Accepted Manuscript Calcium Sensing Receptor in pregnancies complicated by gestational diabetes mellitus Anna Papadopoulou , Evangelia Gole , Athina Moutafi , Costantinos Sfikas , Wolf Oehrl , Martina Samiotaki , Anastasios Papadimitriou , Vasiliki Papaevaggelou , Polyxeni Nicolaidou PII:
S0143-4004(14)00193-3
DOI:
10.1016/j.placenta.2014.05.001
Reference:
YPLAC 2996
To appear in:
Placenta
Received Date: 21 January 2014 Revised Date:
8 May 2014
Accepted Date: 12 May 2014
Please cite this article as: Papadopoulou A, Gole E, Moutafi A, Sfikas C, Oehrl W, Samiotaki M, Papadimitriou A, Papaevaggelou V, Nicolaidou P, Calcium Sensing Receptor in pregnancies complicated by gestational diabetes mellitus, Placenta (2014), doi: 10.1016/j.placenta.2014.05.001. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Calcium Sensing Receptor in pregnancies complicated by gestational diabetes mellitus Abstract Introduction: Infants born from mothers with Gestational diabetes mellitus (GDM)
RI PT
experience several complications, including a higher rate of postnatal hypocalcemia. In this study, we investigated the association between Calcium Sensing Receptor (CaSR) and neonatal hypocalcemia observed in GDM pregnancies.
Methods: Our study consisted of 58 pregnant women with GDM and 40 healthy women and their neonates. CaSR placental expression was evaluated with and
Western
Blot.
Three
CaSR
single
SC
immunohistochemistry
nucleotide
polymorphisms, A986S, R990G, Q1011E, were evaluated in neonate’s genomic
day of life.
M AN U
DNA. Serum Ca, P, Mg, 25(OH)D and PTH were measured in cord blood and at 2nd
Results: GDM neonates had lower mean cord blood Ca levels than controls (2.47±0.21mmol/l vs 2.59±0.13mmol/l, p=0.001) while 15.5% developed postnatal hypocalcemia. CaSR expression was lower in GDM than in healthy placentas (p95th)
RI PT
Mothers
2/58
NS: not significant p-Value. Data are presented as mean ± SD. To describe the differences
EP
between the distribution of categorical variables and the means of the two groups we used 2
AC C
the Chi-Square (χ ) test and the t-test, respectively.
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
ACCEPTED MANUSCRIPT Table 2. Biochemical values in GDM and non-GDM neonates
GDM neonates
Non-GDM neonates
(n=58)
(n=40)
p
Serum of cord blood 2.41±0.23
2.53±0.13
0.004
Albumin (g/l)
37.2±6.4
36.6±2.8
NS
cCa (mmol/l)
2.47±0.21
2.59±0.13
0.001
PTH (ng/l)
8.74(0.1,10)
9.47(3.18,15.89)
0.001
25(OH)D (nmol/l)
32.74±14.58
35.05±16.80
NS
M AN U
SC
RI PT
Ca (mmol/l)
P (mmol/l)
1.82±0.26
1.77±0.19
NS
Mg (mmol/l)
0.76±0.07
0.76±0.10
NS
150.34±56.60
149.95±49.86
NS
3.72±1.16
3.24±0.60
0.017
7.06±1.93
6.66±1.44
NS
0.70±0.13
0.76±0.10
NS
ALP (U/l)
Urea (mmol/l)
Serum of 2nd day of life
2.11±0.22
2.44±0.16
1.87mmol/l
9 (100 %)
28 (61%)
EP
Genotype
TE D
and hypocalcemic levels.
0 (0%)
p-Value 0.023
18 (39%)
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
ACCEPTED MANUSCRIPT • • • •
RI PT
•
We study the Calcium Sensing Receptor in GDM pregnancies GDM neonates have lower fetal and neonatal Ca levels than non GDM neonates CaSR protein is under-expressed in GDM placentas compared with non GDM placentas Reduced CaSR immunostaining in GDM placentas correlates with lower fetal Ca levels Placental CaSR expression levels are dissociated from the neonatal Ca profile
AC C
EP
TE D
M AN U
SC
.
S0143-4004(14)00193-3
DOI:
10.1016/j.placenta.2014.05.001
Reference:
YPLAC 2996
To appear in:
Placenta
Received Date: 21 January 2014 Revised Date:
8 May 2014
Accepted Date: 12 May 2014
Please cite this article as: Papadopoulou A, Gole E, Moutafi A, Sfikas C, Oehrl W, Samiotaki M, Papadimitriou A, Papaevaggelou V, Nicolaidou P, Calcium Sensing Receptor in pregnancies complicated by gestational diabetes mellitus, Placenta (2014), doi: 10.1016/j.placenta.2014.05.001. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Calcium Sensing Receptor in pregnancies complicated by gestational diabetes mellitus Abstract Introduction: Infants born from mothers with Gestational diabetes mellitus (GDM)
RI PT
experience several complications, including a higher rate of postnatal hypocalcemia. In this study, we investigated the association between Calcium Sensing Receptor (CaSR) and neonatal hypocalcemia observed in GDM pregnancies.
Methods: Our study consisted of 58 pregnant women with GDM and 40 healthy women and their neonates. CaSR placental expression was evaluated with and
Western
Blot.
Three
CaSR
single
SC
immunohistochemistry
nucleotide
polymorphisms, A986S, R990G, Q1011E, were evaluated in neonate’s genomic
day of life.
M AN U
DNA. Serum Ca, P, Mg, 25(OH)D and PTH were measured in cord blood and at 2nd
Results: GDM neonates had lower mean cord blood Ca levels than controls (2.47±0.21mmol/l vs 2.59±0.13mmol/l, p=0.001) while 15.5% developed postnatal hypocalcemia. CaSR expression was lower in GDM than in healthy placentas (p95th)
RI PT
Mothers
2/58
NS: not significant p-Value. Data are presented as mean ± SD. To describe the differences
EP
between the distribution of categorical variables and the means of the two groups we used 2
AC C
the Chi-Square (χ ) test and the t-test, respectively.
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
ACCEPTED MANUSCRIPT Table 2. Biochemical values in GDM and non-GDM neonates
GDM neonates
Non-GDM neonates
(n=58)
(n=40)
p
Serum of cord blood 2.41±0.23
2.53±0.13
0.004
Albumin (g/l)
37.2±6.4
36.6±2.8
NS
cCa (mmol/l)
2.47±0.21
2.59±0.13
0.001
PTH (ng/l)
8.74(0.1,10)
9.47(3.18,15.89)
0.001
25(OH)D (nmol/l)
32.74±14.58
35.05±16.80
NS
M AN U
SC
RI PT
Ca (mmol/l)
P (mmol/l)
1.82±0.26
1.77±0.19
NS
Mg (mmol/l)
0.76±0.07
0.76±0.10
NS
150.34±56.60
149.95±49.86
NS
3.72±1.16
3.24±0.60
0.017
7.06±1.93
6.66±1.44
NS
0.70±0.13
0.76±0.10
NS
ALP (U/l)
Urea (mmol/l)
Serum of 2nd day of life
2.11±0.22
2.44±0.16
1.87mmol/l
9 (100 %)
28 (61%)
EP
Genotype
TE D
and hypocalcemic levels.
0 (0%)
p-Value 0.023
18 (39%)
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
ACCEPTED MANUSCRIPT • • • •
RI PT
•
We study the Calcium Sensing Receptor in GDM pregnancies GDM neonates have lower fetal and neonatal Ca levels than non GDM neonates CaSR protein is under-expressed in GDM placentas compared with non GDM placentas Reduced CaSR immunostaining in GDM placentas correlates with lower fetal Ca levels Placental CaSR expression levels are dissociated from the neonatal Ca profile
AC C
EP
TE D
M AN U
SC
.
