ABSTRACT
Objective To investigate the differences in the expression of vitamin D receptor (VDR) and serum vitamin D levels in subcutaneous adipose tissue between overweight/obese and normal-weight gravidas, and the relationship between these two indicators and gestational diabetes mellitus (GDM). Methods Women with full-term singleton pregnancies who underwent elective cesarean section in Changzhou Maternal and Child Health Care Hospital Affiliated to Nanjing Medical University from January 2015 to April 2017 were enrolled. Among them, there were 70 cases GDM women, including 35 normal-weight (NW-GDM group) and 35 overweight/obese women (OW-GDM group). During the same period, another 70 pregnant women with normal glucose tolerance who underwent scheduled cesarean delivery were selected as the control group, including 35 normal weight women (NW-control group) and 35 obese/overweight women (OW-control group). Fasting blood samples were collected before operation to determine the levels of different biomarkers, including vitamin D, lipid, fasting blood glucose, fasting insulin and adiponectin, and to calculate the homeostasis model assessment-insulin resistance (HOMA-IR). Two subcutaneous adipose tissue samples of the abdominal wall were taken during the operation to detect the expression and distribution of VDR protein with immunohistochemistry. Meanwhile, VDR mRNA transcription level was quantitatively analyzed using real-time fluorescence quantitative polymerase chain reaction. One-way analysis of variance, LSD, Kruskal-Wallis test, Mann-Whitney U test, Chi-square test and logistic regression analysis were used for statistical analysis. ResuLts (1) The body mass index (BMI) of the OW-control group and the OW-GDM group before pregnancy and delivery were all higher than that of the NW-control group and the NW-GDM group [BMI before pregnancy: (29.2±2.9), (29.4±3.8) vs (21.1±2.3) and (21.9±2.0) kg/m2, F=87.766; BMI before delivery: (35.2±3.4), (35.1±4.3) vs (27.9±2.8) and (28.8± 3.3) kg/m2, F=44.827; all P<0.001]. Newborn birth weight and the proportion of diabetic family history in the OW-GDM group were higher comparing to the NW- and OW- control group [(3 893±498) vs (3 501±402) and (3 625±332) g, F=4.751; 22.9%(8/35) vs 5.7%(2/35) and 5.7%(2/35), χ2=7.869; all P<0.05]. (2) In the OW-control group, the fasting insulin level and HOMA-IR were higher and the adiponectin and vitamin D concentration were lower than those in the NW-control group [13.3(12.3-14.5) vs 12.0(10.4-13.3) mmol/L, 2.7(2.4-3.0) vs 2.2(2.0-2.7), (61.8±20.4) vs (74.9±29.3) ng/ml, (21.6±7.2) vs (25.9±7.3) ng/ml; all P<0.05], and similar results were found between the OW-GDM group and the NW-GDM group [15.3(12.3-19.5) vs 12.0(10.1-15.8) mmol/L, 3.4(2.6-4.1) vs 2.6(2.1-3.2), (50.3±22.3) vs (62.1±23.2) ng/ml, (17.1±6.7) vs (20.6±7.9) ng/ml, all P<0.05]. Compared with the NW-control group, the NW-GDM group had higher fasting glucose and lower high density lipoprotein-cholesterol (HDL-C), adiponectin and vitamin D levels [4.6(4.3-5.1) vs 4.3(4.0-4.5) mmol/L, 1.7(1.6-1.9) vs 2.1(1.6~2.4) mmol/L, (62.1±23.2) vs (74.9±29.3) ng/ml, (20.6±7.9) vs (25.9±7.3) ng/ml; all P<0.05]. Compared with the OW-control group, fasting glucose, fasting insulin and HOMA-IR were higher and HDL-C, adiponectin and vitamin D levels were lower in the OW-GDM group [4.7(4.4-5.4) vs 4.5(4.2-4.7) mmol/L, 15.3(12.3-19.5) vs 13.3(12.3-14.5) mmol/L, 3.4(2.6-4.1) vs 2.7(2.4-3.0), 1.6(1.4-1.8) vs 1.9(1.7-2.2) mmol/L, (50.3±22.3) vs (61.8±20.4) ng/ml, (17.1±6.7) vs (21.6±7.2) ng/ml; all P<0.05]. (3)The overall vitamin D deficiency rate during the third trimester of the four groups was 78.6% (110/140), and the figure was 62.8% (22/35), 82.8% (29/35), 77.1% (27/35) and 91.4% (32/35) in the NW-control group, OW-control group, NW-GDM group and OW-GDM group (χ2=8.994, P=0.029), indicating a higher rate in the OW-GDM group than that in the NW-control group (χ2=8.102, P=0.004). (4) VDR was expressed in the nucleus of adipose tissue in all samples and statistic difference in protein expression was found among the four groups. VDR mRNA expression was higher in both GDM subgroups than that in the two control subgroups, and also higher in the two overweight/obese subgroups than in the corresponding normal-weight subgroups. (5)Serum vitamin D level was negatively correlated with fasting blood glucose and pre-pregnancy BMI, and positively correlated with adiponectin (P<0.05). The incidence of GDM was related to family history of diabetes, VDR mRNA, total cholesterol, HDL-C and HOMA-IR. ConcLusions GDM and overweight/obese patients had decreased serum vitamin D level and increased VDR in subcutaneous adipose tissue. These two factors are closely related to GDM.
ABSTRACT
Objective To investigate the incidence of subclinical hypothyroidism (SCH) during the third trimester of pregnancy and its effects on pregnancy outcomes and neonatal hypothyroidism.Methods A total of 10 695 women in the third trimester of pregnancy (28-42 weeks of gestation) who labored from January 1,to December 31,2012 in Changzhou Maternal and Child Health Care Hospital Affiliated to Nanjing Medical University were enrolled.The levels of thyroid stimulating hormone (TSH),free thyroxine (FT4) and thyroid peroxidase antibody (TPOAb) of the mothers were quantified by electrochemical immunoassay.The time-resolved fluorescence immunoassay was used to detect neonatal thyroid hormone levels.Using t test or x2test,the incidence of adverse pregnancy outcomes was compared between SCH group and euthyroid group and between SCH women with positive (n=40) or negative TPOAb (n=176).Results The incidence of SCH was 2.02％ (216/10 695) and the positive rate of TPOAb in SCH women was 18.5％ (40/216).No neonatal thyroid dysfunction was found.According to the age matched,222 cases were randomly selected as controls from 7 757 euthyroid women.Compared with the controls,SCH women had a higher incidence of premature rupture of membranes [28.7％ (62/216) vs 14.9％ (33/222),x2=12.34],anemia [11.6％ (25/216) vs 4.1％ (9/222),x2=8.65],pregnancy-induced hypertension [9.7％ (21/216) vs 4.5％ (10/222),x2=4.53],premature labor [8.8％ (19/216) vs 3.6％ (8/222),x2=5.10] and intrahepatic cholestasis of pregnancy [8.3％(18/216) vs 2.3％ (5/222),x2=8.14] (all P＜0.05).The overall incidence of adverse pregnancy outcomes was also higher in SCH group than in the controls [69.4％ (150/216) vs 49.5％ (110/222),x2=17.96,P＜0.01].The incidence of fetal growth restriction and still birth in SCH mothers with positive TPOAb was higher than in those with negative TPOAb [7.5％ (3/40) vs 0.0％ (0/176),x2=13.32,P＜0.01; 2.5％ (1/40) vs 0.0％ (0/176),x2=4.40,P＜0.05],but there was no significant difference in the overall incidence of adverse pregnancy outcomes compared with TPOAb-negative mothers [65.0％ (26/40) vs 70.5％ (124/176),x2=0.46,P=0.50].Conclusions SCH diagnosed in the third trimester may lead to adverse pregnancy outcomes.Early screening for thyroid dysfunction is necessary.