Original Article

SERUM PROLACTIN LEVELS IN TYPE-II DIABETES MELLITUS WITH RETINOPATHY

PATIENTS IN AND AROUND HYDERABAD
Mohammed Abdullah Saad1, Mohammed Sabiullah2, N. Vani N3.
1
Resident specialist, Department of Biochemistry, Niloufer Hospital, Hyderabad, Telangana.
2
Associate professor, Department of Biochemistry, Osmania Medical College, Ko , Hyderabad, Telangana.
3
Professor and Head, Department of Biochemistry, Osmania Medical College, Ko , Hyderabad, Telangana.

ABSTRACT
Background & Objec ves: Diabetes is a disease of metabolic dysregula on. Hyperglycemia and oxida ve stress
play a role in the development of late diabe c complica ons. Increased re nal vasopermeability occurs early in dia-
betes and is crucial for the development of sight-threatening diabe c re nopathy. Serum prolac n is proteoly cally
processed to vasoinhibins that inhibit the excessive re nal vasopermeability related to diabe c re nopathy. The aim
is to study the role of serum prolac n in the pathogenesis of re nopathy in type 2 diabe cs and to correlate the
changes in serum prolac n levels. Methods: A case control study was done with 90 pa ents divided into 3 groups
(healthy controls, Type 2 Diabetes without re nopathy and Type 2 Diabetes with re nopathy) with inclusion and
exclusion criteria. Fas ng blood samples were collected and fas ng plasma glucose, serum Prolac n were measured.
Mul ple comparisons between different groups were done using ANOVA test. Results: In the present study de-
creased serum prolac n levels were observed in pa ents of Type 2 Diabetes with re nopathy compared to Type 2
Diabetes without re nopathy and controls. Mean ± S.D of Fas ng plasma glucose, was highest in Group 3. Mean ±
S.D of serum prolac n (7.737 ± 2.63) was low in Group 3. Conclusion: The circula ng levels of prolac n were de-
creased in pa ents with diabe c re nopathy due to glycosyla on and were higher in diabe c pa ents without re -
nopathy and healthy controls. Increased prolac n levels influence the progression of re nopathy a er its intraocular
conversion to vasoinhibins which can reduce the pathological re nal vasopermeability in diabetes and increase in
prolac n can be considered to have protec ve role in pathogenesis of diabe c re nopathy and also may be consid-
ered as a treatment op on for re nopathy.
Key words: Diabe c re nopathy, Prolac n, Re nal vasopermeability, Vasoinhibins.

formed blood vessels (neovasculariza on) extend and

INTRODUCTION
Diabetes Mellitus is a chronic disease which has serious
metabolic disturbances in carbohydrate, protein and
fat metabolism occurring due to insulin insufficiency or
its ac on. Excessive release of free radicals due to in-
crease in oxida ve stress in diabetes, leads to diabe c
complica ons such as re nopathy [1].
In diabe c re nopathy, loss of pericytes and endotheli-
al cells causing abnormally permeable re nal capillar-
ies. In early stages, increased re nal vasopermeability
leads to intrare nal hemorrhages and exudates that,
along with capillary closure, produces nonperfusion
areas. Eventually, the resul ng hypoxia s mulates the
produc on of proangiogenic factors locally, such as
vascular endothelial growth factor (VEGF); the newly
DOI: 10.5455/ijcbr.2017.34.09
bleeds into the vitreous gradually, causing detachment
of the re na from the accompanying fibrous ssue
leading to loss of vision in the pa ents [2].
A polypep de hormone prolac n, synthesized in the
anterior pituitary cells. Cathepsin-D or matrix metallo-
proteases cleaves serum prolac n to produces pep de
fragments known as Vasoinhibins [3,4] which reduces
vasodila on and also prevents angiogenesis and re nal
vasopermeability associated with diabetes [5].
Current treatments for diabe c re nopathy such as
laser photo-coagula on and vitrectomy, are usually
effec ve but may be damaging as well, and can only
treat the later stages of the disease. Hence, working on
new strategies to prevent both increased re nal vasop-
ermeability and angiogenic responses has become a
major research focus.
MATERIAL AND METHODS

Study design: Case control analy cal study

eISSN: 2395-0471
pISSN: 2521-0394 Ethics approval: The study was approved by the ins -
tu onal ethics commi ee and informed consent was
taken from the all par cipants.

Correspondence: Mohammed Sabiullah, Associate professor, Department of Biochemistry,

Osmania Medical College, Koti, Hyderabad, Telangana. Email: mohammadsabiullah@gmail.com
International Journal of Clinical and Biomedical Research. © 2017 Sumathi Publications.
This is an Open Access article which permits unrestricted non-commercial use, provided the original work is properly cited. 39
Mohammed Sabiullah et al.  Serum Prolactin Levels in Type-II Diabetes Mellitus With Retinopathy Patients

Study loca on: Inves ga ons were performed at the sults are expressed as Mean±SD of various parameters
Department of Biochemistry, Osmania in different groups, to assess the significance of the
differences observed in the mean values of different
Medical College/ Osmania General Hospital, Hydera- parameters observed in different groups studied, the
bad. data is subjected to ANOVA test. The significance of
Study dura on: December 2014 to May 2016. difference of mean values of different groups and with-
in the groups is represented by p value <0.05 is consid-
Sample size: case control study was done with 90 pa- ered as significant. Pearson’s correla on was done to
ents assess the correla on of parameters within each group.
Inclusion criteria: Table 1. Study parameters in all groups
Cases: Case samples were collected from diabe c pa- Group 1 Group 2 Group 3
Parame-
ents of age group 35-65 years, Department of Re na,
ter Mean ±S.D Mean ±S.D Mean ±S.D
Sarojini Devi Eye Hospital, Mehdipatnam, Hyderabad.
F.P.G 84.20± 127.7± 163.7±
Control: 30 healthy male voluntary blood donors of
(md/dl) 9.152 35.90 76.88
same age were taken as controls.
S. PRL 7.737±
12.84±5.77 17.98±5.631
Exclusion criteria: Females, due to significant varia ons (ng/ml) 2.63
in hormone levels at different ages, medical history of
prolac noma, hypothyroidism, chronic renal failure, Table 2. Pearsons Correla on between parameters in
liver cirrhosis, Treatment with Drugs that increase pro- control group
lac n levels, Recent psychologic stress, recent hospital-
FPG S.PRL
iza on, acromegaly and cushing disease.
Pearsons correla-
0.166
Grouping: FPG on
Sig. (2tailed)N 0.382
Group 1 included healthy controls who were matched
Pearsons correla-
for age. 0.166
S.PRL on
Group 2: Diabe c pa ents those individuals who were Sig. (2tailed)N 0.382
recently diagnosed as diabe c. They were under gly-
caemic control by receiving either Insulin or oral hypo-
Table 3. Pearsons Correla on between parameters in
glycaemic drugs and didn’t have any complica ons.
group 2
This group of pa ents had a normal fundus examina-
on. FPG S.PRL
Group 3: Chronic cases of Diabe c, also under treat- Pearsons correla on 0.006
ment with an diabe c drugs. They had developed re - FPG
Sig. (2tailed)N 0.975
nopathy and were selected based on fundus examina-
on by an ophthalmoscope. The minimum requirement Pearsons correla on 0.006
S.PRL
for a diagnosis of re nopathy was the presence of Sig. (2tailed)N 0.975
background re nopathy classified as microaneurysms,
haemorrhages, exudates or venous beading. [6] Table 4. Pearsons Correla on between parameters in
group 3
Methodology:

Pa ent details including age, sex, medical history, on- FPG S.PRL
set, dura on and complica ons of Diabetes were filled Pearsons correla-
in a proforma. Fas ng blood samples were collected -0.378
FPG on
from all the study par cipants of each group under Sig. (2tailed)N 0.039
asep c condi ons in serum vacutainers (Red cap) and
Pearsons correla-
es mated fas ng plasma glucoses levels by Trinder’s -0.378
S.PRL on
method (Glucose oxidase- Peroxidase).[7] The remain-
ing serum was stored at –200C in an aliquot for serum Sig. (2tailed)N 0.039
prolac n es ma on. Grossly hemolysed and lipemic
RESULTS
were excluded. Serum prolac n was measured by ELISA
method. [8] The Mean ± SD of all the parameters studied in the
total cases were significantly different from those of
Sta s cal analysis: Data analysis was done using
controls (p<0.05). Mean value of Serum prolac n was
GraphPad Prism so ware version 7.0. Descrip ve re-
lowest in Group 3 followed by Group 1 and Group 2.

Int. j. clin. biomed. res. 2017;3(4):39-43 40

Mohammed Sabiullah et al.  Serum Prolactin Levels in Type-II Diabetes Mellitus With Retinopathy Patients
Mean value of fas ng plasma glucose, was highest in
Group 3 followed by Group 2 and Group 1. In Group 1&
2, Serum prolac n was posi vely correlated with
fas ng plasma glucose, but was not sta s cally signifi-
cant. In Group 3, Serum prolac n was nega vely corre-
lated with fas ng plasma glucose but it was sta s cally
significant. Results showed that type 2 Diabetes pa-
ents with re nopathy had lower levels of serum pro-
lac n when compared to type 2 Diabetes pa ents with-
out re nopathy and healthy controls.
DISCUSSION
Diabe c re nopathy may be the most common micro-
vascular complica on of diabetes. The proposed patho-
physiological mechanisms by which diabetes may leads
to development of re nopathy are as follows:[24]
 Hyperglycemia increases the flux of sugar molecules
through the polyol pathway, causing sorbitol accu-
mula on in cells, eventually producing osmo c
stress considered to be an underlying mechanism in
the development of diabe c microvascular compli-
ca ons, including diabe c re nopathy.
 Hyperglycemia can promote the nonenzyma c for-
ma on of advanced glycosylated end products
(AGEs) which are thought to damage the cell.
 High glucose levels can s mulate free radical pro-
duc on and reac ve oxygen species forma on
causing cell injury.
 Growth factors, including vascular endothelial
growth factor (VEGF), growth hormone, and trans-
forming growth factor β, have also been postulated
to play important roles in the development of dia-
be c re nopathy.
Vasoinhibins are a family of prolac n (PRL) fragments
with an angiogenic property[9] that inhibit ischemia-
induced re nal angiogenesis[10] and prevent increased
re nal vasopermeability associated with diabetes.[11]
This proteoly c product of prolac n acts as a potent
inhibitor of angiogenesis in vivo and in vitro, inhibi ng
the prolifera on of endothelial cells.[12,13] Vasoin-
hibins are considered as endogenous regulators of an-
giogenesis and vascular func on.[14] In vitro experi-
ments and in vivo studies revealed that vasoinhibins
inhibit neovasculariza on by[15] apoptosis-mediated
vascular regression, thus being a potent inhibitor of
angiogenesis in the re na[16] and elsewhere. In addi-
on, vasoinhibin can inhibit endothelial cell prolifera-
on and vasopermeability in the re nal vessels of dia-
be c pa ents, induced by vascular endothelial growth
factor (VEGF)[12]. Serum prolac n levels were signifi-
cantly lower in group 3 when compared to group 1&2,
implying type 2 Diabetes pa ents with microvascular
complica ons like re nopathy had highest levels of
glucose than type 2 Diabetes pa ents without micro-
vascular complica ons and controls. It can be explained
Int. j. clin. biomed. res. 2017;3(4):39-43
as diabe c pa ents with complica ons had poor gly-
caemic control, leading to the increased glyca on of
proteins, forming advanced glycated end products. The
protec ve effect of vasoinhibin (PRL-V) against neovas-
culariza on (angiogenesis) may be reduced in diabe c
pa ents because of the lower levels of PRL due to in-
creased glycosyla on of PRL (G- PRL) which exhibits
decreased receptor binding and increased metabolic
clearance. [17,18] This puts the diabe cs at an in-
creased risk for the developing of re nopathy in future.
Study conducted by Arnold E. et al. [19] showed signifi-
cant decreased in serum prolac n levels in the Type 2
diabe c pa ents with diabe c re nopathy in later stag-
es, and observed significant difference in serum prolac-
n levels between healthy control and Type 2 diabe c
pa ents with prolifera ve diabe c re nopathy. And
also, the difference of serum prolac n levels between
individuals with Type 2 Diabe cs without re nopathy
and Type 2 Diabetes with later stages of diabe c re -
nopathy was significant. Mar ni et al. [20] have
demonstrated that fragment of human prolac n (hPRL)
induces apoptosis of endothelial cells. Low levels of
serum prolac n may not prevent the development of
new blood vessel in the re na of diabe c pa ents.
Struman et al. [21] have shown that recombinant N-
terminal fragments of human prolac n have an angio-
genic proper es, which can prevent the neovascularisa-
on in the re na of diabe c pa ents. Carmen Gonzalez
et al. [22] Showed that prolac n fragments inhibit vas-
cular endothelial growth factor (VEGF)- induced eNOS
(Nitric oxide synthase) ac va on and endothelial cell
prolifera on [12] and concluded that those fragments
can block the ac va on of eNOS which results in inhibi-
on of angiogenesis both in vivo and in vitro. In com-
parison with the present study, Mooradian A. et al. [23]
measured fas ng serum prolac n levels in 72 diabe c
males and compared the results with those of 63
healthy males. The diabe c group had significantly
higher serum prolac n levels than the control group.
18% percent of the diabe cs studied had serum prolac-
n levels above the normal range for males (> 20 ng/
mI). But there was no correla on between serum pro-
lac n levels and presence of clinically apparent re -
nopathy in this study. Celina García et al. [11] observed
prolac n to be an important systemic inhibitor of dia-
betes-induced re nal hypervasopermeability a er its
intraocular conversion to vasoinhibins, which act di-
rectly on endothelial cells to block blood vessel growth,
dila on, and permeability and to promote apoptosis-
mediated vascular regression. Promo ng vasoinhibin
ac vity to counteract vascular endothelial growth fac-
tor and reduce excessive re nal vasopermeability in
diabe c re nopathy emerges from this study as a po-
ten ally powerful therapeu c approach for effec ve
treatment of diabe c macular edema and other vas-
oprolifera ve re nopathies.
41
Mohammed Sabiullah et al.  Serum Prolactin Levels in Type-II Diabetes Mellitus With Retinopathy Patients
CONCLUSION
In this study, we observed decreased serum prolac n
levels in pa ent with diabe c re nopathy when com-
pared to diabe c pa ents without re nopathy and
healthy controls. Thus we concluded that serum prolac-
n proves to be important in the pathogenesis and
progression of diabe c re nopathy and promo ng vas-
oinhibin (fragment of prolac n) ac vity may reduce
excessive re nal vasopermeability and neovasularisa-
on in diabe c re nopathy and is emerging as a poten-
ally powerful therapeu c approach for effec ve treat-
ment of prolifera ve diabe c re nopathy and other
vasoprolifera ve re nopathies.
Acknowledgment: We acknowledge the services pro-
vided by MDR unit Osmania medical college, Hydera-
bad to carry out this research.
Conflict of interest: Nil
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How to Cite this article: Mohammed Abdullah Saad1, Mohammed Sabiullah, N. Vani N. Ser um Ser um Pr olactin Levels in
Type-II Diabetes Mellitus With Retinopathy Patients in and Around Hyderabad. Int j. clin. biomed. Res. 2017;3(4) : 39-43

Int. j. clin. biomed. res. 2017;3(4):39-43 43