In this prospective controlled study, we examined 25 adults with adequately controlled (HbA1c level < 8.0%) type 1 diabetes mellitus (T1DM) and 49 conditionally healthy adults, intending to reveal the diversity of vitamin D metabolism in the setting of cholecalciferol intake at a therapeutic dose. All patients received a single dose (150,000 IU) of cholecalciferol aqueous solution orally. Laboratory assessments including serum vitamin D metabolites (25(OH)D₃, 25(OH)D₂, 1,25(OH)₂D₃, 3-epi-25(OH)D₃ and 24,25(OH)₂D₃), free 25(OH)D, vitamin D-binding protein (DBP) and parathyroid hormone (PTH) as well as serum and urine biochemical parameters were performed before the intake and on Days 1, 3 and 7 after the administration. The studied groups had no significant differences in baseline parameters except that the patients with diabetes showed higher baseline levels of free 25(OH)D (p < 0.05). They also lacked a correlation between the measured and calculated free 25(OH)D in contrast to the patients from the control group (r = 0.41, p > 0.05 vs. r = 0.88, p < 0.05), possibly due to the glycosylation of binding proteins, which affects the affinity constant for 25(OH)D. The elevation of vitamin D levels after the administration of cholecalciferol was comparable in both groups, with slightly higher 25(OH)D₃ levels observed in the diabetes group throughout the study since Day 1 (p < 0.05). Overall, our data indicate that in patients with adequately controlled T1DM 25(OH)D₃ levels and the therapeutic response to cholecalciferol is similar to that in healthy individuals.

In this study we aimed to assess vitamin D metabolism in patients with Cushing’s disease (CD) compared to healthy individuals in the setting of bolus cholecalciferol treatment. The study group included 30 adults with active CD and the control group included 30 apparently healthy adults with similar age, sex and BMI. All participants received a single dose (150,000 IU) of cholecalciferol aqueous solution orally. Laboratory assessments including serum vitamin D metabolites (25(OH)D₃, 25(OH)D₂, 1,25(OH)₂D₃, 3-epi-25(OH)D₃ and 24,25(OH)₂D₃), free 25(OH)D, vitamin D-binding protein (DBP) and parathyroid hormone (PTH) as well as serum and urine biochemical parameters were performed before the intake and on Days 1, 3 and 7 after the administration. All data were analyzed with non-parametric statistics. Patients with CD had similar to healthy controls 25(OH)D₃ levels (p > 0.05) and higher 25(OH)D₃/24,25(OH)₂D₃ ratios (p < 0.05) throughout the study. They also had lower baseline free 25(OH)D levels (p < 0.05) despite similar DBP levels (p > 0.05) and lower albumin levels (p < 0.05); 24-h urinary free cortisol showed significant correlation with baseline 25(OH)D₃/24,25(OH)₂D₃ ratio (r = 0.36, p < 0.05). The increase in 25(OH)D₃ after cholecalciferol intake was similar in obese and non-obese states and lacked correlation with BMI (p > 0.05) among patients with CD, as opposed to the control group. Overall, patients with CD have a consistently higher 25(OH)D₃/24,25(OH)₂D₃ ratio, which is indicative of a decrease in 24-hydroxylase activity. This altered activity of the principal vitamin D catabolism might influence the effectiveness of cholecalciferol treatment. The observed difference in baseline free 25(OH)D levels is not entirely clear and requires further study.

BACKGROUND: Vitamin D (25-hydroxyvitamin D [25(ОН)D]) deficiency (<20 ng/mL) and insufficiency (20–29 ng/mL) are common in primary hyperparathyroidism (PHPT), but data regarding the vitamin D metabolism in this population is limited.AIM: The aim of this study is to estimate the vitamin D metabolites and their relationship with the main parameters of phosphorus-calcium metabolism in patients with PHPT at baseline and on the background of a single dose of cholecalciferol 150,000 IU.MATERIALS AND METHODS: A single-center interventional, dynamic, prospective, comparative study has been carried out. The study included 54 participants, divided into two groups: the 1st group included 27 patients with confirmed PHPT, the 2nd control group (n = 27), matched on gender (p = 0.062). The study included 4 visits; the baseline laboratory examination and a bolus dose of cholecalciferol were performed at the visit 1, the subsequent visits included a dynamic laboratory examination.RESULTS: Vitamin D deficiency (<20 ng/ml) was detected in 69% of patients with PHPT. In the PHPT group (before cholecalciferol therapy), there was a direct association of 1.25(OH)₂ D₃ with albumin-corrected and ionized calcium, as well as between the 25(OH)D₃ /24.25(OH)₂ D₃ ratio with PTH and magnesium. After taking of cholecalciferol, the levels of 1.25(OH)₂ D₃ and 25(OH)D₃ /24.25(OH)₂ D₃ were significantly increased, and the levels of 25(OH)D₃ /1.25(OH)₂ D₃ were significantly declined at all visits among patients with PHPT. The common 25(OH)D level was comparable to the control group, however the levels of 1,25(OH)₂ D₃ in patients with PHPT were 55% higher at baseline, and after taking of cholecalciferol 150,000 IU. They remained increased by 3–7 days by an additional 23–36%, significantly higher than those in the control group: 44%, 74% and 65%, at visits 2, 3 and 4, respectively (p<0.05). The taking of 150,000 IU cholecalciferol in the PHPT group did not lead to a significant increase in hypercalcemia and hypercalciuria, which indicates the safety of this dose in patients with mild hypercalcemia (albumin corrected calcium <3 mmol/l). None of the study participants experienced any side effects.CONCLUSION: The completely comprehensive assessment of vitamin D metabolites was carried out for the first time in patients with PHPT before and after using a bolus dose of cholecalciferol. The results confirmed the differences of vitamin D metabolism in chronic excessive secretion of PTH compared to control group, which is new data in the pathogenesis of the disease, and can be used to develop optimal regimens for cholecalciferol taking in this population.

Vitamin D-binding protein (DBP) was discovered more than half a century ago as a polymorphic serum protein and is currently characterized by a variety of physiological properties. First of all, DBP carries the bulk of vitamin D metabolites circulating in the bloodstream, while albumin is the second most important transport protein, especially in patients with a low concentration of DBP in serum. Since it was discovered that only 12% of the total circulating DBP have occupied steroid binding sites, a vigorous study of other potential biological roles of DBP was initiated: actin utilization, regulation of inflammation and innate immunity mechanisms, fatty acid binding, effects on bone metabolism and participation in the tumor pathogenesis. This review focuses on the main known biological functions of DBP.