Bruce B . Duncan
C entral obesity and the insulin resistance
syndrom e -
new elem ents in the etiology of
non-communicable diseases
Departamento
de Medicina Social, UFRGS
M ajo r ad v an ces in o u r u n d erstan d in g o f card io v ascu lar
an d o th er ch ro n ic d iseases are im p o rtan t fo r th e h ealth o f
B razilian s. B razilian ad u lt p o p u latio n s, in ag e stan d erd ized
in tern atio n al co m p ariso n s, h av e so m e o f th e h ig h est card io
-v ascu lar d isease rate rep o rted . T h ese h ig h rates are d u e in
larg e p art, I b eliev e, to o u r lack o f atten tio n to th e p ro b lem . In
in fan t h ealth , id en tified as a n atio n al p rio rity , th e resu lts o f
th e last 1 5 y ears are d ram atical1 y fav o rab le. T h e sam e can
an d m u st b e d o n e fo r ad u lt h ealth , fo r stu d ies o f d ev el9 p in g
co u n tries in g en eral, an d B razil in p articu lar, h av e sh o w n th at
th e ch an g in g d em o g rap h ic p attern w ill g reatly in crease th e
co u n try 's h ealth b u rd en , p ro d u cin g an in creasjn g p red o m
i-n ai-n ce o f ch ro i-n ic ad u lt d iseases.
In th is reg ard , w h at h av e w e learn ed recen tly th at m ay
h elp u s p rev en t th ese d iseases? O n e th in g is th at p ast
ap p rao ch es are in ad eq u ate. S tu d ies sh o w th at p rev io u s reco m
-m en d atio n s fo r ag ressi v e th erap y o f h y p erten sio n an d
h y p erch o lestero lem ia are in efficien t w ay s o f p rev en tin g co ro
-n ary d eath s. P ro b ab ly less th an h alf o f h y p erten siv es treated
b y p rev io u s criteria sh o u ld receiv e p h arm aco lo g ic treatm en t
b y to d ay 's stan d ard s, an d recen t m eta-an aly ses su g g est th at
th e treatm en t o f asy m p to m atic h y p erch o lestero lem ia, b esid es
co stin g a fo rtu n e, m ay d o m o re h arm th an g o o d . A recen t
M O N IC A S tu d y sh o w ed th at o n ly 2 5 % o f v ariab ility in
isch em ic h eart d isease co u ld b e ex p lain ed b y d ifferen ces in
th e d istrib u tio n acro ss co u n tries o f th e trad itio n al risk facto rs
sm o k in g , b lo o d p ressu re an d ch o lestero l.
Id en tificatio n an d treatm en t o f h y p erten sio n an d
h y p erch o lestero lem ia h av e b een , fo r th e last d ecad e, th e co
r-n ersto r-n es o f clir-n icial p rev er-n tiv e th erap y aim ed at th o se w ith
h em o d y n am ic an d m etab o lic risk fo r h eart d isease. H y p
er-ten sio n can b e effectiv el1 y m an ag ed , b u t w e can 't ex p ect to o
m u ch in retu rn . F u rth er, g iv en th e d ifficu lty o f cen terin g a
clin ical strateg y to red u ce m etab o lic risk o n ch o lestero l, w e
n eed n ew ap p ro ach es w h ich can id en tify p atien ts m etab o
li-cally at risk early o n in th eir liv es so th at w e m ay targ et th em
fo r n o n -p h arm aco lo g ic th erap ies. O n e p o ten tial ap p ro ach m ay
b e related to o b esity , cen tral o b esity an d th e in su lin resistan ce
sy n d ro m e.
A n atio n al p u b lic h ealth d isaster is o cu rrin g w ith
res-p ect to o b esity . It's res-p rev alen ce in creased 1 0 0 % in B razilian
m en an d 7 0 % in B razilian w o m en o v er a p erio d o f 15 y ears
en d in g in 1 9 8 9 . C u rren tly 4 8 % o f B razilian w o m en , b y W o rld
H ealth O rg an zatio n criteria, are ab o v e n o rm al w eig h t. O n e
q u arter o f th ese w o m en are fran k ly o b ese.
O b esity h as b een sh o w n to in crease th e risk o f h y p
er-ten sio n , d y slip id em ia an d d iab etes. H o w ev er, its real im p o
r-tan ce in cau sin g d eath is u n clear. R ecen t stu d ies su g g est th at
th e b o d ily lo calizatio n o f ad ip o se tissu e, sp ecifically cen tral,
o f v isceral ex cess, is m u ch im p o rtan t to o v erral o b esity . In a
stu d y o f o v er 4 0 ,0 0 0 U .S . w o m en , w h en th e w aist-to -h ip
ra-tio (W H R ) - a m easu re o f cen tral o b esity - w as g reater
th an 0 .9 0 , th e risk o f th e d eath w as d o u b led , co m p ared to
w h en ratio w as less th an 0 .7 6 . S im ilar fin d in g s, th o u g h n o t as
stro n g , h av e b een fo u n d fo r m en . D ata fro m P o rto A leg re
sh o w s th e im p o rtan ce o f th e asso ciatio n b etw een cen tral o b
e-sity an d d iab etes. In an aly ses co n tro llin g fo r ag e, fam ily h
is-to ry o f d iab etes an d o v eral1 o b esity , w o m en w ith a h ig h W H R
h ad alm o st fiv e tim es th e p rev alen ce o f d iab etes o f th o se w ith
lo w W H R , m en m o re th an tw o tim es th e p rev alen ce. U .S .
stu d ies sh o w w o m en w ith h ig h W H R to b e at g reater risk
b reas fo r it can cer; m en , fo r co lo n can cer.
W h ere d o es in su lin resistan ce fit in ?
Insulin sensitivity
can b e th o u g h t o f co n cep tu al1 y as th e facility w ith w h ich th e
b o d y m atab o lizes a g lu co se lo ad .
Insulin resistance
is th e o p p o site o f in su lin sen sitiv ity . M etab o lic stu d ies, u sin g so-called g lu co se clam p tech n iq u es, h av e co n firm ed th at su ch
resistan ce is a m ajo r p red icto r o f d iab etes, an d h av e so also
d o n strated a h ig h freq u en cy o f in su lin resistan ce in ad u lts w ith
lesser d eg rees o f g lu co se in to leran ce, as w el1 as in m an y g lu
-co se to leran t in d iv id u als. In su lin resistan ce is in tim ately
re-lated to cen tral o b esity , an d m ay b e m o re d irectly in v o lv ed in
th e etio lo g y o f ch ro n ic d isease. E p id em io lo g ic stu d ies, u sin g
v ario u s m ark ers o f resistan ce, h av e d em o n strated an im p o
r-tan t clu sterin g o f card io v ascu lar risk facto rs w ith th is
resis-tan ce. T o m en tio n o n e, in th e A R IC stu d y o f o v er 1 2 0 0 0 U .S .
m id d le ag ed ad u lts, th e d istrib u tio n o f six ab n o rm alities
-h y p erten sio n , d iab etes m el1 itu s, h ig h L D L -C , h ig h trig ly
rides, low H D L-C and high uric acid -' factors associated
w ith ischem ic heart disease - w as studied. A lthoug overall obesity, central obesity and fasting insulin all contributed in
an independent m anner to this clustering, the association w ith insulin w as m ost notable. In w hite w om en, w here the
associa-tions are strongest, the risk of having three or m ore of these abnorm alities w as 6 tim es higher in those w ith high fasting
insulin, of having 4 or m ore, 12 tim es higher. Serum insulin levels, a surrogate m easure of insuline resistance, have been
show n to predict the developm ent of hypertesion as w ell as of diabetes.
H ow m ight central obesity and the insulin resistance syndrom e be used in a prevention program for those at m eta-bolic risk for chronic disease?
Through identifying central obesity, and perhaps screen-ing biochem ically for insulin resistance, individuals m etaboli-cally at high risk could be identified. Interventions in these
individuals w ould then be aim ed at helping them stay healthy, using standard approaches such as increased physical activ-ity and w eigth m aintenance or loss - w hich current evidence
show s are not im possible tasks for m any patients - and new er interventions, such as stim ulating m oderate alcohol consum
p-tion, and diets w ith anti-oxidant, anti-atherogenic and anti-throm bogenic properties. D ietary therapies have been show n
in random ized trials to be successful in prevention of coro-nary disease, at least in trials of secondary prevention. A ll of the above factors have strong inverse assoCiations w ith
ischem ic heart disease in cohort studies. A ll can be adm inis-tered as health prom otion activities, w ithout labeling these high risk individuals as diseased. These interventions, w hich
are m erelr intensified variants of w hat, to one degree or an-other, can be general health prom otion strategies for adults, can be im plem ented presum ably at a fraction of the cost of later pharm acologic interventions.
Before launching such a program m uch further research is needed. But this approach appears to hold m uch prom ise. The current m ix of prevention and therapy for chronic di-seases w ithin the SU S is w eighted too m uch tow ard therapy.
W e need to be constantly looking for w ays to change this picture.
