2015 J-r)tLJl (r4,) rr,Jl"..tlror(riKitr

Relationship between serum testosterone and sex hormone- binding globulin

levels and some metabolic changes in Iraqi men with type 2 diabetes mellitus

gl :+rrJl,:tttr.r1rlLLrr1jll JE lr4rrlAllrglall g4frdl jrrarc gog iiilrll2 7;ll gl g.f-Jl+ i;+rLctl il*flr.ll Jhrl Jrt i;ag{l ^:lr*i:Il Ji.{rpJl Jh.

Haleem Hamadi lssaMohammadDeportment ol Animal ResourcesCollege of Agriculture

Department of BiologtCollege of Science

University of Wasit

O-B:.".J1

dll d;.-. d ,rKJl oJli.,..i,ill ur.-.;o u# a-6)'Jt .*at Jt i-t;Jl o:r ergaJ-u:-_r$tL-llr,(SHBG) .r1."i.ll drur^JdL J.lylt ..r:tr*rtslt_r (S.Testosterone)

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";" rt-r,t, L4,r .r:Lr tu ril r:4-,lJJl ora si

. dll Li;J (BMl) i""+ll ilS _r-r.: T2DM ;r.:,--+lr Fl al,j)l d,-:L-ill d-r+ilruJ^JCtr.t"S_rtl Ut_*rSllJ qrsll drj_,.Ji-,..i-ill) rJl Ji.- d a$yt (:Jtjj.jll uP,l",i ir TC ,r.lSt dJ !:fi.+l3sll) ,',1-.'"r dJl ,J... e-d .r"tr i ( ;SSYr+ll ey-,,1l3 rgll,,-.!l_2L"cl L.F JS . (HDL-C) iltislt 4c_r J3;g-;lglt, (TG) +!Xtt d,l+J.r-,lsll

(BMl) e-"+ll ils -*:..rir ij- 5.4 t5.2 .js (Fll ;! t-..;-, .i:- 49.8 15.7;.*: ..19rll 3UrS. CJ^+ c.,rtS .i-iJl :i ..,j:Jl .y:rlj . ::i. : ,:r ; ..;tS i*lJil 4.c r.i.^I

*lSlt ;3:*:-,.;JlJ q-j+11 c,rUJ _JsIi J.I_*tt +lr*rlStl drtJ ri,". c,.,lS I -tJi sr+l| dr,ll..Jlrrll ,sJ' 18.12t28.88 :2.11*.4.49 )i;iii"ll eplt ;, t,<tr,o.+$ll glr.Jl ;-.-:

)ful"t ll elill g" +rSl3,*4+rlll $'Jl .t-.-: p:ll d .-rSY:!t .9.r:.".;lS drJ- d (

-AlL'rl ar. -$i 3i .r-l-e rJ+J 4..,'lJJ tii: !:rt-lrill ;j;ti. c,r,"l l-r.e .(11.22*9.42tt-t^-g c_fu L..JL i.F ,'5s !Jl,- L:liijl ctt-i,a ;tS Sl r;.:;yt Lj)i]Jl ,1 ..j,-.$l

ij^.,,11 ;F iJil,.j Y ;..r! fu_2tL aj^Jl .-). lJlt.J ,J+ll g;6Jl .ri-_r .rJ UJ#- n-illdlr L. ' ct LE:l :,p.-e ric .(P<0.001 ,ng/ ml 2.17 x 4.79 &b 1.87 t 3.89)(fJ. C. tu-iL SHBG dl4-^ ,gP JS+ ,-'.aiiil $i g;6J13 ij...Jl Jl 4!L;Yt+

t 33.58 d.,.lL 13"42 t 25.16):,j...J| rF.r-rt.: Y-r,.rll L: ' glij.1t pe.:l JCI tr_SJlrer Jl iil;Yt+ p:ll L: ' d tln_.rl ell$ rjSlrl .(P <0.05 .JlCl ,Jeng/ ml 13.73qlc OJ-$--.j-illJ SHBG qf t'y- ulou-ll .:ll,rA ,JK rai HDL-C

";ati,iil dlSl i:l:rJl

r 5.57 d,.tl 1.9 f 3.73 _rng/ ml 6.33 r40.7 clti. 14.93 t 30.63) orr- o.(0.01> p,;l}r*&ng/ ml 1.53

JJ

Marwa Kareem Qa.sem

2015 JYli.-Jl (riz) :-iJl i^,Ul.,r<lL5'il3

Abstract

The present study aimed to assess the interrelationship between serum total testosterone

(S.Tes) as well as sex hormone binding globulin (SHBG) and the main components of

metabolic syndrome (MetS) in type 2 diabetic men.

One hundred and sixty patients having T2DM were enrolled in this study. The following

characteristics were reported: age, gender, duration of T2DM, Body mass index (BMI) and

arterial blood pressure.. Serum hormonal profile analyses (S.I'es, SHBG and prolactin).

Serum lipid analyses (T.ch TG, HDL-C, and LDL-C).

The mean age of study subjects was 49.8 ts.l years and the mean duration of disease

was 5.4+5.2 years. Body mass index (BMI) of study group was found to be within the range

of either overweight or obese class . The means of HbAlc ratio and FSG levels were 9.4 7o

t 2.1 and 200.9 f 75.2 mg/dl respectively which indicated that our patients were in a bad

glycemic control. All components of S. lipid profile were within normal range . Serum

Testosterone and SHBG levels were within normal range but in the low values( 4.49,12.1I

,28.88+18.12 nglml respectively) while serum prolactin level was within normal range bu1

in the high values(l 1.22+9.42 ng/ml). When study analytes were compared according to the

presence of one or more metabolic syndrome characteristic then there was a significant

decrease in mean value of testosterone level between obese and non obese diabetics (

3.89+1.87 vs.4.79+2.17 ng/ ml, P < 0.001) . If hypertension was present in addition to

obesity and diabetes then SHBC level was also significantly decreased in comparison with

diabetics who were hypertensive but not obese (25.16x13.42 vs. 33.58+13.73 ng/ ml

respectively, P <0.05 ). If hypertension and obesity were present as well as lower HDL-C

;j+- lJJd;i s i*,lJJl '- ,J ( T2DM) 2 t+t a g;S-Jt .rr-:" dji i{J' d ,d,Jj-Ji-,311 tty;r,. Cfu d ..rJ-- dr"UijicliA .Jl r+J t-S fJl sr S-'ll 4+"1 ,.lJc 1!-

3ti:-.ri ul-r i+.:.r)t Lixjl .9F -i--l-i ]}Aui FIJP rr) .ij^.,J1 dr Jll"J o,l$ e)} '!cjrros-riar .5 n*c os .9 .&-6 (Fuijt Jl ,r..1u ( HDL-C ) .Fii:l-r dtl l,!.:q-..t-,!f -ltJill ir* .x ,i-^Jl c.ri .olJ.. o .rJc 'r"rttt .U-r.-.rit+ LJrll a,lP-.-t}tll3

Crr:srl: lJJ:c-JLiIl o.. C !.rsr *#-ll J:Yl kl .ti r+ , L:.,)l L-,1>o"11 .e;!t2 7At A g;S-Jt .r.--r rie ir""lsll f,JUJ"JcJL LJIJJI

34

^-.tlror(r{a+

then significant decreases in both S. SHBG and S. Tes were detected ( (30.63+14.93 vs.

40.7+ 6.33 ng/ ml and 3.73'11 .9 vs. 5.57+ I .53 ng/ ml respectively , P<0.01 ).

In conclusion; our l'2DM patients have a bad glycemic state and are characterized by a

significantly lower S. Tes mean level if they were obese. Still, the accumulation of other

main characteristics of MetS which included hypertension and lower S. HDt,- C results in

a significantly lower mean levels of both S. Tes and S. SHBG. Obesity, among the other

core characteristics of MetS, seems to have the main suppressor effect on serum

testosterone and SHBG in T2DM.

Introduction

Diabetes mellitus (DM) is a metabolic disorder characterized by chronic

hyperglycemia with disturbance of carbohydrate, fat, and protein metabolism resulting

from insulin deficiency or a defect in insulin action or a combination of both @uropean

Society of Cardiology,20'l 1). Diabetes mellitus is classified as either type I or insulin-

dependent which can be controlled only by daily injections of insulin or type 2 or non-

insulin dependent which is treated by several types of synthetic therapeutics. Type 2 DM

significantly increases the risk ofdeveloping cardiovascular diseases such as coronary heart

disease , stroke and amputation (Huang et a1.,2007). Metabolic syndrome (MetS) is defined

as an association of interrelated risk factors of metabolic origin such as obesity,

dyslipidemia and hypertension with a heightened risk for cardiovascular disease in T2DM

(Rizvan 201l, Sattar et al., 2003). The prevalence of the metabolic syndrome in patients

with type 2 diabetes mellitus varies between 70-90 o/o (Alexander,2003; lsomaa,20Ol ;

Song,2008).

Testosterone is a steroid hormone and is the primary mammalian androgen and is

produced primarily by the testes, but also in small quantities by the adrenal glands in both

males and females (Carlson, 2003). In the circulation, testosterone is bound with high

affinity to sex hormone-binding globulin (SHBC) and weakly to albumin while there is a

small fraction ofunbound or free testosterone (Kaufman and Vermeulen,2005).

35

2015 J)llJr (J4l))!1

2015 JirirJi (;,))J.)l i-.ifrolt:=("tr

Prolactin is 199-amino acid single polypeptide chain with very similar structure to that

of Growth hormone (GH) and human placental lactogen (HLP) (Moustafa et aI.,2O08).lt is

mainly produced by lactotropes ,which normally comprise about l5-25o/o of the anterior

pituitary (adenohypophysis) (Scully and Rosenfled ,2002) and it is also produced by some

immune cells especially lymphocyes.

Testosterone levels in men with diabetes were described to be lower compared to men

withoul a history of diabetes (Stanworth and Jones,2009, Stanworth et al.,2009). There are

epidemiological evidences that low testosterone level is an independent risk factor for the

development of both the metabolic syndrome (Chubb and et a1,2008) and type 2 diabetes

in later lif'e (Stanworth and Jones,2009, Traish el al.,2009). Some studies have debated that

metabolic syndrome may suppress circulating testosterone levels or that low testosterone

induces the metabolic syndrome (Laaksonen et al.,2Ct04; Stellato e/ a1.,2000). Some other

studies have demonstrated that men with type 2 diabetes have lower testosterone levels than

weight-matched non diabetic control subjects (Barrett-Connor ,l 992; Tibblin et a\.,1996).

Dyslipidemia is a term that is commonly used to describe the presence of an increased

serum TG level and /or decreased serum HDL levet (A.DA,2012)

Characteristics of Metabolic Syndrome:

LHypertension (HT): Blood pressure measurement is higher than 140 /90 or the patient wrs

on regular treatment with anti-hypertensive treatment ( Alberti and Zimmet,I 998)

2.Obesity: A patient with BMI >30 was considered as obese ( Alberti and Zimmet,l998)

3. Serum Triglycerides level(TG): TG level >150 mgldl was considered abnormal

(ADA.2003).

4. Serum high density lipoprotein cholestcrol (HDL-C): HDL-C level < 4Omg/dl was

considered abnormal (ADA,2003).

Materiel and Methods

The study was conducted at Department of Physiology, College of Sciences , Wasit

University and the Clinics of diabetes mellitus at Al- Zahra 'l'eaching Hospital and of Al -Karama Teaching Hospital, City of Kut, Iraq during the period from February 2011 to

36

2015 Jr)li.Jl (i!,))r.Jl urlror(r.r(itr

August 201L One hundred and sixty patients attending these clinics and have type 2

diabetes mellitus were enrolled in this study. Their mean age was (49.8 15.7 ) years and the

duration of their disease ranged from ( I -35 ) years .

Medical Examination

Medical history was taken by personal interviewing with the help of a printed

questionnaire. All measurements were undertaken by the same examiner. Exclusion was

made for those who had a concurrent acute illness or another major systematic diseases

except hypertension. Also patients who were taking a lipid lowering agent or were smokers

were excluded. The following clinical characteristics were reported:

I . Age and gender

2. Weight and height in order to calculate body mass index(BMl)

3. Blood pressure lneasurement or a history ofhypertension.

Laboratory analyses:

Specimen:

Subjects were asked to fast for 12 h betbre blood sampling, which was done between

8:00 and 9:00 A.M. Serum was collected for estimation of triglycerides and HDL-C on the

same day of the visit of the patient.

Lipid prolile assay:

Serum total cholesterol and triglyceride level were determined by totally enzymatic

methods (Human company, Germany). Estimation of serum HDL-C was done by

precipitation phosphotungstate-MgCl2 solution followed by enzymetic determination of

cholesterol in the supematant (BioMeriuxe (France). LDL-C was calculated according to

Friedwauld's formula (Friedwauld, etal., I 972)

Hormonal assay

The assay of serum testostertone, and prolactine was done by ELISA kits supplied by

Hnuma company, Cermany while the assay ol serum SHBG was done by ELISA kits

supplied by Kiel company, Germany.

Statistical enalysis:

37

2015 J)li"Jl (rr,)rJl L,Uotsl::trilg

Data were presented in simple statistical measures of number, percentrge, mean and

standard deviation. Statistical analysis was done by using student s t- test for the

significance of difference of quantitative data bet*een two mean vaiues .A probability

value (p<0.05 ) was considered to be statistically significant .

Resultsl,Personal cheractcristics of study groups:

The personal characteristics included the main traditional risk factors for T2DM.The

mean value of body mass index (BMI) for study group was within the range of either

overweight or obese class (29.10 t 4.23) (Table I ).The mean value of HbArc ratio for

study group was higher than normal (9.4 x 2.1 %).

2. Biochemical analytes:

2.1 Lipid prolile

Table (l) also shows the mean values of biochemical analyes of study groups. lt

included the components of lipid profile of the study groups. 'l'he mean level of serum total

cholesterol in study group was (189.1 +37.5 mg /cll), of total triglycerides was ('143.8

+56.3), of high density lipoprotein -+holesterol was 43.0 +10.2 m{dl , and of low density

lipoprotein --cholesterol was (1 t 7.3+31 .8 mg / dl) respectively.

2.2 Hormonal profile

The mean values of hormonal anall.tes of the study patients are shown in table (l). The

mean level of serum testosterone was (4.49 +2.11 ngl ml), of sex hormone binding globulin

was (11.22+9.42 ng/ ml), and of prolactin was(28.88+18.12 ng/ ml) respectively.

3. Hormonal profile oftype 2 diabetic patients according to the resence or absence of

a metabolic characteristic:

Type 2 diabetic disease patients were classified according to the presence or absence of a

certain characteristic of metabolic syndrome in'Iable 4 and as lollows :

Hypertension: No significant difference' in the mean of serum testosterone ,SHBG, and

prolactin were detected between normotensive and hypertensive diabetic patients (Table 2).

Obesity: A significant difference in testosterone level between non obese and

38

2015 J)ti,r\ (;,))!l "-.t!o-r(l{^t*

obese diabetic patients was revealed (P < 0.001) while no significant differences in the

mean level of serum SHBG and prolactin were observed.

TG: No significant differences in the mean levels of serum lestosterone ,SHBG, and

prolactin were detected between normal serum TG and abnormal serum TC groups of

diabetic patient (Table 2).

HDL-C: No significant differences in the mean levels of serum testosterone , SHBG, and

prolactin were detected between groups of normal and abnormal serum HDL-C ('table 2).

4. Factors of dyslipidemia in type 2 diabetic patients according to presence or

absence of a certain metabolic characteristic

(Table 3) shows the analytes ol dyslipidemia in type 2 diabetic patients compared

according to the presence or absence of a certain metabolic characleristic.There was a

significant decrease in HDL-C level in obese compared to non obese diabetic patients.

5. Hormonal profile of type 2 diabetic patients according to accumulation of defined

metabolic characteristics

In table (4 ), sex hormone profile of type 2 diabetic patienls was analyzed according to

accumulation of melabolic characteristics (Diabetic plus hypertension with or without

obesity and dyslipidemia ). In the presence of hypertension and obesity in diabetics, the

SHBG level was sigaificantly increased in comparison with diabetics who were

hypertensive non obese patients (25.16+13.42 vs. 33.58+13.73 respectively , P <0.05 ).

In the presence ofhypertension, obese and lower HDL-C then diabetics had SHBC and

testosterone levels that were significantly decreased in comparison with diabetics who were

hypertensive, obese with higher (or normal) HDL-C level (30.63+14.93 vs.40.7+ 6.33 and

3.73+1.9 vs. 5.57+1.53 respectively , P<0.01) (I'able 4) .

6. Correlations between measures of hormonal profile of study group (type 2diabetic patienfs)

Table 5 showed a highly significant correlation between testosterone and SHBG in

study group ( r:0.407, P < 0.01) while no significant correlation was found between

SHBG and prolactin ('l'able 5).

39

-.rlror(riK^tr

Table l: Personal characteristics and biochemical analytes of study patients

N : number,SD : standsrd deviationTC = Total cholesterol. TG = Triglycerides, HDL-C = High Density Lipoprotein-cholesterol

,LDL-C = low Density Lipoprotein-cholesterol

Characteristic or analyle Range Mean + SD(N= 160)

Age (year) 40-5s 49.E r5.7Duration of DM Qrear) t-24

BMI 29.10 t4.23

Fasting serum sugar( mg/dl)

200.9 +75,2

HbAr"( % ) 4.2 - 15.6 9.4 +2.1

TC( me/dl )

97 .2 - 786

53.8 - 212.1

r89.1+ 37.5

TG( meldl )

t 43.8+ 56.3

HDL-C( mgldl )

43.0+ t 0.2

LDLC( meldl )

83.2 - 209.4 I17.3+ 31.8

Testosteronenglml

l-12,22 4.49+2.11

Sex hormone binding -globulin (nglml)

0.12-141.93 28.EE*18.12

Prolactin (nglml) 1.3-45.55 11.22+9.42

40

2015 Jlli,ll (;,),rJl

3.4 15.2

19.39 - 42,70

8l - 4t9

25.6 - 70.3

2015 JrYli.Jt (;,)r.),Jl -,r},ro!r{ar+

Table 2 : Hormonal profile of type 2 diabetic patients according to the presence orabsence of a metabolic cheracteristic

Metrbolic characteristic(TotEl N= 160 )

Tcstosterone(lvleantSD)

SHBC(MeanrSD)

Prolrctin(MeanlSD)

Hypertension

90(56.3)

4.6*2.22 21.94120.73 t0-55r9.78

Hypertensive 70(43.71

4.53i1.97 J0.08+14.1-l t2.o7*8.92

BMINon Obese 89

(ss.6)4.7 2.17 29.03120.99 10.99r9.J2

Obese 1l(44.4\

J.8E t.87r*P<0.001

28.6Clll.E5 I 1.5+9.58

Normsl 35(2r.e)

d.35+t.7 26.4Jrt3 t 2.611,9.52

Abnormal 125(78.1)

4.5112.21 29.57119_l 10.8-t+9.39

t07(66.9)

.1.3r2.9 21.94+t7.91 10,18*9.37

Aboormal 53(3r.1)

4.88i2.09 30.78*18.58 l2-91!,9.37

HDL.C

N : number, SD: standard deviation,+r: Highly significant

41

Number (Percent %)l

I

TG

NorlrlalI

II

2015 :r-Jl G.,) ,J"Jl i.,UleJ<lLtrilr

of dyslipidemia in type 2 diabetic patients according to presence orTable 3:

absence acertain metabolic characteristic

N : number,SD: standard deviation,**: Highly significant

I

HDL.C(Mean*SD)

mgldlMetrbolic racteristic(Total N= r60 )

Numb€r(Pcrcent 9/o)

TC(Me8n+SD)

mg /dl

Normotensiv€ 90(s6.3)

139.9S+54.88 43.63+10.86ypertensionH

l

Hypertensive 148.7 4+57.99 42.2A*9.6370(43.7)

Non Obese l4l +57.08 45.14*t t.3989(ss.6)

i

BMI

Obese 1t(44.4)

147.31*55.4 40.4t*7.E9**P<0.01

42

2015 J)ti,Jl (;,) ,!l *,uLror(riKirr

12.33+9.19

N : numberSD: standard deviation

SignificantHighly significant

Metabolic characteristic(Total N= 160)

Teslost€ ron e(Mean*SD)

ng/ml

SI{BG(MeantSD)

nglml

Prolactin(Mean+SD)

nglml

DiabeticN: 160

NormotensiveN=90 4.4612.22 27 .94x20.73 10.55+9.78

HypertensiveN=70 4.53+1.97 30.08+14.13 12.07,18.92

DiabrticrHypertensive

N: 70

Non obese

N=294.91+t.94 33.58+13.73 I r.6549.83

ObeseN=41 4,27+1.97 25,16+13.42*

P<0.0512.38*8.32

Normal TGN:8 1.46:L2.18 12.38*8.32

Abnormal TGN=33 4.22x1.96 12.37+6

NormalHDI-CN=29

5.57+t.53 ,t0.7+6.J.3

3.73a1.9r*P<0.01

30.63+14.93**P<0.01

12.4Cr6.08

43

Table 4: Hormonal profire of type 2 diabetic patients according to accumulation ofdefined metabolic characteristics

36.06+I1.59

32.91+14.29Diabetic+

Hypertensive+Obes€N:41

AbnormalHDLCN=12

2015 J)l^,-.Jl (1"1 I'u!t :..,rlro!riKit+

Table 5: Correlations between measures of hormonal profile of study group

( type 2 diabetic pstients)

SHBG

0.00rTestosteron€ 0.407**

SHBC I 0.0t9

**: Highly significant

DiscussionThis stndy has analyzed the association between components of metabolic syndrome

and sex hormone profile ofT2DM diabetic patients in whom MetS is prevalent (Saad and.

Gooren,2009). In analyzing each oomponent separately, our study has shown that obese

diabetics had a significantly lower serum testosterone level than in non obese diabetics.

Such an association has been detected in other studies (Svartberg et a1.,2004; Atlantis e/

a1.,2009:Barett ,1992; Khaw and Barrett, 1992).

In recent years, it has been demonstrated that the fat cell I'unctions as an endocrine cell

that produces and secretes molecules with regulatory potential called cltokines /

adipokines, of which leptin is one prominent representative. ln men, there appears to be a

correlation between body mass index or the fat mass on one hand and leptin levels on the

other. Leptin may be a factor in the association between adiposity and decreased

testosterone levels. Leptin receptors are present on Leydig's cells and inhibit the

testosterone generated by administration of human chorionic gonadotropin (lsidori et

a1.,1999). Visceral obesity with its associated hyperinsulinism suppresses SHBG synthesis

and circulating testosterone plasma levels ( Armin ,2008). Moreover, in obese men, there is

an attenuated pulse amplitude of luteinizing hormone (LH) while the LH pulse frequency is

unaffected, thus producing a weaker stimulation of testicular testosterone production (Lima

et a1.,2000, Vermeulen et al., 1993).

It has also been suggested that the increase in adipose tissue mass in obesity may

result in increased aromatase activity and thus lead to a greater conversion of testosterone

into estradiol (Giagulli et a1.,1994). An increase in estradiol concentrations would lead to

44

Prolsctin

2015 J)Il-Jl (_1.e) r.r,Jt ..^,tlror(riKit+

the suppression of hypothalamic gonadotropin- releasing hormone and pituitary

gonadotropin secretion. This would result in the reduction ofboth testosterone secretion by

Leydig's cells and spermatogenesis in the seminiferous tubules. on statistical analysis,

obesity by itself exerted no significant effect on sHBG but a significant decrease was

shown if hpertension was present as well. Many other reports have showed an association

between SHBG and obesity alone (Jang et al;2011, Samah,2003, Armin , 2008).

ln this study , serum HDL level was significantly lower in obese compared with non

obese diabetics. This is consistent with many other reports (Kolovou et a|.,2005 Ginsberg

and , Huang,2000). Also there was no significant difference in testosterone level between

normal HDL-C and abnormal HDL-C but the difference was apparent and was significant in

the presence of hypertension and obesity. ln this analysis , HDL-C level by itself showed no

significant association with testosterone but a highly significant decrease was shown ifhype(ension and obesity were present as well. This is consistent with other reports that

showed an association between HDL-C and testosterone (Barrett ,1992; Khaw and Banett,

1992 ). Moreover, our study has detected a significant association between IIDL-C and

obesity. Thus, our results go with the definition of metabolic syndrome (Meigs et a|.,2006;

Matik e/ a1.,2005).

In this analysis , HDL-C by itselfexerted no significant effect on SHBG but a significant

decrease was shown if hypertension and obesity were present as well. This is consistent

with other reports that showed an association between HDL-C and sHBC (Goodman el ,/

, 1 996 ; Tchemof et al., I 99 5).

In this analysis ,StlBG was a highly significant correlation with testosterone . This is in

agreement with the finding repo(ed by many studies (Onat el a1"2007; Jang et al'2011)and

is related to the fact that SHBG is the main carrier of testosterone in blood(forkel et

aI.,2009; Paul et a/.,2008).

InConclusion:OurT2DMpatientshaveabadglycemicstateandarecharacterizedby

asignificantlylowerS.Tesmeanleveliftheywereobese'still,theaccumulationofother

core characteristics of MetS which inctudes hypertension and lower S' HDL- C results in a

significantly lower mean levels of both S. Tes and S' SHBG' Obesity' among the other core

45

2015 J)l:i-Jl (1-):.ilt u,utror(ri(a*

independentlyassociatedwithnonalaoholicfa*yliverdiseaseinpeoplewithtype2diabetes

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