‫ﻴﻢ‬

‫ﺮﺣ‬‫ﻟ‬
‫ﺍ‬‫ﻤﻦ‬
‫ﺮﺣ‬‫ﻟ‬
‫ﺍ‬‫ﺑﺴﻢ ﷲ‬
AGr
aduat
ionResear
chPr
oject
AssessmentofHi
ghDensi
tyLipopr
otei
ninCont
rol
led
andUncontr
oll
edDi
abet
icPati
entsinWadMadani,2019
By
:
RawanHat
im Al
shei
khAl
i
Bat
ch38
AGr
aduat
ionResear
chPr
ojectSubmi
tt
ed
Par
ti
alFul
fi
ll
mentf
ort
heRequi
rement
sofB.
S.CHonor
Degr
eei
nMedi
calLabor
ator
ySci
ences

Depar
tmentofCl
ini
calChemi
str
y

Facul
tyofMedi
calLabor
ator
ysci
ence

Uni
ver
sit
yofGezi
ra

Super
visor
:

U:Shat
haEl
tay
ebEl
magzoub
 Chapt
erone
1.
Int
roduct
ion:

1.
1Gener
alI
ntr
oduct
ion:

Di
abet
esmel
l
itusi
s a gr
oup ofmet
abol
i
cdi
sease char
act
eri
zed by
i
ncr
easebl
oodgl
ucosel
evelr
esul
ti
ngf
rom def
ect
sini
nsul
i
nsecr
eti
on,
insul
i
n
act
ion,
orbot
h(Ut
traetal
,2011)
.
Thepr
eval
enceofdi
abet
esmel
l
itusi
nmi
ddl
eeastandnor
thAf
ri
cawas
est
imat
edt
obear
ound25%.
Mor
eal
armi
ngi
sfatt
hatnumberofi
ndi
vi
dual
s
af
fect
edbydi
abet
esmel
l
itusi
nAf
ri
cawi
l
lincr
easef
rom 14mi
l
li
oncur
rent
ly
t
o28mi
l
li
onbyt
hey
ear2030.
thepr
eval
enceofdi
abet
esi
nur
banar
eai
n
nor
thSudani
sest
imat
edt
obear
ound19%.
fur
ther
mor
e,t
henor
thofSudan
was8.
3%.
Thepr
eval
enceofundi
agnoseddi
abet
esi
nrur
alcommuni
ti
esof
nor
th Sudan was2.
6%and gl
ucoset
oler
ancewas1.
6%.
thepr
eval
enceof
uncont
rol
l
eddi
abet
esi
sani
mpor
tanti
ssuef
orl
owi
ncome,mi
ddl
eandhi
gh
i
ncomecount
ri
es,f
orexampl
einsi
xAf
ri
cancount
ri
est
heav
erageofgood
gl
ycemi
ccont
rolwasnot
edi
nonl
y29%.
inEt
hiopi
athepr
eval
enceofpoor
di
abet
eswasbet
ween64.
7and82,
i
nTanzani
awas61.
3.r
ichcount
ri
esl
i
ke
Chi
naandJapanar
eel
sest
ruggl
i
ngt
oachi
evegooddi
abet
escont
rolf
or
i
nst
ancei
nJapant
hepr
eval
enceofgooddi
abet
escont
rolwas44.
9%.
andi
n
Chi
nagooddi
abet
escont
rolwasachi
evei
n41% oft
hosei
ninsul
i
nther
apy
Nooretal
( ,2016)
.
Di
abet
esi
scl
assi
fi
edi
ntot
ype1di
abet
esmel
l
ituspr
evi
ousl
ycal
l
edi
nsul
i
n
–dependentdi
abet
es mel
l
itus,i
tusual
l
y pr
esent
s dur
ing chi
l
dhood or
adol
escence.Mostoft
hesecasei
sduet
oimmune-
medi
atedpr
ocessand
maybeassoci
atedwi
thot
heraut
oimmunedi
sor
der
s.I
thasbeensuggest
ed
t
hatmaycasesf
oll
ow av
irali
nfect
iont
hathasdamagedt
heB-
cel
l
soft
he
pancr
eat
ici
slet
s.Ty
pe 2 di
abet
es mel
l
itus pr
evi
ousl
ycal
l
ed non-
insul
i
n-
dependentdi
abet
es mel
l
itus,t
hist
he mostcommon v
ari
ety wor
ldwi
de.
Pat
ient
sar
emuchl
essl
i
kel
ytodev
elopket
oaci
dosi
sthant
hosewi
tht
ype1
di
abet
es,al
thoughi
nsul
i
nmaysomet
imesbeneed.Onseti
smostusual
dur
ingadul
tli
fe,t
her
eisaf
ami
l
ialt
endencyandassoci
ati
onwi
thobesi
ty.
Ot
herspeci
fi
cty
pesofdi
abet
esmel
l
itus.Gest
ati
onal
diabet
esmel
l
itus(
Crook,
2012)
.
Theoccur
renceofdi
abet
esmel
l
itusi
sduet
ochr
oni
chy
per
gly
cemi
aand
di
sor
deri
ncar
bohy
drat
e,f
atandpr
otei
nmet
abol
i
sm,whi
chi
srel
atedt
othe
pr
ogr
essi
on ofmi
cro-
macr
ovascul
arcompl
i
cat
ion such as car
diov
ascul
ar
di
sease,r
eti
nopat
hies,neur
opat
hiesandneur
opat
hiest
hisdi
seasei
scaused
byt
heexi
stenceofabsol
uteandr
elat
ivei
nsul
i
ndef
ici
ency
.Themoni
tor
ingof
di
abet
esmel
l
ituscanbedoneusi
ngt
hehemogl
obi
nA1ct
hatr
esul
tinHbA1c
t
akespl
acei
ner
ythr
ocy
teandi
sdependi
ngont
hel
evelofgl
ucosef
or120
day
s,whi
chcor
respondst
oer
ythr
ocy
tel
i
fespan.I
nspect
ionofhemogl
obi
n
A1C wi
l
lref
lectt
olong-
rangedi
abet
esmel
l
ituscont
rolov
ert
hree-
mont
h
per
iod(
Susant
ietal
,2010)
HDL,
thesmal
l
estanddensestl
i
popr
otei
nissy
nthesi
zedbybot
hthel
i
verand
i
ntest
ine.HDLcanexi
stasei
therdi
sk-
shapedpar
ti
clesor
,mor
ecommonl
y,
spher
icalpar
ti
cle.Di
scoi
dalHDLt
ypi
cal
l
ycont
ainst
womol
ecul
esofapoA-
1,
whi
ch f
orm ar
ing ar
ound a cent
rall
i
pid bi
l
ayer
.Ofphosphol
i
pid and
chol
est
erol
.Di
scoi
dalHDLi
sbel
i
evedt
orepr
esentnascentornewl
ysecr
eted
HDL and i
sthe mostact
ivef
orm i
nremov
ing excess chol
est
erolf
rom
per
ipher
alcel
l
.Theabi
l
ityofHDLt
oremov
echol
est
erolf
rom cel
l
,cal
l
ed
r
ever
sechol
est
erolt
ranspor
t,i
soneoft
hemai
nmechani
smspr
oposedt
o
expl
aint
he ant
i-
ather
ogeni
c pr
oper
ty ofHDL.When di
scoi
dalHDL has
acqui
redanaddi
ti
onall
i
pid,chol
est
ery
lest
erandt
ri
gly
cer
idesf
orm acor
e
r
egi
onbet
weeni
tsphosphol
i
pidbi
l
ayer
,whi
cht
ransf
ormsDi
scoi
dalHDLi
nto
spher
ical hi
gh-
densi
ty l
i
popr
otei
n. Hi
gh-
densi
ty l
i
popr
otei
n i
s hi
ghl
y
het
erogeneousi
nsi
zeandl
i
pidandpr
otei
ncomposi
ti
onandi
ssepar
abl
eint
o
asmanyas13or14di
ff
erentbasedondensi
tydi
ff
erencesubf
ract
ion.Ther
e
ar
etwomaj
ort
ypesofspher
icalhi
ghdensi
tyl
i
popr
otei
nbasedondensi
ty
di
ff
erence:HDL2 (
1.063t
o1.125g/
mL)andHDL3(
1.25t
o1.
21g/
mL)
.HDL2
par
ti
clesar
elar
ger
,lessdense,
andr
icheri
nli
pidt
hanHDL3andmaybemor
e
ef
fi
cienti
nthedel
i
ver
yofl
i
pidst
othel
i
ver(
Bishopetal
,2018)
.
Ut
tra and hi
steam i
n 2011 st
udi
ed and det
ermi
ne t
he f
requency of
hy
per
li
pidemi
ain-
pat
ientwi
thdi
abet
esmel
l
ituswasconduct
edatcombi
ned
mi
l
itar
yhospi
tal
andl
i
quat
euni
ver
sit
yhospi
tal
.Dur
ingsexmont
hst
udyper
iod
wher
e100pat
ient(
72%mal
esand28%f
emal
e)88pat
ienthadt
ype2and12
pat
ienthadt
ype1.(
58%)pat
ientoft
ype1and(
74%)pat
ientoft
ype2wer
e
f
oundt
obehy
per
li
pidemi
a.(
lowHDLi
n08(
11%)
.
HaniM Mohamedandhi
steam i
n2019st
udi
edt
heev
aluat
ionofser
um l
i
pid
pr
ofi
l
e,cr
eat
ini
neandgl
ycat
edhemogl
obi
n(HbA1c%)i
nSudanesepat
ient
wi
tht
ype2 di
abet
esmel
l
itusassoci
ated wi
th obesi
tywasconduct
ed at
Khar
toum,Omdur
man and Khar
toum Nor
th hospi
tal
sin Khar
toum st
ate,
Sudan.Thet
estgr
oupwascompar
ewi
thacont
rolgr
oup.Wher
east
hemean
oft
heser
um l
evel
sofHDLoft
het
estgr
oupshowedasi
gni
fi
cantr
educt
ion
whencompar
ewi
thcont
rol
group.
St
udydonebyMeenuandot
her
sin2016i
nIndi
atodet
ectt
hecor
rel
ati
on
bet
weenHbA1Cv
aluesandl
i
pidpr
ofi
l
einTy
pe2Di
abet
esmel
l
itusf
oundt
hat
HbA1C l
evelcanbeusedasgoodpar
amet
erf
orpr
edi
cti
ngt
hel
i
pidpr
ofi
l
eof
bot
hmal
eandf
emal
edi
abet
icpat
ient
s.
St
udydoneby Ozougwu,
J,andot
heri
n2013 Ni
ger
iat
odet
ect The
pat
hogenesi
sandpat
hophy
siol
ogyoft
ype1andt
ype2di
abet
esmel
l
itus
f
oundt
hat Ty
pe1di
abet
esi
sther
esul
tofanaut
oimmuner
eact
iont
o
pr
otei
nsoft
hei
slet
scel
l
soft
hepancr
easwhi
l
ety
pe2di
abet
esi
scausedby
acombi
nat
ionofgenet
icf
act
orsr
elat
edt
oimpai
redi
nsul
i
nsecr
eti
on,i
nsul
i
n
r
esi
stanceandenv
ironment
alf
act
orssuchasobesi
ty,ov
ereat
ing,l
ackof
exer
ciseandst
ress,
aswel
lasagi
ng.

1.
2.Just
if
icat
ionandi
dent
if
icat
ion:

Thegl
obalf
igur
eofpeopl
esuf
fer
ingf
rom cur
rentest
imat
eof415mi
l
li
ont
o
642mi
l
li
onby2040.
Wit
hani
ncr
easi
ngi
nci
dencewor
ldwi
de,
diabet
esmel
l
itus
wi
l
lbeal
i
kel
yleadi
ngcausemor
bidi
tyandmor
tal
i
tyi
nthef
utur
e,i
tiswel
l
est
abl
i
shed t
hatdy
sli
pidemi
ais a maj
orr
isk f
act
orf
ormacr
ovascul
ar
compl
i
cat
ioni
npat
ientwi
tht
ype-
2di
abet
esmel
l
itus(
T2DM)
ANDaf
fect
s10%-
73% oft
hispopul
ati
on.
HDLl
evel
sanddi
abet
esr
iskr
ecentst
udi
eshav
e
i
ndi
cat
edt
hatchol
est
erolHDLmaydi
rect
lyal
tergl
ucosemet
abol
i
sm .
Indeed
,
HDLchol
est
erolpr
omot
espancr
eat
icB-
cel
linsul
i
nsecr
eti
onandmodi
fi
es
gl
ucoseupt
akei
nskel
etalmuscl
easshowni
ndi
ff
erentexper
iment
aland
humanset
ti
ngs.
Ther
efor
e,l
owl
evelofHDLchol
est
erolhasbeensuggest
ed
t
obeassoci
atedwi
thhi
gherr
iskoft
ype2di
abet
esi
nepi
demi
ologi
cal
studi
es.
Somest
udi
esdemonst
rat
edt
her
elat
ionshi
pbet
weenHDLpar
ti
clesandl
ower
r
iskoft
ype2di
abet
es.

1.
3.Obj
ect
ives:
1.
3.1Gener
alobj
ect
ive:
To est
imat
ehi
gh-
densi
tyl
i
popr
otei
nin cont
roland uncont
rol
l
ed di
abet
es
mel
l
itusi
nWadMedani
,Gezi
raSt
ate,
Sudan(
2019-2020)
.
1.
3.2Speci
fi
cobj
ect
ive
1.
3.2.
1Tomeasur
ehemogl
obi
nA1Ci
ndi
abet
icpat
ient
.
1.
3.2.
2 To measur
e hi
gh-
densi
tyl
i
popr
otei
nin cont
roland uncont
rol
l
ed
di
abet
es mel
l
itus.
1.
3.2.
3 To cor
rel
ate hi
gh-
densi
tyl
i
popr
otei
n wi
th hemogl
obi
n A1C and
dur
ati
onofdi
abet
es.
1.
3.2.
4Tocompar
eser
um hi
gh-
densi
tyl
i
popr
otei
nbet
weencont
rol
l
edand
uncont
rol
l
eddi
abet
esmel
l
itus.
 Chapt
erTwo
2.Li
ter
atur
eRev
iew
2.
1Di
abet
esmel
li
tus:
Thet
erm di
abet
esdescr
ibesagr
oupofmet
abol
i
cdi
sor
der
schar
act
eri
zed
andi
dent
if
iedbyt
hepr
esenceofhy
per
gly
caemi
aint
heabsenceoft
reat
ment
.
The het
erogeneous aet
io-
pat
hol
ogyi
ncl
udes def
ect
sini
nsul
i
n secr
eti
on,
i
nsul
i
nact
ion,orbot
h,anddi
stur
bancesofcar
bohy
drat
e,f
atandpr
otei
n
met
abol
i
sm.Thel
ong-
ter
m speci
fi
cef
fect
sofdi
abet
esi
ncl
uder
eti
nopat
hy,
nephr
opat
hyandneur
opat
hy,
among
ot
hercompl
i
cat
ions.Peopl
ewi
thdi
abet
esar
eal
soati
ncr
easedr
iskofot
her
di
seases i
ncl
udi
ng hear
t,per
ipher
alar
ter
ialand cer
ebr
ovascul
ardi
sease,
obesi
ty,cat
aract
s,er
ect
il
edy
sfunct
ion,andnonal
cohol
i
cfat
tyl
i
verdi
sease.
They ar
e al
so ati
ncr
eased r
isk ofsome i
nfect
ious di
seases,such as
t
uber
cul
osi
s..
(WHO,
2019)
.
2.
1.1Cl
assi
fi
cat
ionofdi
abet
esmel
li
tus:
Di
abet
es compr
ises many di
sor
der
s char
act
eri
zed by hy
per
gly
caemi
a.
Accor
dingt
othecur
rentcl
assi
fi
cat
iont
her
ear
etwomaj
ort
ypes:t
ype1
di
abet
es(
T1DM)andt
ype2di
abet
es(
T2DM)
.Thedi
sti
nct
ionbet
weent
he
t
wot
ypeshashi
stor
ical
l
ybeenbasedonageatonset
,degr
eeofl
ossofβcel
l
f
unct
ion,degr
ee ofi
nsul
i
nresi
stance,pr
esence ofdi
abet
es-
associ
ated
aut
oant
ibodi
es,andr
equi
rementf
ori
nsul
i
ntr
eat
mentf
orsur
viv
al.Howev
er,
none of t
hese char
act
eri
sti
cs unequi
vocal
l
y di
sti
ngui
shes one t
ype of
di
abet
esf
rom t
heot
her
,noraccount
sfort
heent
ir
espect
rum ofdi
abet
es
phenot
ypes.
(WHO,
2019)
.
2.
1.1.
1Ty
pe1di
abet
es:
Mal
esandf
emal
esar
eequal
l
yaf
fect
ed.Despi
teT1DM occur
ri
ngf
requent
lyi
n
chi
l
dhood,onsetcanoccuri
nadul
tsand84%ofpeopl
eli
vi
ngwi
thT1DM ar
e
adul
ts.
Di
sti
ngui
shi
ng T1DM and T2DM i
n adul
ts can be chal
l
engi
ng, and
mi
scl
assi
fyi
ng
T1DM asT2DM andv
icev
ersamayi
mpactest
imat
esofpr
eval
enceand
i
nci
dence.Ar
ecentst
udyappl
i
edaT1DM genet
icr
iskscor
etoi
ndi
vi
dual
sof
Eur
opean descentt
aki
ng par
tint
he UK’
s Bi
obank r
esear
ch pr
ojectand
concl
uded t
hat42% ofT1DM occur
red af
tert
he age of30 y
ear
s,and
account
edf
or4%ofal
lcasesofdi
abet
esdi
agnosedbet
weent
heagesof31
and60y
ear
s.Thecl
i
nicalchar
act
eri
sti
csoft
hesei
ndi
vi
dual
sincl
udedal
ower
bodymassi
ndex,
useofi
nsul
i
nwi
thi
n12mont
hsofdi
agnosi
s,andi
ncr
eased
r
iskofdi
abet
icket
oaci
dosi
s.
Ther
ateofβ-
cel
ldest
ruct
ioni
srapi
dinsomei
ndi
vi
dual
sandsl
owi
not
her
s.
Ther
api
dlypr
ogr
essi
vef
orm ofT1DM i
scommonl
yobser
vedi
nchi
l
drenbut
mayal
sooccuri
nadul
ts.Somepat
ient
s,par
ti
cul
arl
ychi
l
drenandadol
escent
s,
maypr
esentwi
thket
oaci
dosi
sast
hef
ir
stmani
fest
ati
onoft
hedi
sease.
Ot
her
smayhav
emodesthy
per
gly
caemi
athatcanr
api
dlychanget
osev
ere
hy
per
gly
caemi
aandket
oaci
dosi
sint
hepr
esenceofi
nfect
ionorot
herst
ress.
St
il
lot
her
s,par
ti
cul
arl
yadul
ts,
mayr
etai
n
r
esi
dualβ-
cel
lfunct
ionsuf
fi
cientt
opr
eventket
oaci
dosi
sformanyy
ear
s.At
t
het
imeofcl
assi
calcl
i
nicalpr
esent
ati
onwi
thT1DM,t
her
eisl
i
ttl
eorno
i
nsul
i
nsecr
eti
onasmani
fest
edbyl
oworundet
ect
abl
elev
elsofC-
pept
idei
n
bl
oodorur
ine.Thepr
esenceofobesi
tyi
npeopl
ewi
thT1DM par
all
elst
he
i
ncr
easeofobesi
tyi
nthegener
alpopul
ati
on.Bet
ween70%and90%ofpeopl
e
wi
thT1DM atdi
agnosi
shav
eev
idenceofani
mmune-
medi
atedpr
ocesswi
th
β-
cel
laut
oant
ibodi
es agai
nstgl
utami
c aci
d decar
boxy
lase (
GAD65)
,isl
et
ant
igen-
2(I
A-2)
,ZnT8t
ranspor
terori
nsul
i
n,andassoci
ati
onswi
thgenes
cont
rol
l
ingi
mmuner
esponses.I
npopul
ati
onsofEur
opeandescent
,mostof
t
he genet
ic associ
ati
ons ar
e wi
th HLA DQ8 and DQ2.The speci
fi
c
pat
hogenesi
sint
hosewi
thouti
mmunef
eat
uresi
suncl
ear,al
thoughsome
mayhav
emonogeni
cfor
msofdi
abet
es.Theset
wogr
oupsofT1DM hav
e
pr
evi
ousl
ybeenr
efer
red t
o ast
ype1A (
aut
oimmune)and t
ype1B (
non-
i
mmune)di
abet
esbutt
hist
ermi
nol
ogyi
snotf
requent
lyusednori
sitcl
i
nical
l
y
hel
pful
.Ful
minantt
ype1di
abet
esi
saf
orm ofacut
eonsetT1DM i
nadul
ts
mai
nlyr
epor
tedi
nEastAsi
a.I
taccount
sforappr
oxi
mat
ely20% ofacut
e-
onsetT1DM i
nJapanand7%i
nKor
ea.I
tisal
socommoni
nChi
nabutr
arei
n
peopl
eofEur
opeandescent
.Themaj
orcl
i
nicalchar
act
eri
sti
csoff
ulmi
nant
t
ype1di
abet
esi
ncl
udeabr
uptonset
;ver
yshor
tdur
ati
on(
usual
l
ylesst
han1
week)ofhy
per
gly
caemi
csy
mpt
oms;v
irt
ual
l
ynoC-
pept
idesecr
eti
onatt
he
t
imeofdi
agnosi
s;ket
oaci
dosi
satt
het
imeofdi
agnosi
s;most
lynegat
ivef
or
i
slet
-r
elat
ed aut
oant
ibodi
es;i
ncr
eased ser
um pancr
eat
ic enzy
me l
evel
s;
f
requentf
lu-
li
keandgast
roi
ntest
inalsy
mpt
omsj
ustbef
oret
hedi
seaseonset
.
Cel
l
ulari
nfi
l
trat
ion ofmacr
ophages and T cel
l
sint
oisl
ets suggest
s an
accel
erat
ed i
mmune r
esponse t
o v
irusi
nfect
ed i
slet cel
l
s and r
api
d
dest
ruct
ionofβ-
cel
l
s.Measur
ingi
sletaut
oant
ibodi
esr
emai
nsi
mpor
tantt
o
r
esear
chasi
tcanhel
pshedl
i
ghtont
heaet
iol
ogyandpat
hogenesi
sofT1DM .
Whi
l
emeasur
ingi
sletaut
oant
ibodi
eshasl
i
mit
edv
aluei
ncl
i
nicalpr
act
ice,i
n
cl
assi
calT1DM i
tmayhav
ear
olewhent
her
eisuncer
tai
ntyast
owhet
hera
per
sonhasT1DM orT2DM.Howev
er,t
hedeci
siont
ousei
nsul
i
nshoul
dnot
r
elyont
hepr
esenceofsuchmar
ker
s,butr
atheront
hecl
i
nicalneed..
(WHO,
2019)
.
2.
1.1.
2Ty
pe2di
abet
esmel
li
tus:
T2DM account
sforbet
ween 90% and 95% ofdi
abet
es,wi
th hi
ghest
pr
opor
ti
onsi
nlow-andmi
ddl
eincomecount
ri
es.I
tisacommonandser
ious
gl
obalheal
thpr
obl
em t
hathasev
olv
edi
nassoci
ati
onwi
thr
api
dcul
tur
al,
economi
candsoci
alchanges,agei
ngpopul
ati
ons,i
ncr
easi
ngandunpl
anned
ur
bani
zat
ion,di
etar
y changes such as i
ncr
eased consumpt
ion ofhi
ghl
y
pr
ocessedf
oodsandsugar
sweet
enedbev
erages,obesi
ty,r
educedphy
sical
act
ivi
ty,unheal
thyl
i
fest
yleandbehav
iour
alpat
ter
ns,f
etalmal
nut
ri
ti
on,and
i
ncr
easi
ngf
etalexposur
etohy
per
gly
caemi
adur
ingpr
egnancy
.T2DM i
smost
commoni
nadul
ts,butani
ncr
easi
ngnumberofchi
l
drenandadol
escent
sar
e
al
soaf
fect
ed.
β-cel
ldy
sfunct
ioni
srequi
redt
odev
elopT2DM.Manywi
th
T2DM hav
erel
ati
vei
nsul
i
ndef
ici
encyandear
lyi
nthedi
seaseabsol
utei
nsul
i
n
l
evel
sincr
easewi
thr
esi
stancet
otheact
ionofi
nsul
i
n.Mostpeopl
ewi
th
T2DM ar
eov
erwei
ghtorobese,whi
chei
thercausesoraggr
avat
esi
nsul
i
n
r
esi
stance.Manyoft
hosewhoar
enotobesebyBMIcr
it
eri
ahav
eahi
gher
pr
opor
ti
onofbodyf
atdi
str
ibut
edpr
edomi
nant
lyi
ntheabdomi
nalr
egi
on,
i
ndi
cat
ingv
iscer
aladi
posi
tycompar
edt
opeopl
ewi
thoutdi
abet
es.Howev
er,
i
nsomepopul
ati
ons,
suchasAsi
ans,
β-cel
ldy
sfunct
ionappear
stobeamor
e
not
abl
epr
omi
nentt
hani
npopul
ati
onsofEur
opeandescent.Thi
sisal
so
obser
vedi
nthi
nnerpeopl
efr
om l
ow-andmi
ddl
e-i
ncomecount
ri
essuchas
I
ndi
a,andamongpeopl
eofI
ndi
andescentl
i
vingi
nhi
gh-
incomecount
ri
es.
Formostpeopl
ewi
thT2DM,i
nsul
i
ntr
eat
menti
snotr
equi
redf
orsur
viv
albut
mayber
equi
redt
olowerbl
oodgl
ucoset
oav
ertchr
oni
ccompl
i
cat
ions.T2DM
of
tenr
emai
nsundi
agnosedf
ormanyy
ear
sbecauset
hehy
per
gly
caemi
aisnot
sev
ereenought
opr
ovokenot
iceabl
esy
mpt
omsofdi
abet
es.Nev
ert
hel
ess,
t
hese peopl
e ar
e at i
ncr
eased r
isk of dev
elopi
ng macr
ovascul
ar and
mi
crov
ascul
arcompl
i
cat
ions.
Compl
i
cat
ionsar
eapar
ti
cul
arpr
obl
em i
nyoung-
onsetT2DM –i
ncr
easi
ngl
y
r
ecogni
zedasasev
erephenot
ypeofdi
abet
esandassoci
atedwi
thgr
eat
er
mor
tal
i
tyr
ates,mor
ecompl
i
cat
ions,andunf
avor
abl
ecar
diov
ascul
ardi
sease
r
iskf
act
orswhencompar
edt
oT1DM ofsi
mil
ardur
ati
on.I
naddi
ti
on,t
he
r
esponset
o or
albl
ood gl
ucosemedi
cat
ionsi
sof
ten pooramong y
oung
peopl
ewi
thdi
abet
es.Manyf
act
orsi
ncr
easet
her
iskofdev
elopi
ngT2DM
i
ncl
udi
ng age,obesi
ty,unheal
thyl
i
fest
ylesand pr
iorgest
ati
onaldi
abet
es
(
GDM)
.Thef
requencyofT2DM al
sov
ari
esbet
weendi
ff
erentr
aci
alandet
hni
c
subgr
oups,especi
all
yiny
oungandmi
ddl
e-agedpeopl
e.Ther
ear
epar
ti
cul
ar
popul
ati
onst
hathav
eahi
gheroccur
renceoft
ype2di
abet
es,f
orexampl
e
Nat
iveAmer
icans,Paci
fi
cIsl
ander
s,andpopul
ati
onsi
ntheMi
ddl
eEastand
Sout
hAsi
a.I
tisal
soof
tenassoci
atedwi
thst
rongf
ami
l
ial
,li
kel
ygenet
icor
epi
genet
icpr
edi
sposi
ti
on.Howev
er,t
hegenet
icsofT2DM ar
ecompl
exand
notcl
ear
lydef
ined,t
hough st
udi
es suggestt
hatsome common genet
ic
v
ari
ant
s ofT2DM occuramong many et
hni
c gr
oups and popul
ati
ons .
Ket
oaci
dosi
sisi
nfr
equenti
n T2DM butwhen seen i
tusual
l
y ar
ises i
n
associ
ati
on wi
th t
he st
ress of anot
her i
l
lness such as i
nfect
ion .
Hy
per
osmol
arcomamayoccur
,par
ti
cul
arl
yinel
der
lypeopl
e.Thespeci
fi
c
aet
iol
ogi
es ofT2DM ar
e st
il
luncl
ear
,and l
i
kel
yref
lectsev
eraldi
ff
erent
mechani
sms..
(WHO,
2019)
.

2.
1.2Di
agnosi
sofdi
abet
esmel
li
tus:
Fourdi
agnost
ict
est
sfordi
abet
es ar
e cur
rent
lyr
ecommended,i
ncl
udi
ng
measur
ementoff
ast
ing pl
asma gl
ucose;2-
hour(
2-h)post
-l
oad pl
asma
gl
ucoseaf
tera75gor
algl
ucoset
oler
ancet
est(
OGTT)
;HbA1c;
andar
andom
bl
oodgl
ucosei
nthepr
esenceofsi
gnsandsy
mpt
omsofdi
abet
es.Peopl
e
wi
thf
ast
ingpl
asmagl
ucosev
aluesof≥7.
0mmol
/L(
126mg/
dl)
,2-
hpost
-
l
oad pl
asma gl
ucose ≥ 11.
1 mmol
/L(
200 mg/
dl)
),HbA1c ≥ 6.
5% (
48
mmol
/mol
);orar
andom bl
oodgl
ucose≥11.
1mmol
/L(
200mg/
dl
)int
hepr
esenceofsi
gnsandsy
mpt
omsar
econsi
der
edt
ohav
edi
abet
es.
I
fel
evat
ed v
alues ar
e det
ect
ed i
n asy
mpt
omat
ic peopl
e,r
epeatt
est
ing,
pr
efer
abl
ywi
tht
hesamet
est
,isr
ecommendedassoonaspr
act
icabl
eona
subsequentdayt
o conf
ir
m t
he di
agnosi
s.A di
agnosi
s ofdi
abet
es has
i
mpor
tanti
mpl
i
cat
ions f
ori
ndi
vi
dual
s,notonl
yfort
hei
rheal
th,butal
so
becauseoft
hepot
ent
ialst
igmat
hatadi
abet
esdi
agnosi
scanbr
ingmay
af
fectt
hei
rempl
oyment
,heal
th and l
i
fei
nsur
ance,dr
ivi
ng st
atus,soci
al
oppor
tuni
ti
es, and car
ry ot
her cul
tur
al, et
hical and human r
ight
s
consequences..
(WHO,
2019)
.
2.
1.3Pat
hogenesi
sofdi
abet
esmel
li
tus:
Ty
pe1di
abet
esmel
l
itusi
sachr
oni
caut
oimmunedi
seaseassoci
atedwi
th
sel
ect
ivedest
ruct
ionofi
nsul
i
n-pr
oduci
ngpancr
eat
icβ-
cel
l
s.Theonsetof
cl
i
nicaldi
seaser
epr
esent
stheendst
ageofβ-
cel
ldest
ruct
ionl
eadi
ngt
oty
pe
1di
abet
esmel
l
itus.Al
HomsiandLuki
c(1992)expl
ainedt
hatsev
eralf
eat
ures
char
act
eri
ze t
ype 1 di
abet
es mel
l
itus as an aut
oimmune di
sease.Under
nor
mal phy
siol
ogi
cal condi
ti
ons, pl
asma gl
ucose concent
rat
ions ar
e
mai
ntai
nedwi
thi
nanar
row r
ange,despi
tewi
def
luct
uat
ionsi
nsuppl
yand
demand,t
hroughat
ight
lyr
egul
atedanddy
nami
cint
eract
ionbet
weent
issue
sensi
ti
vi
tyt
oinsul
i
n(especi
all
yinl
i
ver
)and i
nsul
i
n secr
eti
on.I
nty
pe 2
di
abet
est
hesemechani
smsbr
eakdown,wi
tht
heconsequencet
hatt
het
wo
mai
npat
hol
ogi
caldef
ect
sint
ype2di
abet
esar
eimpai
redi
nsul
i
nsecr
eti
on
t
hroughady
sfunct
ionoft
hepancr
eat
icβ-
cel
l
,andi
mpai
redi
nsul
i
nact
ion
t
hroughi
nsul
i
nresi
st Ozougwuetal
ance( ,2013)
.
2.
1.4Sy
mpt
oms:
Thechar
act
eri
sti
ccl
i
nicalpr
esent
ati
on i
swi
tht
hir
st,pol
yur
ia,bl
urr
ing of
v
isi
onandwei
ghtl
oss.Thi
scanl
eadt
oket
oaci
dosi
sorhy
per
osmol
arnon-
ket
oti
ccoma.Of
ten,sy
mpt
omsar
emi
l
dorabsentandmi
l
dhy
per
gly
cemi
a
canper
sistf
ory
ear
swi
tht
issuedamagedev
elopi
ng,
alt
hought
heper
sonmay
bet
otal
l
yasy
mpt
omat
ic.(
Geor
geandAl
ber
ti
,2010)
.
2.
1.5compl
icat
ion:

Amongpeopl
ewi
thdi
abet
es,about15%hav
ety
pe1,whi
l
eabout85%hav
e
t
ype2.I
nty
pe1di
abet
es,t
hemaj
orr
iski
smi
crov
ascul
arcompl
i
cat
ions,
al
thoughmacr
ovascul
arcompl
i
cat
ionsar
eal
soi
ncr
eased.Thepr
imar
yri
sk
f
act
ori
shy
per
gly
caemi
a,al
thoughot
herr
iskf
act
ors,suchashy
per
tensi
on
anddy
sli
pidaemi
a,mayoccursecondar
ytouncont
rol
l
edhy
per
gly
caemi
aor
r
enaldi
sease.Compl
i
cat
ionsar
ether
efor
eusual
l
yacqui
redaf
terdi
agnosi
s.
I
ncont
rast
,ty
pe2di
abet
esi
susual
l
ypar
toft
he“
met
abol
i
csy
ndr
ome”
,whi
ch
i
sassoci
ated wi
th ot
herr
iskf
act
orsf
rom ear
lyi
nthe di
sease pr
ocess,
i
ncl
udi
ng abdomi
nalobesi
ty,hy
per
tensi
on,dy
sli
pidaemi
a,apr
othr
ombot
ic
st
ateandi
nsul
i
nresi
stance.Al
thoughmacr
ovascul
ardi
seasei
sthemaj
or
cause of mor
bidi
ty and mor
tal
i
tyi
n t
ype 2 di
abet
es,mi
crov
ascul
ar
compl
i
cat
ionsar
eof
tenpr
esentwhendi
abet
esi
sdi
agnosed,ev
eni
npeopl
e
wi
thnosy
mpt
oms.Pr
eval
encesatdi
agnosi
sar
e:r
eti
nopat
hy,about20%;
neur
opat
hy,9%;andov
ertdi
abet
icnephr
opat
hy,upt
o10%.Ty
pe2di
abet
es
i
ncr
easest
her
iskofcor
onar
yhear
tdi
seaset
wo-t
ofour
fol
dandabol
i
shest
he
pr
otect
ivenessoff
emal
esexobser
vedi
nthenon-
diabet
icpopul
ati
on.The
pr
esence of di
abet
es al
so wor
sens t
he pr
ognosi
s of cor
onar
y hear
t
di
sease.
(Bat
e,Jer
ums,
2003)

2.
1.5.
1Macr
ovascul
arcompl
icat
ion:

The cent
ralpat
hol
ogi
calmechani
sm i
n macr
ovascul
ar di
sease i
sthe
pr
o¬cess ofat
her
oscl
erosi
s,whi
ch l
eads t
o nar
rowi
ng ofar
ter
ialwal
l
s
t
hrough¬outt
he body
.At
her
oscl
erosi
sist
houghtt
oresul
tfr
om chr
oni
c
i
nfl
am¬mat
ionandi
njur
ytot
hear
ter
ialwal
lint
heper
ipher
alorcor
onar
y
v
ascul
arsy
stem.I
nresponset
oendot
hel
i
ali
njur
yandi
nfl
ammat
ion,oxi
dized
l
i
pids f
rom LDL par
ti
cles accumul
atei
nthe endot
hel
i
alwal
lofar
ter
ies.
Di
abet
esi
ncr
easest
her
iskt
hatani
ndi
vi
dualwi
l
ldev
elopcar
diov
as¬cul
ar
di
sease(
CVD)
.Al
thought
hepr
eci
semechani
smst
hroughwhi
chdi
abet
es
i
ncr
eases t
he l
i
kel
i
hood of at
her
oscl
erot
ic pl
aque f
ormat
ion ar
e not
compl
etel
ydef
ined,
theassoci
a¬t
ionbet
weent
het
woi
spr
ofound.CVDi
sthe
pr
imar
ycauseofdeat
hinpeopl
ewi
thei
thert
ype1ort
ype2di
abet
es.I
nfact
,
CVD account
sfort
hegr
eat
estcomponentofheal
thcar
eexpendi
tur
esf
or
peopl
ewi
thdi
abet
es.
(Al
ber
tiandFowl
er,
2011)
.

2.
1.5.
2Mi
crov
ascul
arcompl
icat
ion:
2.
1.5.
2.1per
ipher
alneur
opat
hy:
Di
abet
icneur
opat
hyi
srecogni
zed byt
heAmer
ican Di
abet
esAssoci
ati
on
(
ADA) as “
the pr
esence of sy
mpt
oms and si
gns of per
ipher
alner
ve
dy
sfunct
ioni
npeopl
ewi
thdi
abet
esaf
tert
heexcl
usi
onofot
hercauses.As
wi
th ot
hermi
crov
ascul
arcom¬pl
i
cat
ions,t
he r
isk ofdev
elopi
ng di
abet
ic
neur
opat
hy i
s pr
opor
ti
onal t
o bot
h t
he magni
tude and dur
ati
on of
hy
per
gly
cemi
a,andsomei
ndi
vi
dual
smaypossessgenet
icat
tri
but
est
hat
af
fectt
hei
rpr
edi
sposi
ti
on t
o dev
elop¬i
ng such compl
i
cat
ions.Per
ipher
al
neur
opat
hyi
ndi
abet
esmaymani
festi
nsev
eraldi
ff
erentf
orms,i
ncl
ud¬i
ng
sensor
y,f
ocal
/mul
ti
focal
,andaut
onomi
cneur
opat
hies.Mor
ethan80% of
amput
ati
onsoccuraf
terf
ootul
cer
ati
on ori
njur
y,whi
ch can r
esul
tfr
om
di
abet
icneur
opat
hy..
(Al
ber
tiandFowl
er,
2011)
.

2.
1.5.
2.2Di
abet
icnephr
opat
hy:
Di
abet
icnephr
opat
hyi
sthel
eadi
ngcauseofr
enalf
ail
ure.I
tisdef
inedby
pr
otei
nur
iaof>500mgi
n24hour
sint
heset
ti
ngofdi
abet
es,butt
hisi
s
pr
eceded by l
ower degr
ees of pr
otei
nur
ia,cal
l
ed “
micr
o¬al
bumi
nur
ia.
Mi
croal
bumi
nur
iai
sdef
inedasal
bumi
nexcr
eti
onof30–299mg/
24hour
s.
Wi
thout i
nter
vent
ion,di
abet
ic pat
ient
s wi
th mi
croal
bumi
nur
ia t
ypi
cal
l
y
pr
ogr
esst
o pr
otei
nur
ia and ov
ertdi
abet
icnephr
opat
hy.Thi
spr
ogr
essi
on
occur
sinbot
hty
pe1andt
ype2di
abet
es.Pat
hol
ogi
calchangest
otheki
dney
i
ncl
ude i
ncr
eased gl
o¬mer
ular basement membr
ane t
hickness,
mi
croaneur
ysm f
orma¬t
ion,mesangi
alnodul
efor
mat
ion(
Kimmel
stei
l
-Wi
l
son
bodi
es)
,andot
herchanges.Theunder
lyi
ngmech¬ani
sm ofi
njur
ymayal
so
i
nvol
vesomeoral
loft
hesamemechani
smsasdi
abet
icr
eti
nopat
hy..
(Al
ber
ti
andFowl
er,
2011)
.

2.
1.5.
2.2Ret
inopat
hy:
Dev
elopmentofdi
abet
icr
eti
nopat
hyi
npat
ient
swi
tht
ype2di
abet
eswasf
oundt
obe
r
elat
edt
obot
hthesev
eri
tyofhy
per
gly
cemi
aandt
hepr
esenceofhy
per
tensi
oni
nthe
U.
K.Pr
ospect
iveDi
abet
esSt
udy(
UKPDS)
,andmostpat
ient
swi
tht
ype1di
abet
es
dev
elopev
idenceofr
eti
nopat
hywi
thi
n20y
ear
sofdi
agnosi
s.Ret
inopat
hymaybegi
n
t
odev
elopasear
lyas7y
ear
sbef
oret
hedi
agnosi
sofdi
abet
esi
npat
ient
swi
tht
ype2
di
abet
es. I
tisi
mpor
tantt
ochar
act
eri
zedbyt
hef
ormat
ionofnewbl
oodv
essel
son
t
hesur
faceoft
her
eti
naandcanl
eadt
ovi
tr
eoushemor
rhage.Whi
tear
easont
he
r
eti
na(
“cot
tonwoolspot
s”)canbeasi
gnofi
mpendi
ngpr
oli
fer
ati
ver
eti
nopat
hy.I
f
pr
oli
fer
ati
on cont
in¬ues,bl
i
ndness can occurt
hrough v
itr
eous hemor
rhage and
t
ract
ionr
eti
nal
det ..
achment (Al
ber
tiandFowl
er,
2011)
.

2.
2Li
popr
otei
n:
Li
popr
otei
nsconst
it
utet
hebody
’s.Li
ket
hegr
eatoi
ltanker
s,chy
lomi
crons
ar
elar
ge,l
i
pid-
ri
cht
ranspor
tvessel
sthatf
err
ydi
etar
ytr
igl
ycer
ides,t
hemai
n
oi
lint
hebody
,thr
oughoutt
heci
rcul
ator
ysy
stem t
ocel
l
s,f
inal
l
ydocki
ngat
t
hel
i
veraschy
lomi
cronr
emnant
s.Thev
eryl
ow densi
tyl
i
popr
otei
ns(
VLDL)
ar
eli
ket
ankert
rucks,car
ryi
ngt
ri
gly
cer
idesassembl
edi
nthel
i
vert
ocel
l
sfor
ener
gyneedsorst
orageasf
at.Thel
ow-
densi
tyl
i
popr
otei
ns(
LDL)
,ri
chi
n
chol
est
erol
,ar
ethenear
lyempt
ytanker
sthatdel
i
verchol
est
erolt
oper
ipher
al
cel
l
sandl
i
veraf
tert
het
ri
gly
cer
ideshav
ebeenof
f-
loaded.Thehi
gh-
densi
ty
l
i
popr
otei
ns(
HDL)ar
ethecl
eanupcr
ew,gat
her
ingupexcesschol
est
erolf
or
t
ranspor
tbackt
othel
i
ver
.Chol
est
eroli
susedbyt
hebodyf
orsuchusef
ul
f
unct
ionsasf
aci
l
itat
ingt
ri
gly
cer
idet
ranspor
tbyl
i
popr
otei
ns,f
ormai
ntai
ning
t
henor
malst
ruct
ureandi
ntegr
it
yofcel
lmembr
anes,andasapr
ecur
sorf
or
st
eroi
dhor
monesy
nthesi
s,butwheni
nexcess,i
tcanl
eadt
ocar
diov
ascul
ar
di
sease.Li
pidsandl
i
popr
otei
ns,whi
char
ecent
ralt
otheener
gymet
abol
i
sm
oft
hebody
,hav
ebecomei
ncr
easi
ngl
yimpor
tanti
ncl
i
nicalpr
act
ice,pr
imar
il
y
becauseoft
hei
rassoci
ati
onwi
thcor
onar
yhear
tdi
sease(
CHD)
.Numer
ous
epi
demi
ologi
cst
udi
eshav
edemonst
rat
edt
hat
,especi
all
yinaf
fl
uentcount
ri
es
wi
thhi
ghf
atconsumpt
ion,
ther
eisacl
earassoci
ati
onbet
weent
hebl
oodl
i
pid
l
evel
sandt
hedev
elopmentofat
her
oscl
erosi
s.(
Bishopetal
,2018)
.
2.
2.1Hi
ghdensi
tyl
ipopr
otei
n:
HDL,t
hesmal
l
estandmostdensel
i
popr
otei
npar
ti
cle,i
ssy
nthesi
zedbybot
h
t
hel
i
verandi
ntest
ine.HDLcanexi
stasei
therdi
sk-
shapedpar
ti
clesor
,mor
e
commonl
y, spher
ical par
ti
cles. Di
scoi
dal HDL t
ypi
cal
l
y cont
ains t
wo
mol
ecul
esofapoA-
I,whi
chf
orm ar
ingar
oundacent
rall
i
pidbi
l
ayerof
phosphol
i
pidandchol
est
erol
.Di
scoi
dalHDLi
sbel
i
evedt
orepr
esentnascent
ornewl
ysecr
etedHDLandi
sthemostact
ivef
orm i
nremov
ing excess
chol
est
erolf
rom per
ipher
alcel
l
s.Theabi
l
ityofHDLt
oremov
echol
est
erol
f
rom cel
l
s,cal
l
ed r
ever
se chol
est
erolt
ranspor
t,i
s one of t
he mai
n
mechani
smspr
oposedt
oexpl
aint
heant
iat
her
ogeni
cpr
oper
tyofHDL.When
di
scoi
dal HDL has acqui
red addi
ti
onal l
i
pid, chol
est
ery
l est
ers and
t
ri
gly
cer
ides f
orm a cor
eregi
on bet
ween i
ts phosphol
i
pid bi
l
ayer
,whi
ch
t
ransf
ormsdi
scoi
dalHDLi
ntospher
icalHDL.HDLi
shi
ghl
yhet
erogeneous
separ
abl
eint
oasmanyas13or14di
ff
erentsubf
ract
ions.Ther
ear
etwo
maj
ort
ypesofspher
icalHDLbasedondensi
tydi
ff
erences:HDL2andHDL3.
HDL2par
ti
clesar
elar
geri
nsi
zeandr
icheri
nli
pidt
hanHDL3andmayr
efl
ect
bet
teref
fi
ciencyi
ndel
i
ver
ingl
i
pidst
othel
i
ver
..(
Bishopetal
,2018)
.
2.
2.2Dy
sli
pidemi
aindi
abet
icpat
ient
:
Pat
ient
swi
tht
ype-
2di
abet
eshav
eincr
easedr
iskofcar
diov
ascul
ardi
sease
associ
ated wi
th at
her
ogeni
c dy
sli
pidaemi
a. Cor
onar
y ar
ter
y di
sease,
especi
all
y my
ocar
diali
nfar
cti
on i
sthe l
eadi
ng cause ofmor
bidi
ty and
mor
tal
i
tywor
ldwi
de.Hy
per
gly
caemi
aandat
her
oscl
erosi
sar
erel
atedi
nty
pe-
2di
abet
es.Per
sist
enthy
per
gly
caemi
acausesgl
ycosy
lat
ionofal
lpr
otei
ns,
especi
all
ycol
l
agencr
ossl
i
nki
ngandmat
ri
xpr
otei
nsofar
ter
ialwal
l
.Thi
s
ev
ent
ual
l
y causes endot
hel
i
alcel
ldy
sfunct
ion,cont
ri
but
ing f
urt
her t
o
at
her
oscl
erosi
s.Thepr
eval
enceofdy
sli
pidemi
ain
di
abet
esmel
l
itusi
s95%.Thedy
sli
pidemi
aisamaj
orr
iskf
act
orf
orcor
onar
y
hear
tdi
sease(
CHD)
.Thecar
diov
ascul
ardi
seasei
sacauseofmor
bidi
tyand
mor
tal
i
tyi
n pat
ient
s wi
th di
abet
es mel
l
itus because ofdi
stur
bance i
n
l
i
popr
otei
nsi
.e.ser
um t
ri
gly
cer
ides(
TC)69%,ser
um chol
est
erol56.6%,l
ow-
densi
tyl
i
popr
otei
n chol
est
erol(
LDL) 77% and hi
gh densi
tyl
i
popr
otei
n
chol
est
erol(
HDL)71% .Ther
ati
onal
eoft
hisst
udywast
odet
ectt
hel
i
pid
abnor
mal
i
ty i
n di
abet
ic pat
ient
s. Ear
ly det
ect
ion and t
reat
ment of
hy
per
li
pidemi
ain di
abet
es mel
l
itus can pr
eventt
he pr
ogr
essi
on ofl
i
pid
abnor
mal
i
tiesandmi
nimi
zet
her
iskf
orat
her
ogeni
ccar
diov
ascul
ardi
sor
der
andcer
ebr
ovascul
aracci
dent
.(Ut
tra etal
,2011)
.
2.
3Hemogl
obi
nA1C:
Gl
ycosy
lat
edhemogl
obi
nist
het
erm usedt
odescr
ibet
hef
ormat
ionofa
hemogl
obi
ncompoundpr
oducedwhengl
ucose(
areduci
ngsugar
)react
swi
th
t
heami
nogr
oupofhemogl
obi
n(apr
otei
n).Thegl
ucosemol
ecul
eat
taches
nonenzy
mat
ical
l
ytot
hehemogl
obi
nmol
ecul
etof
orm aket
oami
ne.Ther
ate
off
ormat
ioni
sdi
rect
lypr
opor
ti
onalt
othepl
asmagl
ucoseconcent
rat
ions.
Because t
he av
erage r
ed bl
ood cel
lli
ves appr
oxi
mat
ely 120 day
s,t
he
gl
ycosy
lat
edhemogl
obi
nlev
elatanyonet
imer
efl
ect
stheav
eragebl
ood
gl
ucosel
evelov
ert
hepr
evi
ous2t
o3mont
hs.Ther
efor
e,measur
ingt
he
gl
ycosy
lat
edhemogl
obi
npr
ovi
dest
hecl
i
nici
anwi
that
ime-
aver
agedpi
ctur
e
oft
hepat
ient
’sbl
oodgl
ucoseconcent
rat
ionov
ert
hepast3mont
hs.
HbA1ct
hemostcommonl
ydet
ect
edgl
ycosy
lat
edhemogl
obi
n,i
sagl
ucose
mol
ecul
eat
tachedt
ooneorbot
hN-
ter
minalv
ali
nesoft
hebet
a-pol
ypept
ide
chai
nsofnor
maladul
themogl
obi
n.HbA1ci
samor
erel
i
abl
emet
hodof
moni
tor
ingl
ong-
ter
m di
abet
escont
rolt
hanr
andom pl
asmagl
ucose.Nor
mal
v
aluer
ange4.
0%t
o6.
0%.(
Bishopetal
,2018)
.
Gl
ycat
ed hemogl
obi
n(HbA1c)i
srout
inel
y used as a di
agnost
ict
oolf
or
measur
ingl
ongt
erm gl
ycemi
ccont
rol
.Inaccor
dancewi
thi
tsf
unct
ionasan
i
ndi
cat
orf
ort
hemeanbl
oodgl
ucosel
evel
,HbA1cpr
edi
ctst
her
iskf
ort
he
dev
elopmentofdi
abet
iccompl
i
cat
ioni
ndi
abet
espat
ient
s.TheUKPDSst
udy
has shown t
hati
n pat
ient
s wi
tht
ype 2 di
abet
es,t
he r
isk of di
abet
ic
compl
i
cat
ions wer
e st
rongl
y associ
ated wi
th pr
evi
ous hy
per
gly
cemi
a.
Gl
ycemi
ccont
rolwi
thdecr
easedl
evelofHbA1ci
sli
kel
ytor
educet
her
iskof
compl
i
cat
ions.Est
imat
edr
iskofCar
dioVascul
arDi
seases(
CVD)hasshown
t
obei
ncr
easedby18% f
oreach1% i
ncr
easei
nabsol
uteHbA1cv
aluei
n
di
abet
ic4.Ev
eni
nnondi
abet
iccaseswi
thHbA1cl
evel
swi
thi
nnor
malr
ange,
posi
ti
ve r
elat
ionshi
p bet
ween HbA1c and CVD has been
demonst
rat (Meenue
ed. tal
,2016)
.
 Chapt
erThr
ee
3.
Mat
eri
alsandMet
hod
3.
1Met
hdoi
ogy

3.
1.1St
udydesi
gn:
Thi
siscr
osssect
ional
studyai
medt
oev
aluat
ehi
gh-
densi
tyl
i
popr
otei
nin
cont
rol
anduncont
rol
l
eddi
abet
esmel
l
itus.
3.
1.2St
udyar
ea:
The Gezi
ra st
atel
i
es bet
ween l
ati
tudes (
13-
32 and 15-
30)nor
th and
l
ongi
tudes(
22-
32and20-
34)east
.Iti
sbor
der
edbyKhar
toum St
atet
othe
nor
th,
SinnarSt
atet
othesout
h,Gadar
ifSt
atet
otheeastandWhi
teNi
l
eSt
ate
t
othewest
.Ithasanar
eaof27,
549 
km²
.Ami
xtur
eofr
acesandt
ri
besf
rom
i
nsi
de and out
side Sudan i
nhabi
ted popul
ati
on.The name comes f
rom
t
he 
Arabi
c wor
dfori
sland.
 WadMadani
 
ist
hecapi
taloft
hest
ate.TheGezi
ra
i
sawel
l
-popul
atedar
easui
tabl
eforagr
icul
tur
e.Ther
egi
onhasbenef
it
ed
f
rom t
he 
Gezi
raScheme,
apr
ogr
am t
ofost
ercot
ton 
far
mingbeguni
n1925.
3.
1.3St
udyDur
ati
on:
Thi
sst
udywasdonei
nGezi
rast
atef
rom Nov
ember2019t
oApr
il2020.
3.
1.4St
udypopul
aton:
i
Thi
s st
udy was doi
ng i
n adul
tdi
abet
ic pat
ientl
eav
ing i
n Wad Madani
accor
dingt
oincl
usi
onandexcl
usi
oncr
it
eri
a.
3.
1.6Sampl
ingandsampl
esi
ze:
TheSt
udywasr
andomi
zi
ngsampl
i
ngandcal
cul
atebyt
hisequat
ion:
n=z2*
pq/
d2
n=sampl
esi
ze
z=l
evel
ofconf
idantt
ost
andar
dnor
mal
dist
ri
but
ion
q=1-
p
p=est
imat
edpr
opor
ti
onal
ofpopul
ati
ont
hatpr
esentt
hechar
act
eri
sti
cs
d=t
oler
atedmar
ginofer
ror
3.
1.6St
udyv
ari
abl
es:
3.
1.6.
1Dependentv
ari
abl
es:
Hi
ghdensi
tyl
i
popr
otei
n.

3.
1.6.
2Independentv
ari
abl
es:
Hemogl
obi
nA1C.
Di
seasedur
ati
on.
3.
1.7St
udycr
it
eri
a:
3.
1.7.
1Incl
usi
oncr
it
eri
a:
1.
Agr
eedt
oinv
olv
eint
hest
udy
.
2.
Adul
tdi
abet
icpat
ient
.
3.
1.7.
2Excl
usi
oncr
it
eri
a:
Car
diov
ascul
ardi
sease
Smoki
ng
Li
verdi
sease
Renal
disease
Gest
ati
onal
women.
3.
1.8Dat
acol
lect
iont
ool
s:
The dat
a wascol
l
ect
ed byusi
ng a quest
ionnai
re.A quest
ionnai
re was
desi
gnedt
oincl
udeal
lneededi
nfor
mat
ion.
3.
1.9Et
hicalConsi
der
aton:
i
Et
hicalcl
ear
ancef
ort
hisst
udywasobt
ainedf
rom uni
ver
sit
yofGezi
ra.The
speci
mensandi
nfor
mat
ionwascol
l
ect
edf
rom peopl
eunderpr
ivacyand
conf
ident
ial
l
yandwasnotbeusedf
oranypur
posesr
athert
hant
hisst
udy
.
I
nfor
medconsent
swi
l
lbeobt
ainedf
rom adul
tindi
vi
dual
sbef
orespeci
men
col
l
ect
ionpr
ocedur
e.
3.
2Mat
eri
als:
Sy
ringes,
alcohol
,cot
ton,
aut
omat
icpi
pet
teandt
ips,
tour
niquet
,gl
oves,
high-
densi
tyl
i
popr
otei
nreagent
.
3.
3Met
hods:
3.
3.1Sampl
ecol
lect
ionandpr
epar
ati
on:
Af
terusi
ngofl
ocal
ant
i-
sept
icf
ort
heski
n(70%et
hanol
)af
ast
ingsampl
eof
v
enousbl
ood(
5ml
)insodi
um hepar
int
ubewi
l
lbecol
l
ectf
rom eachi
ndi
vi
dual
i
ncl
udedi
nthest
udy
.
3.
3.2Labor
ator
yanal
ysi
sandpr
ocedur
es:
Bi
osy
stem A15
 Ref
erence

Wor
ldHeal
thOr
gani
zat
ion,
(2019)
."Cl
assi
fi
cat
ionofdi
abet
esmel
l
itus"
.

1. Bi
shop,M.
L.,Fody
,E.
P.and Schoef
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