thereby reducing the risk of starvation
from failure of a single crop; and finally per-
haps, Europe’s reliance on ‘rain agriculture’,
which reduced the risk of a crop failure that
was too widespread to be solved by food
transport within Europe, rather than (as in
many populous areas outside Europe) ‘irri-
gation agriculture’. The famous exception is,
of course, the Irish potato famine of the
1840s. But this may be the exception that
proves the rule. The potato famine was
due to a disease of one crop in an economy
that was unusual in Europe in its reliance
on that single crop, and it occurred on
an island governed by a state centred on
another island.
A cryptic epidemic in Europe? A corollary
of this view based on Europe’s food history is
that, several centuries before the advent of
modern medicine, Europeans, like modern
Nauruans, should have undergone an epi-
demic in type 2 diabetes that resulted from
the new reliability of adequate food supplies
and eliminated most diabetes-prone bearers
of the thrifty genotype. However, there
would have been big differences between
that postulated earlier European epidemic
and the well-documented modern epi-
demics among Nauruans and among so
many other peoples today. In the modern
epidemics, abundant and continually reliable
food arrived suddenly, within a decade for
the Nauruans and within just a month for the
Yemenite Jews. The result was a sharply
peaked surge in prevalence to 20–50% that
occurred right under the eyes of modern dia-
betologists. That increase will probably wane
quickly, as individuals with the thrifty geno-
type become eliminated by natural selection
within a mere generation or two. In contrast,
Europe’s food abundance would have
increased gradually over the course of several
centuries, and the result, between the 1400s
and 1700s, would have been a slow rise in
type 2 prevalence long before there were
diabetologists to take note.
A possible victim of this postulated
cryptic epidemic of diabetes was the com-
poser Johann Sebastian Bach (1685–1750).
Bach’s medical history is too poorly docu-
mented to permit certainty as to the cause
of his death. Nonetheless, the corpulence of
his face and hands in the sole authenticated
portrait of him, the accounts of deterior-
ating vision in his later years, and the evident
deterioration of his handwriting, possibly
secondary to his failing vision, are consis-
tent with a diagnosis of type 2 diabetes. The
602
disease certainly occurred in Germany
during Bach’s lifetime, being known as
“honigsüsse Harnruhr ” (honey-sweet urine
disease)29.
Tests of the hypotheses
These ideas about the evolution of type 2
diabetes can be tested. Here are some of the
questions that can be asked, and predictions
that can be tested.
● How much evidence is there for the postu-
lated epidemic of diabetes in late medieval
and Renaissance Europe, either in individual
biographies (as that of Bach) or in contem-
porary medical treatises? Did the timing of
the epidemic vary locally with the different
times for the disappearance of famines in
different parts of Europe? Was a diabetes
epidemic evident after the Black Death,
when human population declined much
more rapidly than did food availability?
● The prevalence of type 2 diabetes in Euro-
pean immigrants of British and German
ancestry to the United States and Australia is
reported as 7–8%, much higher than the 2%
for British and German people still living in
Europe today under similar lifestyles. This dif-
ference is consistent with the socially stratified
emigration often discussed by historians. The
Europeans who stayed at home tended to be
richer than those who emigrated;in the former
group, the genotype predisposing the bearer
to type 2 diabetes may have already been
selected out by centuries of abundant food,
whereas those who emigrated may have been
the starvation-prone poor who still carried
the thrifty genotype3. This possibility could be
tested by controlled comparison of modern
Europeans still living in Europe with overseas
Europeans whose ancestors’ country of origin
and date of emigration are known. As a specif-
ic example, are overseas descendants of Irish
emigrants in the 1840s more susceptible to
diabetes than are Ireland’s inhabitants today?
● In pre-modern times, the risk of famine
was higher in the drought- and flood-prone
northern areas of China than in the south. Is
there a corresponding difference in predis-
position to diabetes? And did China’s
famines during the Great Leap Forward of
the late 1950s produce additional selection
for thrifty genes?
● Were the risks of famine, and so selection
for thrifty genes, higher in societies that
depended heavily on fishing and hunting-
and-gathering (Nauruans, Pimas and Abo-
riginal Australians, for instance) than in
farming societies in which food storage had
become the norm (Europe and China)?
● Are genetic susceptibility factors for type 2
diabetes especially evident in Nauruans,
Yemenite Jews and other populations show-
ing recent surges of the disease?
● Anecdotal accounts suggesting that there
were other modern epidemics of diabetes
deserve investigation. For instance, a col-
league whose grandfather was from northern
© 2003 Nature Publishing Group
Iran recounts that improved food transport
there in the early 1900s reduced the frequency
of starvation and triggered a diabetes
epidemic, especially among rich people —
hence the local term ‘the rich man’s disease’.
● Medical geneticists seek to identify and pre-
emptively counsel people carrying suscepti-
bility factors for specific diseases. Can Third
World populations, whose history of marked
swings between food and starvation puts them
at risk of diabetes with the spread of coca-
colonization, be likewise identified and pre-
emptively counselled by public-health offi-
cials? That might spare them the fate of the
Nauruans, Arizona Pima Indians and Wani-
gela. The evolutionary history and geography
of type 2 diabetes would then have provided
us not only with a double puzzle, but also
with insights that could potentially help save
millions of people from premature death. ■
Jared Diamond is in the Departments of Geography
and Environmental Health Sciences, University of
California, Los Angeles, 1255 Bunche Hall, Box
951524, California 90095-1524, USA.
e-mail: jdiamond@geog.ucla.edu
1. Levitt, N. et al. Diabetes Care 16, 601–607 (1993).
2. Zimmet, P., Alberti, K. & Shaw, J. Nature 414, 782–787 (2001).
3. Zimmet, P. in The Medical Challenge: Complex Traits (eds
Fischer, E. & Moller, G.) 55–110 (Piper, Munich, 1997).
4. Zimmet, P. J. Intern. Med. 247, 301–310 (2000).
5. King, H., Aubert, R. & Herman, W. Diabetes Care 21,
1414–1431 (1998).
6. Dowse, G., Zimmet, P., Finch, C. & Collins, V. Am. J. Epidemiol.
133, 1093–1104 (1991).
7. Rubinstein, H. & Zimmet, P. Phosphate, Wealth, and Health in
Nauru: A Study of Lifestyle Change (Brolga, Gundaroo, 1993).
8. Knowler, W., Pettitt, D., Saad, N. & Bennett, P.
Diabetes Metab. Rev. 6, 1–27 (1990).
9. Dowse, G. et al. Med. J. Aust. 160, 767–774 (1994).
10. Gardner, L. et al. Diabetes 33, 86–92 (1984).
11. Elbein, S., Chiu, K. & Permutt, M. in The Genetic Basis of
Common Diseases 2nd edn (eds King, R., Rotter, J. & Motulsky,
A.) 457–480 (Oxford Univ. Press, 2002).
12. Raffel, L. & Rotter, J. in Principles and Practice of Medical
Genetics Vol. 2, 4th edn (eds Rimoin, D., Connor, J. & Pyeritz,
R.) 2231–2276 (Churchill Livingston, London, 2001).
13. Hales, C. & Barker, D. Diabetologia 35, 595–601 (1992).
14. Zimmet, P. Diabetes Care 15, 232–252 (1992).
15. Campbell, G. S. Afr. Med. J. 37, 1195–1207 (1963).
16. Coleman, D. Science 203, 663–665 (1979).
17. Dowse, G. K. et al. Diabetes 39, 390–396 (1990).
18. Diamond, J. Nature 410, 521 (2001).
19. Neel, J. Am. J. Hum. Genet. 14, 353–362 (1962).
20. Neel, J. in The Genetics of Diabetes Mellitus (eds Kobberling, J. &
Tattersall, J.) 283–293 (Academic, New York, 1982).
21. Haines, H., Hackel, D. & Schmidt-Nielsen, K. Am. J. Physiol.
208, 297–300 (1965).
22. Russell, F. The Pima Indians (Univ. Arizona Press, Tucson, 1975).
23. Appleby, A. Famine in Tudor and Stuart England (Stanford
Univ. Press, 1978).
24. Jordan, W. The Great Famine: Northern Europe in the Early
Fourteenth Century (Princeton Univ. Press, 1996).
25. Monahan, W. Year of Sorrows: The Great Famine of 1709 in Lyon
(Ohio State Univ. Press, Columbus, 1993).
26. Post, J. Food Shortage, Climatic Variability and Epidemic Disease
in Preindustrial Europe (Cornell Univ. Press, Ithaca, 1985).
27. Rotberg, R. & Rabd, T. (eds) Hunger and History: The Impact of
Changing Food Production and Consumption Patterns on Society
(Cambridge Univ. Press, 1983).
28. McMichael, A. Human Frontiers, Environments and Disease: Past
Patterns on Certain Futures (Cambridge Univ. Press, 2001).
29. Kranemann, D. Bach Jahrbuch 53–64 (1990).
30. King, H. & Rewers, M. Diabetes Care 16, 157–177 (1993).
It is a pleasure to acknowledge my debt for fruitful discussions
about diabetes with Paul Zimmet and Jerome Rotter, and about
European food history with Jack Goldstone and William Jordan.
NATURE | VOL 423 | 5 JUNE 2003 | www.nature.com/nature