Vitamin D receptor in subcutaneous adipose tissue and serum vitamin D levels relate to gestational diabetes mellitus in overweight/obese pregnant women

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. Key words: Diabetes, gestational; Obesity; Overweight; Adipose tissue; Receptors, calcitriol; Calcitriol