Expression And Significance Of Vitamiin D And Related Genes In Placental Tissue Of Gestational Diabetes Mellitus

Gestational diabetes mellitus(GDM)is characterized by normal glucose metabolism before pregnancy and impaired glucose tolerance after pregnancy.To date,the pathogenesis of GDM is still unclear,insulin resistance and impaired islet cells are the main pathogenesis,in addition,some studies have found that vitamin D can also improve insulin resistance and promote the secretion of insulin,vitamin D deficiency significantly increases the risk of GDM,but the specific mechanism remains to be further discussed.Objectives: The aim was to investigate the pathogenesis of vitamin D and related genes in GDM by measuring the levels of vitamin D and vitamin D receptor(VDR)in maternal blood and umbilical cord blood of the GDM group and the normal pregnancy group(NGT),as well as the relative expression levels of vitamin D-related genes in placental tissues.Methods: According to the OGTT results of 24-28 weeks of pregnancy,81 pregnant women in the third trimester who underwent elective cesarean section in our Hospital were divided into GDM group(41 cases)and normal pregnancy group(40 cases).Fasting venous blood of the pregnant was extracted before the operation,umbilical cord blood and placental tissues were collected after the delivery of the fetus.Plasma vitamin D and VDR levels were measured by electrochemical luminescence and ELISA,the relative expressions of CYP24A1,CYP27B1,VDR m RNA and proteins in placental tissues were measured by RT-PCR and Western Blot.Results: 1.Serum Vitamin D concentrations were significantly lower in women with GDM than normal pregnant both in maternal blood(14.19±4.46 vs.19.16±7.97,P<0.01)and cord blood(15.93±6.57 vs.19.60±6.61,P=0.014).In addition,the proportion of patients with maternal blood vitamin D deficiency in the people with gestational diabetes was obviously higher than that in the normal pregnant(87.80% vs.65%,P=0.015,OR=3.877).The concentration of maternal blood VDR in the GDM group(26.23±4.82 vs.23.13±7.40,P=0.028)was distinctly higher than that in the normal pregnancy group.However,the difference of umbilical blood VDR between the GDM and NGT groups was not statistically significant.Maternal blood vitamin D showed positive correlation with insulin sensitivity index,and negative correlation with fasting insulin and Homeostasis model assessment-insulin resistance index.2.The expression level of CYP24A1 m RNA(2.71±1.77 vs.1.61±0.66,P=0.021)and VDR m RNA(2.32±1.37 vs.1.10±0.50,P=0.023)in the people with GDM were obviously higher than those in the normal pregnant,while CYP27B1 m RNA(1.03±0.64 vs.1.68±0.69,P=0.042)in GDM groups was obviously lower than that in NGT groups.3.The expression level of CYP24A1 protein(1.69±0.16 vs.1.12±0.17,P<0.01)and VDR protein(0.94±0.26 vs.0.79±0.16,P=0.026)in the people with GDM were distinctly higher than those in the normal pregnant,while CYP27B1 protein(1.06 ± 0.16 vs.1.56 ± 0.19,P<0.01)was distinctly lower than that in the normal pregnant.4.In the GDM group,maternal plasma vitamin D level showed a positive relationship with umbilical cord plasma vitamin D level(r=0.707,P<0.01)and placenta CYP27B1 protein(r= 0.598,P<0.01).Conversely,it had negative relationship with maternal plasma VDR(r=-0.352,P<0.01),placenta CYP24A1 protein(r=-0.593,P<0.01),placenta CYP24A1 m RNA(r=-0.657,P<0.01)and placenta VDR protein(r=-0.536,P<0.01).Conclusions: 1.Vitamin D deficiency may be involved in the development of GDM by increasing insulin resistance and reducing insulinsecretion secretion.Among them,25(OH)D<20ng/ml is a risk factor of GDM,and the lower the vitamin D level,the higher the risk of GDM.2.Maternal vitamin D levels may influence fetal vitamin D levels through the placental barrier.3.Changes in vitamin D metabolism-related genes may be involved in gestational diabetes by affecting the concentration and activity of vitamin D.