Features of vitamin D metabolism and regulation ofcalcium-phosphate homeostasis during pregnancy

Background. Gestational diabetes mellitus is a common metabolic complication of pregnancy characterized by impaired glucose tolerance first detected during gestation. Gestational diabetes mellitus affects a substantial proportion of pregnant women worldwide and is associated with an increased risk of adverse maternal and neonatal outcomes. Vitamin D, a secosteroid hormone traditionally known for its role in calcium and phosphorus homeostasis and skeletal health, has attracted growing attention due to its potential involvement in glucose metabolism and insulin regulation. Despite accumulating evidence linking vitamin D status with gestational diabetes mellitus, study results remain inconsistent, particularly regarding the clinical relevance of vitamin D metabolites beyond total 25(OH)D and the dynamic changes in vitamin D metabolism throughout pregnancy. This highlights the need for comprehensive metabolic profiling to better understand how alterations in the vitamin D metabolome during pregnancy are related to calcium-phosphorus balance and the development of gestational diabetes mellitus. Objective. To investigate the features of vitamin D metabolism and calcium-phosphorus homeostasis in pregnant women and their association with gestational diabetes mellitus. Materials and methods. A single-center, observational, prospective, comparative study was conducted. Women with gestational diabetes mellitus (n = 35) underwent longitudinal assessment in the second and third trimesters, including evaluation of multiple components of the vitamin D metabolome using high-performance liquid chromatography coupled with tandem mass spectrometry. For comparison, a control group of conditionally healthy pregnant women (n = 37), matched for age, was formed (p = 0.501). Results. In the second and third trimesters of pregnancy, women with gestational diabetes mellitus showed biochemical parameters of calcium-phosphorus metabolism that remained within the reference range and did not differ significantly from the control group. Concentrations of 25(OH)D3 and other vitamin D metabolites in women with gestational diabetes mellitus were largely comparable to controls, with a statistically significant reduction observed only for 24,25(OH)2D3 in the second trimester. No differences were found in the ratios of vitamin D metabolites reflecting the activity of key metabolic enzymes. During pregnancy, women with gestational diabetes mellitus demonstrated a decrease in albumin levels with stable albumin-corrected calcium, as well as a trend toward increased concentrations of 3-epi-25(OH)D3 and 24,25(OH)2D3 by the third trimester. Conclusion. Pregnant women with gestational diabetes mellitus exhibit lower serum 25(OH)D3 concentrations in the second trimester and reduced levels of the metabolites 1,25(OH)2D3 and 24,25(OH)2D3 in the third trimester compared with the control group. Ratios between vitamin D metabolites reflecting the activity of key enzymes involved in vitamin D metabolism remain stable, indicating preserved enzymatic regulation. The observed differences are most likely attributable to baseline vitamin D status rather than to disturbances in enzymatic metabolism. Thus, the results of the present study, together with an analysis of current clinical guidelines, support the rationale for continuous vitamin D supplementation from the first trimester of pregnancy until delivery. These findings highlight the importance of early (preconception) assessment of 25(OH)D3 status and timely correction of its levels to optimize the metabolic profile and reduce the risk of gestational diabetes mellitus during pregnancy.