Correlation between urine vitamin D -binding protein and early -stage renal damage in Type 2 diabetes / 中南大学学报(医学版)

OBJECTIVES@#The excretion of urinary vitamin D-binding protein (uVDBP) is related to the occurrence and development of early-stage renal damage in patients with Type 2 diabetes (T2DM). This study aims to explore the significance of detecting uVDBP in T2DM patients and its relationship with renal tubules, and to provide a new direction for the early diagnosis of T2DM renal damage.@*METHODS@#A total of 105 patients with T2DM, who met the inclusion criteria, were included as a patient group, and recruited 30 individuals as a normal control group. The general information and blood and urine biochemical indicators of all subjects were collected; the levels of uVDBP, and a marker of tubular injury [urine kidney injury molecule 1 (uKIM-1), urine neutrophil gelatinase-associated lipocalin (uNGAL) and urine retinol-binding protein (uRBP)] were detected by enzyme-linked immunosorbent assay. The results were corrected by urinary creatinine (Cr) to uVDBP/Cr, uKIM-1/Cr, uNGAL/Cr and uRBP/Cr. The Pearson's and Spearman's correlation tests were used to analyze the correlation between uVDBP/Cr and urine albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR) and markers of tubular injury, and multivariate linear regression and receiver operating characteristic curve were used to analyze the correlation between uVDBP/Cr and UACR or eGFR.@*RESULTS@#Compared with the normal control group, the uVDBP/Cr level in the patient group was increased (P<0.05), and which was positively correlated with UACR (r=0.774, P<0.01), and negatively correlated with eGFR (r=-0.397, P<0.01). There were differences in the levels of uKIM-1/Cr, uNGAL/Cr, and uRBP/Cr between the 2 groups (all P<0.01). The uVDBP/Cr was positively correlated with uKIM-1/Cr (r=0.752, P<0.01), uNGAL/Cr (r=0.644, P<0.01) and uRBP/Cr (r=0.812, P<0.01). The sensitivity was 90.0% and the specificity was 82.9% (UACR>30 mg/g) for evaluation of uVDBP/Cr on T2DM patients with early-stage renal damage, while the sensitivity was 75.0% and the specificity was 72.6% for evaluation of eGFR on T2DM patients with early-stage renal damage.@*CONCLUSIONS@#The uVDBP/Cr can be used as a biomarker in early-stage renal damage in T2DM patients.

Evaluation of Serum and Gingival Crevicular Fluid Levels of Vitamin D Binding Protein in Subjects with Clinically Healthy Periodontium and Chronic Periodontitis: A Clinico Bio-Chemical Study

Background: Advances in oral and periodontal disease diagnostic research are moving towards methods wherein periodontal risk can be identified and quantified by objective measures such as bio?markers. Given the roles of vitamin D binding protein (DBP) in modulating the immune response and in the transport of vitamin D, it is hypothesised that quantitative changes of vitamin DBP are associated with periodontal disease. Aim: The aim of the current study is to measure DBP levels in serum and gingival crevicular fluid (GCF) of patients with generalised chronic periodontitis, in comparison to healthy controls. Materials and Methods: The present cross?sectional clinico?bio?chemical study includes 30 systemically healthy subjects with 15 periodontally healthy and 15 chronic periodontitis subjects who were recruited from the out?patient Department of Periodontics. GCF and blood samples were collected from all the patients. DBP estimation was performed in both the samples using a commercially available ELISA kit. Results: Serum and GCF DBP levels in chronic periodontitis subjects were significantly higher when compared to the periodontally healthy group. There were no significant correlations found among serum and GCF DBP levels with gender and increasing age in both the groups. An increase in disease severity measured by the increase in probing pocket depth and clinical attachment loss did not show correlation with the GCF and serum DBP levels in the chronic periodontitis group. Conclusion: Based on the findings of the present study, increased serum and GCF DBP levels in chronic periodontitis seem to be a probable marker for identifying ongoing periodontal destruction.

Association of Maternal and Cord Plasma Total, Free and Bioavailable 25-Hyrodroxyvitamin D with Neonatal Anthropometric Measurements at Birth: A Preliminary Study in a Private Hospital

@#Introduction: 25-hydroxyvitamin D (25OHD) is the principal biomarker of vitamin D status. In circulation, 25OHD is primarily bound to vitamin D binding protein (VDBP), leaving a small proportion bound to albumin and as free form. Previous studies have suggested that free 25OHD is better correlated with health outcomes. However, in pregnancy where VDBP level is extremely elevated, the correlations between free 25OHD with health outcomes are far from conclusive. Here we show the associations of maternal and cord total, free and bioavailable 25OHD concurrently with neonatal anthropometric measurements in healthy pregnant mothers-neonates pairs. Method: Total 25OHD level was measured by using chemiluminescent immunoassay. Free and bioavailable 25OHD were calculated using published mathematical models. Results: The results showed that birth weight and head circumference were negatively associated with maternal total 25OHD but not significantly associated with free and bioavailable 25OHD. There were no significant associations between cord total, free and bioavailable 25OHD with any of the neonatal anthropometric measurements. Conclusion: The outcomes of this study should encourage further research in a larger sample size. Notably, future research could lead to the establishment of causative relationships and plausible mechanisms between maternal and cord 25OHD with neonatal anthropometric measurements.

Vitamin D, vitamin D binding protein, vitamin D receptor levels and cardiac dysautonomia in patients with multiple sclerosis: a cross-sectional study / Vitamina D, proteína de ligação à vitamina D, níveis de receptores de vitamina D e disautonomia cardíaca em pacientes com esclerose múltipla: um estudo transversal

ABSTRACT Vitamin D is a pleiotropic steroid hormone that modulates the autonomic balance. Its deficiency has been described as an environmental risk factor for multiple sclerosis (MS). The aim of this study was to investigate the serum levels of vitamin D, vitamin D binding protein (VDBP) and vitamin D receptors (VDR) and to evaluate cardiac dysautonomia in MS patients due to bidirectional interaction between vitamin D and the autonomic nervous system. Methods: The current cross-sectional study was conducted on 26 patients with relapsing-remitting MS and on 24 healthy controls. Twenty-four-hour ambulatory blood pressure variability (BPV) was calculated and the participants were evaluated for orthostatic hypotension and supine hypertension. Serum levels of vitamin D, VDBP and VDR were measured. Results: The mean serum vitamin D level was significantly lower in MS patients than in controls (p = 0.044); however there was no significant difference in terms of VDR and VDBP levels between the groups. Supine hypertension and orthostatic hypotension were significant and the 24-hour systolic BPV was significantly decreased in patients with MS (p < 0.05) compared to controls. No correlation was found between vitamin D, VDBP and VDR with supine hypertension, orthostatic hypotension and systolic BPV values (p > 0.05). Also, there was a negative correlation between VDBP and the EDSS (p = 0.039, r = −0.406). Conclusion: There was no correlation between orthostatic hypotension, supine hypertension and systolic BPV values and serum vitamin D, VDBP and VDR in MS patients. Future prospective studies with large number of patients may help us to better understand the relationship between vitamin D and the autonomic nervous system.

RESUMO A vitamina D é um hormônio esteroide pleiotrópico que modula o equilíbrio autonômico. Sua deficiência tem sido descrita como fator de risco ambiental para esclerose múltipla (EM). O objetivo deste estudo foi investigar os níveis séricos de vitamina D, proteína de ligação à vitamina D (VDBP) e receptor de vitamina D (VDR) e avaliar a disautonomia cardíaca em pacientes com EM devida à interação bidirecional entre vitamina D e sistema nervoso autônomo. Métodos: O presente estudo transversal foi realizado em 26 pacientes com EM remitente-recorrente e em 24 controles saudáveis. A variabilidade da pressão arterial ambulatorial (BPV) por 24 horas foi calculada e os participantes foram avaliados quanto à hipotensão ortostática e hipertensão supina. Os níveis séricos de vitamina D, VDBP e VDR foram medidos. Resultados: O nível sérico médio de vitamina D foi significativamente menor nos pacientes com EM do que nos controles (p = 0,044); no entanto, não houve diferença significativa em termos de níveis de VDR e VDBP entre os grupos. Hipertensão supina e hipotensão ortostática foram significativas e a BPV sistólica de 24 horas diminuiu significativamente em pacientes com EM (p < 0,05) em comparação aos controles. Não foi encontrada correlação entre vitamina D, VDBP e VDR com hipertensão supina, hipotensão ortostática e BPV sistólica (p > 0,05). Também houve correlação negativa entre VDBP e EDSS (p = 0,039, r = −0,406). Conclusão: Não houve correlação entre hipotensão ortostática, hipertensão supina e valores de BPV sistólica e vitamina D sérica, VDBP e VDR em pacientes com EM. Futuros estudos prospectivos com grande número de pacientes podem nos ajudar a entender melhor a relação entre vitamina D e sistema nervoso autônomo.

Research on the vitamin D binding protein gene polymorphism in elderly patients with stable chronic obstructive pulmonary disease / 中华老年医学杂志

Objective@#To discuss the correlation between the effect of vitamin D treatment and vitamin D binding protein gene polymorphism in elderly patients with stable chronic obstructive pulmonary disease(COPD).@*Methods@#A total of 800 elderly patients with stable COPD admitted to the four Departments of Respiratory Medicine of four Wenzhou Hospitals were enrolled from September 2016 to November 2018.Because of the drop-out during follow-up, there were final 776 patients in our prospective research.According to the GC gene type, patients were divided into the GC1F-1S(n=214), the GC1F-1S(n=168), GC1F-2(n=160), GC1S-1S(n=132), GC1F-2(n=82)and GC2-2 groups(n=44), and each group was randomly divided into control group(n=400)receiving the conventional treatment and the treatment group(n=400)taking vitmain D 0.5 μg/d for 3 months as add-on to the conventional treatment.The lung function and the COPD assessment test(CAT)score before and after the therapy were observed and compared in patients with different GC sub-genotypes.@*Results@#Among the elderly patients enrolled in our research, GC1F-1F genotype was most common, accounting for 26.8%(214 cases), the followings of next order were GC 1F-1S genotype accounting for 21.0%(168 cases), and GC2-2 genotype was most rare, accounting for 5.5%(44 cases). The lung function were improved and the CAT score were reduced in all groups after therapy as compared with pre-treatment(P<0.05). The lung function was better and the CAT score was lower in patients with GC1F-1F, GC1F-1S, GC1F-2, GC1S-1S sub-genotypes(13.77±4.67 vs.15.83±3.73, 15.38±4.45 vs.17.86±3.92, 17.42±3.19 vs.19.46±4.07)than in the corresponding control subgroups after treatment(P<0.05). While, there was no significant difference in the lung function and the CAT score between patients with GC1S-2 and GC2-2 genotypes in control versus treatment subgroups(P>0.05).@*Conclusions@#Vitamin D binding protein gene polymorphism is associated with the curative effect of supplement of vitamin D in elderly patients with stable COPD, which has a predictive value for the curative effect of vitamin D supplement.

Research on the vitamin D binding protein gene polymorphism in elderly patients with stable chronic obstructive pulmonary disease / 中华老年医学杂志

Objective To discuss the correlation between the effect of vitamin D treatment and vitamin D binding protein gene polymorphism in elderly patients with stable chronic obstructive pulmonary disease(COPD).Methods A total of 800 elderly patients with stable COPD admitted to the four Departments of Respiratory Medicine of four Wenzhou Hospitals were enrolled from September 2016 to November 2018.Because of the drop-out during follow-up,there were final 776 patients in our prospective research.According to the GC gene type,patients were divided into the GC1F-1S(n=214),the GC1F-1S(n=168),GC1F-2 (n=160),GC1S-1S(n=132),GC1F-2(n=82)and GC2-2 groups(n=44),and each group was randomly divided into control group(n=400)receiving the conventional treatment and the treatment group(n=400)taking vitmain D 0.5 μg/d for 3 months as add-on to the conventional treatment.The lung function and the COPD assessment test(CAT)score before and after the therapy were observed and compared in patients with different GC sub-genotypes.Results Among the elderly patients enrolled in our research,GClF-1F genotype was most common,accounting for 26.8％ (214 cases),the followings of next order were GC 1F-1S genotype accounting for 21.0％ (168 cases),and GC2-2 genotype was most rare,accounting for 5.5 ％ (44 cases).The lung function were improved and the CAT score were reduced in all groups after therapy as compared with pre-treatment(P＜0.05).The lung function was better and the CAT score was lower in patients with GC1F-1F,GC1F-1S,GC1F-2,GC1S-1S sub-genotypes(13.77±4.67 vs.15.83±3.73,15.38±4.45 vs.17.86 ± 3.92,17.42 ± 3.19 vs.19.46 ± 4.07) than in the corresponding control subgroups after treatment (P ＜ 0.05).While,there was no significant difference in the lung function and the CAT score between patients with GC1S-2 and GC2-2 genotypes in control versus treatment subgroups(P＞0.05).Conclusions Vitamin D binding protein gene polymorphism is associated with the curative effect of supplement of vitamin D in elderly patients with stable COPD,which has a predictive value for the curative effect of vitamin D supplement.

The clinical significance of serum 25-hydroxy vitamin D and vitamin D binding protein in premature infants with bronchopulmonary dysplasia / 中国新生儿科杂志

Objective To study the relationship of serum 25-hydroxy vitamin D [25-(OH) D] and vitamin D binding protein (DBP) in premature infants with bronchopulmonary dysplasia (BPD) and their clinical significance.Method From March 2017 to September 2018,the premature infants with gestational age (GA)＜32 weeks admitted to the neonatal department of our hospital were prospectively studied.All the premature infants were given 800 IU/d vitamin D supplement from one week after birth.Venous blood sample were collected at birth and 28 d after birth to measure 25-(OH) D aud DBP levels.The infants were evaluated for BPD at 28 d after birth and then assigned into the BPD group and the non-BPD group.The differences of 25-(OH) D and DBP levels were compared.Result A total of 170 premature infants (GA＜32 weeks) were included,including 56 cases in the BPD group and 114 cases in the non-BPD group.The BPD group had 34 males,the GA was (29.8±1.2) weeks,the birth weight (BW) was (1 198± 157) g.The non-BPD group had 95 males,the GA was (30.2± 1.5) weeks,the BW was (1 243± 146) g.No significant differences existed in GA,BW and male gender proportion between BPD group and non-BPD group (P＞0.05).The BPD group had a lower levels of serum 25-(OH) D at birth [(27.8±5.9) nmol/L vs.(30.4±1.1) nmol/L,P＜0.05].The levels of serum 25-(OH) D in moderate/severe BPD group were significantly lower than mild BPD group [(25.3±4.9) nmol/L vs.(29.7±5.9) nmol/L,P＜0.05];25-(OH) D in BPD group was still lower than the non-BPD group at 28 days after birth (after vitamin D supplement) [(77.5±11.7) nmol/L vs.(83.8±11.6) nmol/L,P＜0.05].Comparison of serum DBP levels between the two groups showed that,DBP at 28 d after birth in BPD group were significantly lower than the non-BPD group,and DBP in moderate/severe BPD group were significantly lower than the mild BPD group [(373.9± 19.1) μg/ml vs.(391.4±23.6) μg/ml],the differences were both statistically significant (P＜0.05).Multivariate analysis showed that the high serum 25-(OH)D level at birth (OR=0.827,95％CI0.693～0.987) was protective factors for BPD,while neonatal pneumonia (OR=4.331,95％CI 1.269～14.784) and neonatal sepsis (OR=4.020,95％CI 1.153～14.015) were risk factors for BPD.Conclusion The high serum 25-(OH) D level at birth in preterm infants was protective factors for BPD,while neonatal pneumonia and sepsis were the risk factors for BPD.Moreover,low serum 25-(OH) D level at birth and low serum DBP level at 28 d after birth maybe useful indicators for the severity of BPD.

Differences in 25-hydroxy vitamin D and vitamin D-binding protein concentrations according to the severity of endometriosis / 대한생식의학회지

OBJECTIVE: To investigate serum 25-hydroxyl vitamin D (25(OH)D) and vitamin D-binding protein (VDBP) concentrations in women with endometriosis according to the severity of disease. METHODS: Women with mild endometriosis (n = 9) and advanced endometriosis (n = 7), as well as healthy controls (n = 16), were enrolled in this observational study. Serum total 25(OH)D concentrations were analyzed using the Elecsys vitamin D total kit with the Cobas e602 module. Concentrations of bioavailable and free 25(OH)D were calculated. Concentrations of VDBP were measured using the Human Vitamin D BP Quantikine ELISA kit. Variables were tested for normality and homoscedasticity using the Shapiro-Wilk test and Leven F test, respectively. Correlation analysis was used to identify the variables related to total 25(OH)D and VDBP levels. To assess the effects of total 25(OH)D and VDBP levels in the three groups, multivariate generalized additive modeling (GAM) was performed. RESULTS: Gravidity and parity were significantly different across the three groups. Erythrocyte sedimentation rate (ESR) and CA-125 levels increased as a function of endometriosis severity, respectively (p= 0.051, p= 0.004). The correlation analysis showed that total 25(OH)D levels were positively correlated with gravidity (r = 0.59, p< 0.001) and parity (r = 0.51, p< 0.003). Multivariate GAM showed no significant relationship of total 25(OH)D levels with EMT severity after adjusting for gravidity and ESR. However, the coefficient of total 25(OH)D levels with gravidity was significant (1.87; 95% confidence interval, 0.12–3.63; p= 0.040). CONCLUSION: These results indicate that vitamin D and VDBP levels were not associated with the severity of endometriosis.

Analysis of vitamin D-binding protein (VDBP) gene polymorphisms in Korean women with and without endometriosis / 대한생식의학회지

OBJECTIVE: Vitamin D-binding protein (VDBP) mediates various biological processes in humans. The goal of this study was to investigate whether VDBP gene polymorphisms could predispose Korean women to endometriosis. METHODS: We prospectively enrolled women with endometriosis (n = 16) and healthy controls (n = 16). Total serum 25-hydroxyl vitamin D (25(OH)D) concentrations were measured using an Elecsys vitamin D total kit. Levels of bioavailable and free 25(OH)D were calculated. Concentrations of VDBP were measured using a vitamin D BP Quantikine ELISA kit. DNA was extracted using a DNeasy blood & tissue kit. Two single-nucleotide polymorphisms (SNPs; rs4588 and rs7041) in GC, the gene that codes for VDBP, were analyzed using a TaqMan SNP genotyping assay kit. The functional variant of VDBP was determined based on the results of the two SNPs. RESULTS: Gravidity and parity were significantly lower in the endometriosis patients than in the control group, but serum CA-125 levels and the erythrocyte sedimentation rate were significantly higher. Total serum 25(OH)D levels in the endometriosis patients were significantly lower than in the control group. However, serum bioavailable 25(OH)D, free 25(OH)D, and VDBP levels did not differ significantly between the endometriosis and control groups. The genotypes and allele frequencies of GC were similar in both groups. CONCLUSION: Korean women with endometriosis had lower total serum 25(OH)D concentrations than controls. Neither serum VDBP concentrations nor polymorphisms in the gene coding for VDBP were associated with endometriosis. Further studies are needed to investigate the pathophysiology and clinical implications of 25(OH)D and VDBP in endometriosis.

Changes of 25-hydroxy vitamin D and vitamin D binding protein in critically ill chidren and its clinical significance / 中国小儿急救医学

Objective To investigate the 25-hydroxy-vitamin D[25(OH)D] and vitamin D binding protein ( VBDP) levels in critically ill children admitted to PICU,their clinical significance and the relation-ship with prognosis. Methods Two hundred and ninty-five children with critical illness admitted to PICU from February 2015 to July 2016 were enrolled as subjects( study group) and 44 healthy controls were recrui-ted. Serum 25(OH)D and VDBP levels were measured on the 1st and 7th day of PICU,then clinical data were collected for statistical analysis. Results (1) Among subjects,there were no statistically significant differ-ences in the incidences of 25(OH)D deficiency and VDBP decline(P>0. 05). (2)The levels of 25 (OH)D and VDBP in the study group were lower than those in the control group [ ( 61. 38 ± 29. 42 ) nmol/L vs. (97. 11 ± 30. 11) nmol/L; (514. 36 ± 211. 13)μmol/L vs. (840. 82 ± 448. 96)μmol/L,respectively,P <0. 05]. (3) There were no significant differences in the level of VDBP ,28-day mortality,organ failure rate and mechanical ventilation rate among 25(OH)D adequate group(n=85),inadequate group(n=97) and deficient group( n=113 ) ( P>0. 05 ) . The duration of PICU stay,PRISMⅢscores were significantly longer and higher (P<0. 05) in 25(OH)D inadequate group or deficient group than those of 25(OH)D adequate group.(4) Compare to the 7th day ,the levels of 25(OH)D and VDBP were lower (P <0.05) and PRISM Ⅲscores was higer on the 1st day in the cases staying in PICU≥7 d[ (71. 14 ± 31. 78)nmol/L vs. (60.65 ±30.77)nmol/L;(532.23 ±148.49)μmol/L vs. (484.73 ±128.17)μmol/L;2.0(0.0 ～5.0) scores vs. 5. 0(3. 0～8. 0)scores,respectively,P<0. 05]. (5) Among the 295 cases of critically ill children ,the 28-day mortality was 12. 9％(38/295),the death patients showed lower 25(OH)D status[ (51. 17 ± 29.65)nmol/L vs. (62.89 ±29.15)nmol/L,P <0.05] and higher PRISM Ⅲ score[ 8.5(5.0 ～14.3) scores vs. 4. 0(1. 0～7. 0) scores,P<0. 05 ]than those of the survival. Conclusion (1)The prevalences of 25(OH)D and VDBP insufficient and deficiency among critically ill children are high. (2) Patients with 25(OH)D insufficiency and deficiency show a poorer prognosis than those with sufficient 25(OH)D. (3) The change of 25(OH)D status is not completely consistent with the VDBP.

Clinical study of serum vitamin D binding protein in patients with rheumatoid arthritis associated with secondary osteoporosis / 中华风湿病学杂志

Objective To explore the changes of serum vitamin D binding protein (VDBP) levels in patients with rheumatoid arthritis (RA) and the clinical significance of association between serum VDBP with secondary osteoporosis (OP) in RA.Methods One hundred and sixty patients with RA were enrolled in the study.Eighty-three normal subjects were recruited as the control group.The concentration of serum VDBP was determined by enzyme-linked immuno sorbent assay (ELISA),and bone mineral density (BMD) was measured by dual energy X-ray absorptiometry.Clinical and laboratory indexes of RA patients were recorded in detail and disease activity (DAS28) score,health assessment questionnaire (HAQ) and Sharp score according to X-ray examination of both hands were calculated simultaneously.The t test was used to compare the metrological data between the two groups,and the x2 test was used to compare the intergroup rate.The correlation analysis was tested by Pearson correlation analysis,the ROC curve was used to analyze the threshold of the serum VDBP,and the multivariate logistic regression analysis was used for multivariate analysis.Results ① Serum levels of VDBP in RA patients were higher than that in control group [(414±12) ng/ml vs (79±12) ng/ml,t=20.082,P＜0.01].Positive rate of serum levels of VDBP was 67.0％(118/176) in RA patients,which was higher than that in the control group (4.8％)(x2 =87.651,P＜0.01).② The threshold of serum VDBP levels for diagnosing RA was 193.74 ng/ml (AUC=0.943,Youden index=0.796,P＜0.01).③ DAS28 sore in group with positive VDBP was significantly higher than that in group with negative VDBP (P9=0.025).There was significant difference regarding on the incidence of OP in female RA patients between groups with positive and negative VDBP [41.9％(54/129) vs 31.8％(14/44),x2=4.325,P=0.038].④ Linear correlation analysis found that DAS28in RA patients was positively correlated with serum VDBP levels (r=0.252,P=0.019).And anti-CCP was negatively correlated with serum VDBP levels (r=-0.150,P=0.049).⑤ Results of logistic regression analysis showed that sex [OR=9.841,95％CI (1.349,71.810),P=0.024],age [OR=1.154,95 ％CI (1.069,1.245),P＜0.01] and Sharp score [OR=1.102,95％CI (1.002,1.021),P=0.018] were risk factors for OP in RA patients.Conclusion Serum VDBP levels are significantly higher in patients with RA.Meanwhile,serum VDBP levels are correlated with disease activity and secondary OP in RA.

Clinical investigation of relationship between serum 25-hydroxyvitamin D3 and urine vitamin D binding protein levels in patients with diabetic nephropathy / 中国基层医药

Objective To investigate the serum levels of 25-hydroxyvitamin D3 (25 (OH)D3) and urine vitamin D binding protein(uVDBP) in patients with diabetic nephropathy (DN),and to determine the relationship between 25 (OH) D3,uVDBP and DN,in order to provide a new method for early diagnosis and treatment of DN.Methods From January 2015 to December 2015,85 DN patients admitted into Weihai Municipal Hospital were selected.According to the ratio of UALB to UCR(UACR),the patients were divided into three groups.Type 2 diabetes had 28 cases of normal albuminuria group,31 cases of microalbuminuria group,and 26 cases of clinical albuminuria group.We also enrolled 25 healthy people who received outpatient service as control group.Serum 25 (OH) D3 levels were measured by chemiluminescence method.Urine VDBP levels were assayed by ELISA.FPG,HbA1 c,UREA,SCr,TC,TG were measured by electrochemiluminescence.Results The results showed that serum 25 (OH)D3 was significantly lower in the normal albuminuria group,microalbuminuria group and clinical proteinuria group than that in the control group (P ＜ 0.05),and there was statistically significant difference among the four groups [(20.04 ± 7.52) ng/mL,(16.54 ± 6.51) ng/mL,(10.77 ± 4.63) ng/mL,(29.65 ± 5.47) ng/mL,F =86.294,P ＜ 0.001].The results showed that uVDBP was significantly higher in the DN group than that in the control group(all P ＜ 0.05),and there was statistically significant difference among the four groups [(8.44 ± 3.20) mg/L,(14.22 ± 3.26) mg/L,(2 1.77 ± 5.87) mg/L,(4.95 ± 1.34) mg/L,F =125.583,P ＜ 0.001].Correlation analysis showed that serum 25 (OH) D3 decreased gradually with the increase of DN and negatively correlated with UACR (r =-0.575,P ＜ 0.01),while uVDBP level was positively correlated with UACR (r =0.436,P =0.015).Conclusion With the progress of DN,serum 25 (OH) D3 levels gradually decreased,indicating that 25 (OH) D3 may play an important role in the pathogenesis of DN;uVDBP may be an early diagnostic method for DN.

Calculation of free and bioavailable vitamin D and its association with bone mineral density in Malaysian women with rheumatoid arthritis

@#Introduction: Low 25-hydroxyvitamin D [25(OH)D] levels have not been consistently associated with bone mineral density (BMD). It has been suggested that calculation of the free/bioavailable 25(OH)D may correlate better with BMD. We examined this hypothesis in a cohort of Malaysian women. Materials and Methods: A cross-sectional study of 77 patients with rheumatoid arthritis (RA) and 29 controls was performed. Serum 25(OH)D was measured using the Roche Cobas E170 immunoassay. Serum vitamin D binding protein (VDBP) was measured using a monoclonal enzymelinked immunosorbent assay (ELISA). Free/bioavailable 25(OH)D were calculated using both the modified Vermuelen and Bikle formulae. Results: Since there were no significant differences between RA patients and controls for VDBP and 25(OH)D, the dataset was analysed as a whole. Calculated free 25(OH)D by Vermeulen was strongly correlated with Bikle (r = 1.00, p < 0.001). A significant positive correlation was noted between measured total 25(OH)D with free/bioavailable 25(OH) D (r = 0.607, r = 0.637, respectively, p < 0.001). Median free/bioavailable 25(OH)D values were significantly higher in Chinese compared with Malays and Indians, consistent with their median total 25(OH)D. Similar to total 25(OH)D, the free/bioavailable 25(OH)D did not correlate with BMD. Conclusion: In this first study of a multiethnic female Malaysian population, free/bioavailable 25(OH)D were found to reflect total 25(OH)D, and was not superior to total 25(OH)D in its correlation with BMD. Should they need to be calculated, the Bikle formula is easier to use but only calculates free 25(OH)D. The Vermuelen formula calculates both free/bioavailable 25(OH)D but is more complex to use.

Clinical Utility of Measurement of Vitamin D-Binding Protein and Calculation of Bioavailable Vitamin D in Assessment of Vitamin D Status

BACKGROUND: The associations of vitamin D deficiency with various clinical conditions highlighted the importance of vitamin D testing. Currently, clinicians measure only the total 25-hydroxyvitamin D [25(OH)D] concentration, regardless of its bioavailability. We aimed to determine the effect of vitamin D-binding protein (VDBP) on 25(OH)D bioavailability. METHODS: Serum samples were collected from 60 healthy controls, 50 pregnant women, and 50 patients in intensive care units (ICUs). Total 25(OH)D was quantified by liquid chromatography with tandem mass spectrometry, and VDBP levels were determined by using an ELISA kit (R&D Systems, USA). The bioavailable 25(OH)D levels were calculated by using total 25(OH)D, VDBP, and albumin concentrations. RESULTS: In comparison with healthy controls, the total 25(OH)D concentration was significantly lower in ICU patients (median, 11.65 vs 18.25 ng/mL; P<0.00001), but no significant difference was noted between pregnant women (18.25 ng/mL) and healthy controls. The VDBP level was significantly lower in ICU patients (95.58 vs 167.18 µg/mL, P=0.0002) and higher in pregnant women (225.01 vs 167.18 µg/mL, P=0.008) compared with healthy controls. Nonetheless, the calculated bioavailable 25(OH)D levels of ICU patients and pregnant women were significantly lower than those of healthy controls (1.97 and 1.93 ng/mL vs 2.56 ng/mL; P=0.0073 and 0.0027). CONCLUSIONS: A single marker of the total 25(OH)D level is not sufficient to accurately evaluate vitamin D status, especially in pregnant women. In cases where VDBP concentrations may be altered, VDBP measurements and bioavailable 25(OH)D calculations may help to determine vitamin D status accurately.

A lack of association between vitamin D-binding protein and 25-hydroxyvitamin D concentrations in pediatric type 1 diabetes without microalbuminuria

PURPOSE: Vitamin D deficiency is reported to be more common in type 1 diabetes patients and might be associated with the increased urinary loss of vitamin D binding protein (VDBP) consequent to impaired 25-hydroxyvitamin D (25(OH)D) circulation. We aimed to evaluate the possible increased urinary loss of VDBP, a correlation between VDBP and circulating 25(OH)D level, and risk factors influencing low vitamin D level in pediatric type 1 diabetes patients without microalbuminuria. METHODS: This is a cross-sectional study of subjects who visited Seoul National University Children’s Hospital between January and March 2013. Forty-two type 1 diabetes patients and 29 healthy controls were included. Biochemical parameters including serum and urine VDBP concentrations were analyzed. RESULTS: There was no significant difference in the frequency of vitamin D deficiency or serum 25(OH)D level between the 2 groups. The serum and urine VDBP concentrations did not show any difference between the 2 groups. Serum 25(OH) D level did not correlate with serum or urine VDBP. Multivariate regression analysis revealed that daylight outdoor hours (β=2.948, P=0.003) and vitamin D intake (β=2.865, P=0.003) affected the 25(OH)D level; the presence of type 1 diabetes or urinary VDBP excretion was not significant. CONCLUSIONS: In pediatric type 1 diabetes patients, urinary VDBP excretion did not contribute to low serum 25(OH)D level in the setting of normoalbuminuria. The factors associated with 25(OH)D level during winter periods were daylight outdoor hours and vitamin D intake. Further studies including both micro- and macroalbuminuria patients with type 1 diabetes are warranted.

Actin Scavenging System and Coagulation-fibrinolytic System in Peripheral Blood of Pre-eclampsia Patients / 中国医科大学学报

Objective To detect the levels of plasma gelsolin(GSN),vitamin D binding protein(VDBP)and coagulation?related parameters in peripheral blood between pre?eclampsia,then analyze their relationships with the onset or development of pre?eclampsia. Methods A total of 30 women with severe pre?eclampsia(SPE)and 30 women with mild pre?eclampsia(MPE)were enrolled for the study and randomly chosen as trial group. 30 normal pregnancies with matching gestational ages were selected as control group?1 and 30 normal full?term pregnancies were randomly chosen as control group?2. The levels of GSN,VDBP,platelet(PLT),prothrombin time(PT),thrombin time(TT),activated partial thromboplas?tin time(APTT),fibrinogen(FIB),and D?dimer were compared between those groups. Results The levels of GSN,VDBP and PLT,PT,APTT, FIB in SPE group were significantly lower than that of MPE group(P0.05). There were no statistical difference among all the levels of coagulation?related parameters in healthy pregnant women(P>0.05). Conclusion GSN and VDBP levels in pre?eclampsia are significantly lower than that of normal pregnant women,along with pathological hy?percoagulative state,and which are related to severity of disease.

Changes in serum and urine vitamin D binding protein concentrations in type 2 diabetes / 中华内分泌代谢杂志

Objective To determine the changes in serum and urine vitamin D binding protein ( VDBP) concentrations in type 2 diabetes, and to explore the clinical significance. Methods The serum and urine VDBP concentrations in 102 healthy individuals and 106 type 2 diabetic patients were determined by ELISA. For analysis and comparison, 106 type 2 diabetic patients were divided into imperfect glycemic control subgroup and perfect glycemic control subgroup, microalbuminuria subgroup and normal albuminuria subgroup. Results The cut-off point of serum VDBP concentrations was 60. 6 μg/ ml and the cut-off point of the urine ratio of VDBP and creatinine was 7. 76 mg/ g, and both were determined according to the upper limit of 97. 5 % credit intervals in 110 healthy individuals. Serum VDBP concentration and the urine ratio of VDBP to creatinine in type 2 diabetic patients were significantly higher than those in the healthy individuals ( P < 0. 01 ), the imperfect glycemic control subgroup had higher serum VDBP concentrations and the urine ratio of VDBP to creatinine than those in the perfect glycemic control subgroup ( P <0. 05). The microalbuminuria subgroup had higher urine ratio of VDBP to creatinine than that in the normal albuminuria subgroup ( P<0. 01). Urine ratio of VDBP to creatinine in diagnosing early diabetic nephropathy had sensitivity of 96. 4 % , specificity of 68 % , and concordance of 83% . Conclusion Detection of serum VDBP levels has some reference value in understanding the state of diabetes. Combined determinations of urine ratio of VDBP to creatinine and ratio of albumin to creatinine have significant clinical value in the early diagnosis of diabetic nephropathy.

Relationship between vitamin D,VDBP,VDR and asthma in children / 国际儿科学杂志

More and more studies have indicated that the relationship between vitamin D pathway and asthma,and the mechanisms include multiple abnormal aspects of vitamin D pathway leading to abnormal em-bryonic development and immune system disorders and so on. This review summarizes the relationship between vitamin D,vitamin D binding protein,vitamin D receptors,related gene polymorphisms and the immune system to describe the pathogenesis of asthma.

The research advance of the relationship between vitamin D binding protein and cancer / 中华检验医学杂志

Vitamin D binding protein ( VDBP) is a multi-functional plasma globulin which binds to the vitamin D ( VD) in the circulation system and transporting the latter to various effective organs to exert its biological functions .Studies have found that VD and its carrier VDBP are associated with the risk of various cancers such as breast cancer , prostate cancer , and colorectal cancer however , lacking sufficient epidemiological evidences so far .Furthermore , it is still controversial regarding how VD controls and affects cancer progression.In addition, studies have also demonstrated that VDBP derived macrophage-activating factor (GcMAF) is a potent lymphokine in cancer treatment .Nonetheless, the relationship between VDBP and cancer including the VDBP polymorphism, VDBP plasma concentration are still unclear; more studies are needed to further uncover its role in cancer development and progression , thus providing new evidences for cancer diagnosis, treatment, and prognosis.

The correlation of vitamin D level and vitamin D-binding protein gene polymorphism in chronic obstructive pulmonary disease / 中华内科杂志

Objective To assess the correlation of serum 25-hydroxyvitamin D (25-OHD) levels with vitamin D-binding protein (the group-specific component,GC) gene polymorphism in chronic obstructive pulmonary disease (COPD).Methods In a cross-sectional case-control study,250participants,including 116 COPD patients with smoking history and 134 healthy smokers,were investigated.A questionnaire about smoking history,vitamin D intake and comorbidities was collected.General pulmonary function was done by routine.Serum 25-OHD levels were detected by ELISA.The genetic variants (rs4588and rs7041) were genotyped by real time fluorescence polymerase chain reaction (RT-PCR) with TaqMan probe technology.Results The COPD patients had lower serum vitamin D level than the smoker subjects (36.58 nmol/L vs 43.80 nmol/L,P ＜0.001).In the COPD patients,vitamin D level was 39.43 nmol/L in those with percentage of predicted forced expiratory volume in 1 second (FEV1 ％ pred) greater than or equal to 80％.In other groups with FEV1 ％ pred 50％-80％,30％-50％ and lower than 30％,vitamin D levels were 35.32 nmol/L,32.21 nmol/L,26.25 nmol/L respectively (P ＜ 0.01).Moreover,there was a significant relevance of 25-OHD levels with FEV1 ％ pred in both COPD patients and healthy smokers (r2 =1.911; P ＜0.000 1).The mean 25-OHD concentration had a negative correlation with Global Initiative for Obstructive Lung Disease (GOLD) stages.Homozygous carriers of vitamin D-binding protein gene rs7041 T allele were independently related to 25-OHD levels and susceptibility of COPD (P ＜ 0.01 ; OR =2.140,95％ CI 1.157-3.959,P =0.015 respectively).Conclusions Patients with COPD are at high risk of vitamin D deficiency and the severity of COPD is inversely correlated with vitamin D levels.Furthermore,homozygous carrier of rs7041 T allele influences 25-OHD serum levels and is related to susceptibility of COPD,which may be a potential candidate gene for screening COPD.