Differences in DNA Methylation in Genes Involved in Vitamin D Metabolism Are Related to Insulin Requirement in Pregnant Women with Gestational Diabetes Mellitus.

In a previous study performed by our group, pregnant women with Gestational Diabetes (GDM) showed higher vitamin D (VitD) levels in the last trimester, particularly in those requiring insulin. This phenomenon was not linked to factors like season or supplementation. This study aimed to investigate if insulin treatment in GDM affects DNA methylation in VitD metabolism genes. Thirty-two pregnant women were selected, half of whom had GDM, and were divided into insulin-treated and lifestyle groups. The DNA methylation levels in CpGs from 47 VitD metabolism-related genes were analyzed at the diagnostic visit (24-28 weeks) and before delivery. At week 36-38 of pregnancy, twenty-six CpG sites were differentially methylated (DMPs) in the insulin-treated group compared with the control group and the lifestyle group. Twenty-two of these DMPs were not different at the diagnostic visit. Six CpGs (cg18276810 (CTNNB1), cg03919554 (FGFR3), cg03984919 (NCOA1), cg19218509 (ASIP), cg09922639 (SMAD3), and cg25356935 (PDZD3)) showed significant correlations with VitD levels, not only before childbirth, but also in the postpartum period and at one year later. This suggests that insulin treatment in GDM could influence DNA methylation in genes involved in vitamin D metabolism, affecting VitD levels during and after pregnancy. Further research is warranted to elucidate these findings' clinical implications.

Insulin Requirement for Gestational Diabetes Control Is Related to Higher Vitamin D Levels up to 1 Year Postpartum: A Prospective Cohort Study.

Vitamin D deficiency is highly prevalent in pregnant women and has been related to a higher risk of gestational diabetes mellitus (GDM). The aim of this study is to analyze vitamin D status evolution in a population of pregnant women with and without GDM. Two-hundred women were included from January 2019 to February 2022 as follows: Control group -CG-, Lifestyle group -LG- (GDM not requiring insulin), and Insulin group -IG- (GDM requiring insulin). Visits were carried out at baseline, antenatal, postpartum, and 1 year after birth. Vitamin D levels, weight, and insulin resistance were measured at every visit. Data about the season, vitamin D supplementation, Mediterranean diet adherence, and physical activity were included. In the three groups, 134 women were included in the CG, 43 in the LG, and 23 in the IG. Vitamin D levels were similar among the groups at baseline, but they were significantly higher in the LG and IG in comparison with the CG at the antenatal visit and significantly higher in the IG vs. CG and LG at the postpartum and 1 year after birth visits. Vitamin D levels were independently related to vitamin D supplementation and the season at baseline, to the season and belonging to the LG or IG at the antenatal visit, and were only independently associated with belonging to the IG at postpartum and 1 year after birth visits. In conclusion, in our population, women with GDM requiring insulin had higher levels of vitamin D in comparison with those not requiring insulin and healthy controls at postpartum and 1 year after pregnancy. Requiring insulin during pregnancy seems to be a factor that independently determines the levels of vitamin D until 1 year after birth. More studies are required to reproduce these data in other populations and to elucidate the mechanisms underlying these findings.