Effect of vitamin D supplementation on glucose control in mid-late gestation: A randomized controlled trial

Background & aims It is unclear whether vitamin D supplementation contributes to gestational glucose control and whether the specific effects vary in individuals with diverse genetic and metabolic contexts. The study aimed to assess the effect of vitamin D supplementation during pregnancy on subsequent glucose levels and to identify factors modulating the response to vitamin D3 intake. Methods We conducted a multicenter randomized controlled trial, 1720 pregnant women recruited from the three antenatal clinics of Hefei city, China, who were allocated to receive either 1600 IU/d vitamin D3 (n = 858) or 400 IU/d vitamin D3 (n = 862) for 2 months at 24–28 weeks' gestation. Outcomes were changes in serum 25-hydroxyvitamin D (25(OH)D) and fasting plasma glucose (FPG) levels from baseline, 32–36 weeks’ gestation to delivery (37–41 weeks) quantified using a linear mixed model. Results After 2 months, FPG levels of the control group significantly increased by 0.22 mmol/L (from 4.6 [0.4] mmol/L to 4.8 [1.2] mmol/L, P < 0.001) at delivery, but that of the intervention group had no significant variation (from 4.6 [0.4] mmol/L to 4.7 [1.1] mmol/L; between-group difference in changes, −0.2 mmol/L, 95% CI, −0.3 to −0.08, P = 0.015). And differences in FPG variation were found in participants with the ApaI SNP CC genotype, or BsmI-CC, TaqI-AA, FokI-AA, respectively. Pregnant women with basal 25(OH)D concentrations higher than 50 nmol/L subgroup showed the greatest decline in FPG levels (between-group difference, −0.3 mmol/L; 95% CI, −0.5 to −0.1, P < 0.001). Moreover, pregnant women with GDM, multiple pregnancies or who were overweight were more likely to have FPG decline from vitamin D treatment. Conclusions Vitamin D supplementation significantly protected glucose homeostasis in mid-late gestation, and glycemic response to vitamin D may be dependent on basal 25(OH)D status, VDR gene polymorphism or their metabolic profiles. Trial registration number ChiCTR2100051914. URL of registration http://www.chictr.org.cn/showproj.aspx?proj=134700.