Dataset Information

Vitamin D-binding protein levels do not influence the effect of vitamin D repletion on serum PTH and calcium: data from a randomized, controlled trial.

ABSTRACT:

Context

Vitamin D deficiency, defined by the total serum 25-hydroxyvitamin D [25(OH)D] level, is common and more prevalent among Blacks than whites. Vitamin D-binding protein (DBP) levels vary with race and may modulate "bioavailable" levels of 25(OH)D.

Objective

To determine the effect of DBP levels on the functional response to vitamin D.

Setting and design

A randomized, placebo-controlled trial of vitamin D repletion for 2 mo, which took place at an outpatient research unit. Participants included 150 vitamin D-deficient (25(OH)D <20 ng/mL) adults. Participants were randomly assigned to receive either 50,000 IU of vitamin D3 or placebo weekly for 8 weeks. This is a post-hoc analysis using DBP, 25(OH)D, PTH, and calcium levels.

Results

Blacks had lower total 25(OH)D (12 vs 15 ng/mL, P < .001) and DBP levels (119 vs 234 μg/mL, P < .001) than non-Blacks. DBP levels were similar before and after vitamin D3 or placebo treatment (r = 0.98, P < .001). Baseline total 25(OH)D levels were a significant determinant of baseline PTH levels (P < .001). The change in total 25(OH)D was associated with the change in PTH (P < 0.001) and calcium levels (P < .05). In contrast, DBP levels were not a determinant of baseline PTH (P = .57) nor significantly related to changes in either PTH (P = .53) or calcium levels (P = .88).

Conclusions

DBP levels are stable in Blacks and non-Blacks, and do not change with correction of vitamin D deficiency. Even for individuals with total 25(OH)D levels < 20 ng/mL, Blacks have significantly lower DBP levels than non-Blacks. However, within this range of total 25(OH)D, DBP levels do not influence the effect of vitamin D repletion on PTH or calcium levels.

SUBMITTER: Ponda MP

PROVIDER: S-EPMC4079311 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Vitamin D-binding protein levels do not influence the effect of vitamin D repletion on serum PTH and calcium: data from a randomized, controlled trial.

Ponda Manish P MP McGee David D Breslow Jan L JL

The Journal of clinical endocrinology and metabolism 20140408 7

<h4>Context</h4>Vitamin D deficiency, defined by the total serum 25-hydroxyvitamin D [25(OH)D] level, is common and more prevalent among Blacks than whites. Vitamin D-binding protein (DBP) levels vary with race and may modulate "bioavailable" levels of 25(OH)D.<h4>Objective</h4>To determine the effect of DBP levels on the functional response to vitamin D.<h4>Setting and design</h4>A randomized, placebo-controlled trial of vitamin D repletion for 2 mo, which took place at an outpatient research u ...[more]

PMID: 24712573

Similar Datasets

Project description:ObjectivePrevious studies have noted a specific association between type 1 diabetes and insufficient levels of vitamin D, as well as polymorphisms within genes related to vitamin D pathways. Here, we examined whether serum levels or genotypes of the vitamin D-binding protein (VDBP), a molecule key to the biologic actions of vitamin D, specifically associate with the disorder.Research design and methodsA retrospective, cross-sectional analysis of VDBP levels used samples from 472 individuals of similar age and sex distribution, including 153 control subjects, 203 patients with type 1 diabetes, and 116 first-degree relatives of type 1 diabetic patients. Single nucleotide polymorphism (SNP) typing for VDBP polymorphisms (SNP rs4588 and rs7041) was performed on this cohort to determine potential genetic correlations. In addition, SNP analysis of a second sample set of banked DNA samples from 1,502 type 1 diabetic patients and 1,880 control subjects also was used to determine genotype frequencies.ResultsSerum VDBP levels were highest in healthy control subjects (median 423.5 µg/mL [range 193.5-4,345.0; interquartile range 354.1-]586), intermediate in first-degree relatives (402.9 µg/mL [204.7-4,850.0; 329.6-492.4]), and lowest in type 1 diabetic patients (385.3 µg/mL [99.3-1,305.0; 328.3-473.0]; P = 0.003 vs. control subjects). VDBP levels did not associate with serum vitamin D levels, age, or disease duration. However, VDBP levels were, overall, lower in male subjects (374.7 µg/mL [188.9-1,602.0; 326.9-449.9]) than female subjects (433.4 µg/mL [99.3-4,850.0; 359.4-567.8]; P < 0.0001). It is noteworthy that no differences in genotype frequencies of the VDBP polymorphisms were associated with serum VDBP levels or between type 1 diabetic patients and control subjects.ConclusionsSerum VDBP levels are decreased in those with type 1 diabetes. These studies suggest that multiple components in the metabolic pathway of vitamin D may be altered in type 1 diabetes and, collectively, have the potential to influence disease pathogenesis.

Project description:IntroductionVitamin D binding protein (VDBP) plays a crucial role in vitamin D transport and metabolism. The rs4588-A polymorphism of the GC gene, encoding VDBP, has been associated with altered serum VDBP and 25-hydroxyvitamin D (25OHD) levels. However, the mechanisms underlying these effects remain unclear. We aimed to investigate the relationship between urinary VDBP excretion and serum VDBP and 25OHD levels in individuals with and without the rs4588-A allele.MethodsA cross-sectional study was conducted on 109 children (mean age: 11.96 years) to explore the impact of rs4588-A on vitamin D metabolism and urinary VDBP excretion. Biochemical analyses determined serum 25OHD and VDBP levels, and urinary VDBP-to-creatinine ratio (u-VDBP/Cr). Genotyping for rs4588 SNP was performed using LightSNiP assay. Statistical analyses included correlation, linear regression, and comparison between allele groups.ResultsParticipants carrying the rs4588-A allele exhibited lower serum 25OHD levels compared to non-carriers (median (IQR): 11.85 (3.5) vs. 12.86 (4.9), p = 0.023). However, no statistically significant differences were observed in serum VDBP levels (126.34 ± 59.3 in rs4588-A vs. 136.49 ± 51.3 in non-rs4588-A, p = 0.141) or in u-VDBP/Cr (median (IQR): 0.4 (0.35) in rs4588-A vs. 0.386 (0.43) in non-rs4588-A, p = 0.189) between the two allele groups. A significant inverse correlation between u-VDBP/Cr and serum VDBP levels was found only in rs4588-A carriers (r = -0.367, p = 0.024). No such correlation was observed in non-carriers or the entire cohort. A linear regression analysis confirmed the impact of u-VDBP/Cr on serum VDBP levels in rs4588-A carriers (B = -0.269, t = -2.185, p = 0.035).ConclusionIndividuals with the rs4588-A allele in the GC gene had lower serum 25OHD levels. An inverse correlation between urinary VDBP excretion and serum VDBP levels was observed, suggesting a partial role of the renal pathway in altered serum VDBP and 25OHD levels linked to the rs4588-A allele.

Project description:Vitamin D deficiency is common and associated with dyslipidemia. However, it is unclear whether oral vitamin D supplementation improves the lipid profile. Therefore, we conducted a randomized, placebo-controlled trial to determine the short-term effects of vitamin D repletion on the lipid profile.One hundred fifty-one vitamin D-deficient (25-hydroxyvitamin D <20 ng/mL) adults with elevated risk for cardiovascular disease were randomized to receive either 50 000 IU of vitamin D3 weekly for 8 weeks or placebo. The primary outcome was the change in small low-density lipoprotein (LDL) particle number. Secondary outcomes included changes in other nuclear magnetic resonance-based and chemical lipid fractions. Vitamin D failed to improve the lipid profile. Compared with the placebo, vitamin D repletion did not change small LDL particle number (mean change, +18 nmol/L; 95% CI [-80 to +116 nmol/L]; P=0.63). There were also no changes in the chemical lipid profile: total cholesterol (+5.8 mg/dL, 95% CI [-1.4 to +13.0 mg/dL], P=0.14); LDL cholesterol (+3.8 mg/dL, 95% CI [-2.5 to +10.2 mg/dL], P=0.13); high-density lipoprotein cholesterol (+0.4 mg/dL 95% CI [-1.6 to +2.6 mg/dL], P=0.71); and triglycerides (+7.9 mg/dL 95% CI [-6.5 to +22.3 mg/dL]). In the vitamin D repletion group, exploratory multivariate regression analysis demonstrates that changes in LDL cholesterol were positively correlated with the changes in serum calcium (P<0.001) and inversely with the changes in serum parathyroid hormone (P=0.02).In contrast to the association between low 25-hydroxyvitamin D levels and dyslipidemia, correcting vitamin D deficiency in the short-term does not improve the lipid profile. Repletion of 25-hydroxyvitamin D levels raised serum calcium levels and decreased serum parathyroid hormone levels. These expected physiological responses to vitamin D therapy were correlated with a significant increase in LDL cholesterol. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT01008384.

Dataset Information

Vitamin D-binding protein levels do not influence the effect of vitamin D repletion on serum PTH and calcium: data from a randomized, controlled trial.

Context

Objective

Setting and design

Results

Conclusions

Publications

Vitamin D-binding protein levels do not influence the effect of vitamin D repletion on serum PTH and calcium: data from a randomized, controlled trial.

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