Diabetes Mellitus Type 2 and Colorectal Cancer

Tessi Ananditya
030.04.217
Faculty of Medicine
Trisakti University
2008
PREFCE
Bismillaahir Rahmaanir Rahiim
First, I would like to e!ress my "ratitude #or Allah $%T #or &is 'less so I (an #inish my
task. $e(ondly, my 'elo)ed !arents who a((ommodated me to #inish all this task. Third, I
would like to "i)e my "ratitude to my su!er)isor, *ro#. +r. ,ulius -. $ur.awid.a.a,
$!./0, who has "uidin" me all alon". 1ast 'ut not least, I would like to thank to all o#
my #riends, thank you #or your hel! and attention.
This !a!er title is !+ia'etes /ellitus Ty!e 2 and 2olore(tal 2an(er"# This !a!er is made
to (om!lete -n"lish assi"nment #or su'.e(t /edi(al -n"lish 3 in the Fa(ulty o# /edi(ine,
Trisakti 3ni)ersity.
I ho!e this !a!er (an 'e use#ul #or e)eryone "enerally and es!e(ially #or e)eryone who
read this !a!er, I am sure my !a!er is not !er#e(t, (riti(s #rom you will 'e moti)ated me
to 'e 'etter net day.
C$%TE%T&
*re#a(e
i
2ontents ii
A'stra(t iii
2ha!ter I 4 Introdu(tion 1
2ha!ter II 4 +is(ussion 2
2ha!ter III 4 2on(lusion 4
Re#eren(es 5
A'stra(t
+ietary and li#estyle #a(tors related to insulin resistan(e

and hy!erinsulinemia,
in(ludin" a westerni6ed diet, !hysi(al

ina(ti)ity, and o'esity, ha)e 'een linked to
in(reased (olore(tal

(an(er risk. These o'ser)ations su!!ort the hy!othesis

that
hy!erinsulinemia or #a(tors asso(iated with insulin

resistan(e, su(h as hy!er"ly(emia or
hy!ertri"ly(eridemia,

may !lay a role in (olore(tal (ar(ino"enesis. -!idemiolo"i(

studies
ha)e o'ser)ed an ele)ated risk o# (olore(tal (an(er

asso(iated with hi"h (ir(ulatin"
insulin, I7F81, and 28!e!tide 9a marker

o# insulin se(retion: (on(entrations.
2&A*T-R I
I;TR<+32TI<;
Re(ent studies shows that +ia'etes /ellitus ty!e 2 si"ni#i(antly ele)ates a
!erson=s li#etime risk o# (olore(tal (an(er. This asso(iation !ersisted e)en a#ter
ad.ustment o#

other (olore(tal (an(er risk #a(tors in(ludin" 'ody mass inde

9B/I:,
!hysi(al a(ti)ity, s(reenin" !atterns, and dietary #a(tors.

Althou"h +ia'etes /ellitus ty!e
2 (ould in#luen(e (olore(tal (ar(ino"enesis throu"h

se)eral me(hanisms, ele)ated le)els
o# 'oth (ir(ulatin" !ost!randial

insulin and 28!e!tide ha)e 'een shown to in(rease
(olore(tal

(an(er risk.
In (ontrast, the in#luen(e o# dia'etes mellitus on the lon"8term

out(ome o# !atients
with esta'lished (olon (an(er remains un(ertain.

/oreo)er, 'e(ause

in#ormation
re"ardin" (an(er rela!se was not a)aila'le, it remained

un(lear whether the in#luen(e o#
dia'etes was dire(tly related

to a hi"her rate o# (an(er re(urren(e.
2&A*T-R II
+I$23$$I<;
+ia'etes /ellitus 9+/: (om!rises a "rou! o# (ommon meta'oli( disorders that
shares !henoty!e o# hy!er"ly(emia. +/ is (lassi#ied on the 'asis o# !atho"eni( !ro(ess
that leads to hy!er"ly(emia. The two 'road (ate"ories o# +/ are desi"nated ty!e 1 and
ty!e 2.
Ty!e 2 +/ is a hetero"eneous "rou! o# disorders (hara(teri6ed 'y )aria'le
de"rees o# insulin resistan(e, im!aired insulin se(retion, and in(reased "lu(ose
!rodu(tion. Insulin resistan(e im!airs "lu(ose utili6ation 'y insulin8sensiti)e tissues and
in(rease he!ati( "lu(ose out!ut> 'oth e##e(ts (ontri'ute to the hy!er"ly(emia. Insulin
se(retion and sensiti)ity are interrelated. In ty!e 2 +/, insulin se(retion initially
in(reases in res!onse to insulin resistan(e to maintain normal "lu(ose toleran(e.
2olore(tal (an(er, also (alled (olon (an(er or lar"e 'owel (an(er, in(ludes
(an(erous "rowths in the (olon, re(tum and a!!endi. /ost (olore(tal (an(er, re"ardless
o# etiolo"y, arise #rom adenomatous !oly!s.
The etiolo"y #or most (ases o# lar"e8'owel (an(er a!!ears to 'e related to
en)ironmental #a(tors. The disease o((urs more o#ten in u!!er so(ioe(onomi(
!o!ulations who li)e in ur'an area. /ortality #rom (olore(tal (an(er is dire(tly (orrelated
with !er (a!ita (onsum!tion o# (alories, meat !rotein, and dietary #at and oil as well as
ele)ated serum (holesterol (on(entration and mortality #rom (oronary disease.
There are some risk #a(tors #or de)elo!ment o# (olore(tal (an(er. <ne o# it is
insulin resistan(e. The num'er o# (alories inherent in westerni6ed diets (ou!led with
!hysi(al ina(ti)ity ha)e 'een asso(iated with hi"her !re)alen(e o# o'esity. *ersons with
su(h e(ess wei"ht "ain de)elo! insulin resistan(e with in(reasin" (ir(ulatin" le)el o#
insulin, leadin" to hi"her (ir(ulatin" (on(entration o# insulin8like "rowth #a(tors ty!e I
9I7F81:. This #a(tors a!!ears to stimulate !roli#eration o# the intestinal mu(osa.
I7F81 is a !oly!e!tide !rotein hormone similar in mole(ular stru(ture to insulin.
It !lays an im!ortant role in (hildhood "rowth and (ontinues to ha)e ana'oli( e##e(ts in
adults
The e##e(ts o# dia'etes mellitus on (olore(tal (an(er may 'e

mediated throu"h
me(hanisms ran"in" #rom in(reased (oloni( transit

time to hy!erinsulinaemia. In relation
to the latter, at least

in the early !hase o# de)elo!ment, ty!e 2 dia'etes mellitus

is
asso(iated with in(reased (ir(ulatin" insulin (on(entrations.

Insulin may stimulate (ell
!roli#eration throu"h two !athways4

a minor !athway that entails dire(t a(ti)ation o# the
insulin

re(e!tor or insulin8like "rowth #a(tor 9I7F:8I re(e!tor, and

a ma.or !athway )ia
inhi'ition o# I7F 'indin" !roteins 9in !arti(ular,

I7FB*81 and I7FB*82:, resultin"
theoreti(ally in in(reased 'ioa)aila'ility

o# I7F8I to the I7F8I re(e!tor. 2lini(al studies
also inde!endently

link hi"h (ir(ulatin" (on(entrations o# 28!e!tide, as a marker

o#
insulin !rodu(tion, with in(reased (olore(tal (an(er risk.
Insulin and insulin8like "rowth #a(tor 9I7F: aes are ma.or

determinants o#
!roli#eration and a!o!tosis and thus may in#luen(e

(ar(ino"enesis. In )arious animal
models, modulation o# insulin

and I7F81 le)els throu"h )arious means, in(ludin" dire(t
in#usion,

ener"y e(ess or restri(tion, "eneti(ally indu(ed o'esity, dietary

?uality
in(ludin" #atty a(id and su(rose (ontent, inhi'ition

o# normal insulin se(retion and
!harma(olo"i( inhi'ition o#

I7F81, in#luen(es (oloni( (ar(ino"enesis. &uman e)iden(e
also

asso(iates hi"h le)els o# insulin and I7F81 with in(reased risk

o# (olon (an(er.
2lini(al (onditions asso(iated with hi"h le)els

o# insulin 9noninsulin8de!endent
dia'etes mellitus and hy!ertri"ly(eridemia:

and I7F81 are related to in(reased risk o#
(olon

(an(er, and in(reased (ir(ulatin" (on(entrations o# insulin

and I7F81 are related to
a hi"her risk o# (oloni( neo!lasia.

+eterminants and markers o# hy!erinsulinemia
9!hysi(al ina(ti)ity,

hi"h 'ody mass inde, (entral adi!osity: and hi"h I7F81 le)els

are
also related to hi"her risk. /any studies

indi(ate that dietary !atterns that stimulate
insulin resistan(e

or se(retion, in(ludin" hi"h (onsum!tion o# su(rose, )arious

sour(es o#
star(h, a hi"h "ly(emi( inde and hi"h saturated

#atty a(id intake, are asso(iated with a
hi"her risk o# (olon

(an(er.
2&A*T-R III
2<;213$I<;
2han"in" li#estyle o# westerni6ed diet, !hysi(al

ina(ti)ity, and o'esity, leads to
hy!er"ly(emia whi(h leads to hi"her se(retion o# insulin. <n lon" term e##e(t it will
(aused Ty!e 2 +ia'etes /ellitus.
Ty!e 2 +/ is (hara(teri6ed 'y insulin resistan(e and im!aired insulin se(retion. This
will (aused hi"her insulin and I7F81 (ir(ulation in 'lood.
Insulin and insulin8like "rowth #a(tor 9I7F: aes are ma.or

determinants o#
!roli#eration and a!o!tosis and thus may in#luen(e

(ar(ino"enesis.
R-F-R-;2-$
1. As!lin, ,ohn R., Fredri( 1. 2oe, /urray ,. Fa)us. In 0as!er, Braunwald, Fau(i,
&auser, 1on"o, ,ameson. &arrison=s *rin(i!les o# Internal /edi(ine 1@
th
-dition,
2005
2. %ill ,2, 7aluska +A, Aini(or F, 2alle --. 2olore(tal (an(er4 another
(om!li(ation o# dia'etes mellitusB Am J Epidemiol 1CCD>1474 D1@825
3. /eyerhardt ,A, 2atalano *,, &aller +7, /ayer R,, /a(donald ,$, Benson AB
3rd, et al. Im!a(t o# dia'etes mellitus on out(omes in !atients with (olon (an(er.
J Clin Oncol 2003>214 433840
4. /a ,, 7io)annu((i -, *ollak /, 1ea)itt A, Tao E, 7a6iano ,/, et al. A
!ros!e(ti)e study o# !lasma 28!e!tide and (olore(tal (an(er risk in men. J Natl
Cancer Inst 2004>C@4 54@853
5. Ean" EF, &ennessy $, 1ewis ,+. Insulin thera!y and (olore(tal (an(er risk
amon" ty!e 2 dia'etes mellitus !atients. Gastroenterology 2004>1274 1044850