Role of Vitamin D in the Onset,Progression, and Severity of Multiple Sclerosis

ObjectiveTo review and assess the role of vitamin D in the onset, progression, and relapse of multiple sclerosis (MS), based on evidence acquired from the analysis of preclinical, observational, and interventional studies.MethodsAll English language literature in MEDLINE (January 1969 through April 2012) was searched for observational and interventional studies on the dosage effect of vitamin D on the onset, progression, and relapse rate of MS. The medical subject heading (MeSH) terms used in the search included Vitamin D and Multiple Sclerosis. Additional publications and abstracts were identified from review articles and from the references cited in the previously found articles. In addition to the experimental studies, only those human studies that specified the population size, doses of vitamin D used, and the resulting effect on MS were considered.ResultsVitamin D deficiency is very common among MS patients. Multiple preclinical studies have shown that vitamin D is a potent regulator of inflammation in MS. Most observational studies support an association between high vitamin D levels and a reduced risk of developing MS. However, conflicting results have been reported by observational studies on the correlation between vitamin D and MS severity and by interventional studies using vitamin D as a therapeutic agent for MS.ConclusionVitamin D deficiency in MS patients should be avoided. In addition, the risk of developing MS might be reduced by maintaining optimal vitamin D levels in the healthy population. Larger randomized interventional trials are needed to clarify the therapeutic effect of vitamin D in MS. (Endocr Pract. 2013;19:129-136)     

The Association of Vitamin D Receptor Polymorphisms with Multiple Sclerosis in a Case-Control Study from Kuwait

Vitamin D deficiency is associated with several diseases including multiple sclerosis (MS). Several factors influence vitamin D levels and its optimal multi-function maintenance. Our objective was to assess quantifiable variables influencing vitamin D level and metabolism in MS patients from Kuwait. In a case-control study involving 50 MS patients, and 50 healthy control individuals for which plasma vitamin D levels, supplement use, vitamin D receptor (VDR) variants, and skin pigmentation indices were ascertained; we found overall vitamin D levels to be deficient in both groups, and supplement use to be common practice. VDR variants TaqI and BsmI associated with MS risk, and ApaI associated with low disease progression. VDR variant FokI associated with higher vitamin D levels in both groups. We conclude that several quantifiable variables related to vitamin D associate with MS suggesting a possible clinical immuno-modulatory application of vitamin D for MS patients in Kuwait.     

Associations of cholesterol and vitamin D metabolites with the risk for development of high grade colorectal cancer

BackgroundVitamin D deficiency is repeatedly reported in colorectal cancer (CRC). Since cholesterol and vitamin D share common precursor 7-dehydrocholesterol (7-DHC), it would be important to explore the associations of key vitamin D metabolites and serum lipid parameters in patients with high and low grade CRC. The aim of this study was to analyze relationships between serum 25(OH)D3, 24,25(OH)2D3 and 7-DHC levels and serum lipids in patients with CRC, and to evaluate their potential for prediction of risk for development of high grade CRC.MethodsWe recruited 82 patients CRC and 77 controls. 7-DHC, 25(OH)D3 and 24,25(OH)2D3 were quantified by LC-MS/MS methods.Results7-DHC, 25(OH)D3 and vitamin D metabolic ratio (VDMR) were significantly lower in CRC patients than in control group (P<0.001, P<0.010, P<0.050 and P<0.050, respectively). 25(OH)D3 levels were higher in patients with grade I CRC when compared to grade II (P<0.050). All vitamin D metabolites positively correlated with total cholesterol (TC) concentration in CRC patients. 25(OH)D3 was significant predictor of increased CRC risk (P<0.010). After adjustment for TC concentration, 25(OH)D3 lost its predictive abilities. However, 25(OH)D3 remained significant predictor of poorly differentiated type of cancer (P<0.050).ConclusionsWe found significant positive association between vitamin D status and serum total cholesterol. Although low 25(OH)D3 was found to be a significant risk factor for CRC development, the obtained results primarily suggest profound impact of cholesterol level on vitamin D status in CRC. However, our results suggest that low 25(OH)D3 might independently contribute to development of poorly differentiated tumor.     

脂溶性维生素A、D、E与妊娠期糖尿病的相关性分析

目的:探讨妊娠期糖尿病(gestational diabetes mellitus,GDM)孕妇血清中维生素A、25-羟基维生素D、维生素E的水平及其临床意义。方法:选取在大连大学附属中山医院就诊并诊断为GDM的孕妇1000例为实验组;另选取无GDM孕妇1000例为对照组。采用反向高频液相色谱荧光法(high-performance liquid chromatography,HPLC)测定其血清维生素A、E水平;高效液相色谱液相色谱串联质谱法(high-performance liquid chromatography tandem mass spectrometer,HPLC-AS/MS)测定血清25-羟基维生素D水平。结果:GDM孕妇血清中维生素A水平与无GDM孕妇比较差异无统计学意义(P>0.05);GDM孕妇血清25-羟基维生素D水平明显低于对照组(P<0.05);GDM孕妇血清维生素E水平明显高于对照组(P<0.05)。GDM孕妇血清25-羟基维生素D水平与血清维生素E水平呈显著负相关(r=-0.351,P<0.05)。结论:GDM孕妇血清25-羟基维生素D水平低,维生素E水平高,且两者有一定相关性,可能共同参与了GDM的发生。     

Vitamin D levels and risk of type 1 diabetes: A Mendelian randomization study

BackgroundVitamin D deficiency has been associated with type 1 diabetes in observational studies, but evidence from randomized controlled trials (RCTs) is lacking. The aim of this study was to test whether genetically decreased vitamin D levels are causally associated with type 1 diabetes using Mendelian randomization (MR).Methods and findingsFor our two-sample MR study, we selected as instruments single nucleotide polymorphisms (SNPs) that are strongly associated with 25-hydroxyvitamin D (25OHD) levels in a large vitamin D genome-wide association study (GWAS) on 443,734 Europeans and obtained their corresponding effect estimates on type 1 diabetes risk from a large meta-analysis of 12 type 1 diabetes GWAS studies (Ntot = 24,063, 9,358 cases, and 15,705 controls). In addition to the main analysis using inverse variance weighted MR, we applied 3 additional methods to control for pleiotropy (MR-Egger, weighted median, and mode-based estimate) and compared the respective MR estimates. We also undertook sensitivity analyses excluding SNPs with potential pleiotropic effects. We identified 69 lead independent common SNPs to be genome-wide significant for 25OHD, explaining 3.1% of the variance in 25OHD levels. MR analyses suggested that a 1 standard deviation (SD) decrease in standardized natural log-transformed 25OHD (corresponding to a 29-nmol/l change in 25OHD levels in vitamin D–insufficient individuals) was not associated with an increase in type 1 diabetes risk (inverse-variance weighted (IVW) MR odds ratio (OR) = 1.09, 95% CI: 0.86 to 1.40, p = 0.48). We obtained similar results using the 3 pleiotropy robust MR methods and in sensitivity analyses excluding SNPs associated with serum lipid levels, body composition, blood traits, and type 2 diabetes. Our findings indicate that decreased vitamin D levels did not have a substantial impact on risk of type 1 diabetes in the populations studied. Study limitations include an inability to exclude the existence of smaller associations and a lack of evidence from non-European populations.ConclusionsOur findings suggest that 25OHD levels are unlikely to have a large effect on risk of type 1 diabetes, but larger MR studies or RCTs are needed to investigate small effects.

Despoina Manousaki and co-workers investigate vitamin D levels and risk of type I diabetes.     

Low Vitamin D Status is Associated with Increased Thyrotropin-Receptor Antibody Titer in Graves Disease

ObjectiveVitamin D deficiency is reportedly linked to a variety of autoimmune diseases. However, the relationship between thyroid autoimmunity in Graves disease (GD) and vitamin D deficiency is unclear. The goal of this study was to determine whether increased thyroid hormone autoantibody titer is associated with vitamin D deficiency in GD patients.MethodsA total of 70 patients with GD and 70 matched control subjects were recruited to our study. The levels of 25-hydroxyvitamin D (25[OH]D), calcium, parathyroid hormone (PTH), free triiodothyronine (FT₃), free thyroxine (FT₄), thyroid-stimulating hormone (TSH), thyrotropin-receptor antibody (TRAb), thyroid-peroxidase antibody (TPOAb), and thyroglobulin antibody (TGAb) in serum collected from these patients and controls were examined.ResultsThe level of 25(OH)D in serum from TRAb-positive GD patients was significantly lower than that in serum of healthy controls or TRAb-negative patients. However, compared with control subjects, the level of PTH in serum was increased in TRAb-positive GD patients. The rate of vitamin D deficiency (defined as serum 25[OH]D < 50 nmol/L) in TRAb-positive GD patients was significantly higher than in healthy controls or TRAb-negative GD patients. The level of 25(OH)D in serum was inversely correlated with TRAb titer in serum of TRAb-positive GD patients. However, our results did not show a correlation between 25(OH)D level and the levels of TPOAb, TGAb, FT₃, FT₄, or TSH.ConclusionLow vitamin D status is associated with increased TRAb titer in GD, suggesting a possible link between vitamin D status and increased thyroid autoim-munity in GD patients. (Endocr Pract. 2015;21:258-263)     

Is Vitamin D the Fountain of Youth?

ObjectiveTo review the role of vitamin D deficiency for both classic and “nonclassic” effects and raise the caution that association does not prove causation.MethodsThe pertinent literature regarding vitamin D and its effects on bone, muscle function, immune function, glucose tolerance, cancer risk, and development of cardiovascular disease and other conditions is reviewed. In addition, the limitations of observational studies are discussed.ResultsVitamin D inadequacy is common worldwide and classically causes osteomalacia and rickets. More recently, the contribution of low vitamin D status to increased falls and fracture risk has become appreciated. Additionally, nonclassic effects of vitamin D inadequacy are being recognized, and low vitamin D status is being potentially associated with a multitude of conditions (including Alzheimer disease, osteoarthritis, multiple sclerosis, and hypertension) and higher overall mortality. It is important to recognize that associations in observational studies can be due to chance, bias, or confounders or may be indicative of causality.ConclusionBecause vitamin D deficiency has been established to have adverse musculoskeletal consequences, optimization of vitamin D status, for both the individual patient and the overall population, is indicated. (Endocr Pract. 2009;15:590-596)     

Vitamin D Deficiency at Melanoma Diagnosis Is Associated with Higher Breslow Thickness

BackgroundEpidemiological evidence shows that people with thicker, or higher stage, melanomas have lower vitamin D status compared to those with thinner tumours. Evidence from experimental studies is inconsistent, but some suggest that administration of vitamin D metabolites can decrease tumour aggressiveness.ObjectivesDetermine the relationship between vitamin D status at diagnosis and melanoma thickness (as an indicator of prognosis), in a subtropical setting with high melanoma incidence.MethodsWe recruited 100 melanoma patients in Brisbane, Australia within days of their diagnosis. Data on factors previously associated with melanoma risk or prognosis were collected by questionnaire and physical examination. Serum for 25-hydroxyvitamin D3 [25(OH)D] levels was collected prior to wider excision biopsy; histological indicators of prognosis were obtained from pathology reports. We used multivariable logistic regression models to analyse the association between Breslow thickness (≥0.75 mm compared to <0.75 mm), Clark level (2–5 compared to 1) and presence of mitoses, and vitamin D status.ResultsSerum 25(OH)D <50 nmol/L (versus ≥50 nmol/L) was associated with a nearly four-fold increase in risk of having a thicker tumour (Adjusted OR = 3.82, 95% CI: 1.03, 14.14; p = 0.04, adjusted for age, sex, skin phototype, body mass index and season at diagnosis). There was no significant association with Clark level or presence of mitosis. Serum 25(OH)D levels in the highest quartile (≥69.8 nmol/L) were not associated with a more favourable prognosis.ConclusionsVitamin D deficiency at the time of melanoma diagnosis is associated with thicker tumours that are likely to have a poorer prognosis. Ensuring vitamin D levels of 50 nmol/L or higher in this population could potentially result in 18% of melanomas having Breslow thickness of <0.75 mm rather than ≥0.75 mm.     

Vitamin D in athletes: focus on physical performance and musculoskeletal injuries

[Purpose]The aim of this review was to discuss the effects of vitamin D on physical performance and musculoskeletal injuries in athletes and provide information on the field applications of vitamin D. [Methods]A systematic review was conducted to identify studies on vitamin D in athletes that assessed serum vitamin D levels, vitamin D and physical performance, vitamin D and musculoskeletal injuries, and practical guidelines for supplementation of vitamin D. [Results]Several studies reported that a high proportion of athletes had vitamin D insufficiency or deficiency. Low serum levels of vitamin D in athletes were more pronounced in winter than in other seasons, and indoor athletes had lower serum vitamin D levels than outdoor athletes. Low vitamin D levels have been demonstrated to have negative effects on muscle strength, power, and endurance; increase stress fractures and other musculoskeletal injuries; and affect acute muscle injuries and inflammation following high-intensity exercises. Therefore, periodic assessment and monitoring of vitamin D levels are necessary in athletes; the recommended serum level of 25(OH)D is > 32 ng/mL and the preferred level is > 40 ng/mL (-1). In those with low levels of vitamin D, exposure to sunlight and an improved diet or supplements may be helpful. Particularly, 2000–6000 IU of supplemental vitamin D3 can be consumed daily. [Conclusion]Vitamin D is a potential nutritional factor that can significantly affect physical performance and musculoskeletal injuries in athletes. The importance and role of vitamin D in athletes should be emphasized, and the current levels of vitamin D should be assessed. Therefore, it is essential to periodically evaluate and monitor serum vitamin D levels in athletes.     

Vitamin D Deficiency and Insufficiency in Hospitalized COPD Patients

Introduction

31–77% of patients with COPD have vitamin D deficiency and insufficiency, with results being highly variable between studies. Vitamin D may also correlate with disease characteristics.

Aim

To find out the prevalence of vitamin D deficiency and insufficiency in patients with COPD admitted for exacerbation and a risk factors for lower vitamin D levels among comorbidities and COPD characteristics.

Methods

152 patients were studied for vitamin D serum levels (25(OH)D). All of them were also assessed for diabetes mellitus (DM) and metabolic syndrome (MS). Data were gathered also for smoking status and exacerbations in last year. All patients completed CAT and mMRC questionnaires and underwent spirometry.

Results

A total of 83,6% of patients have reduced levels of vitamin D. 42,8% (65/152) have vitamin D insufficiency (defined as 25–50 nmol/L) and 40,8% (62/152) have vitamin D deficiency (<25 nmol/L). The mean level of 25(OH)D for all patients is 31,97 nmol/L (95%CI 29,12–34,68). Vitamin D deficiency and insufficiency are more prevalent in females vs. males (97,7 vs 77,8%; p = 0.003). The prevalence and severity of vitamin D deficiency and insufficiency in this study is significantly higher when compared to an unselected Bulgarian population (prevalence 75,8%; mean level 38,75 nmol/L). Vitamin D levels correlate with quality of life (measured by the mMRC scale) and lung function (FVC, FEV1, FEV6, FEF2575, FEV3, but not with FEV1/FVC ratio and PEF), it does not correlate with the presence of arterial hypertension, DM, MS and number of moderate, severe and total exacerbations. Vitamin D deficiency is a risk factor for longer hospital stay.

Conclusions

The patients with COPD admitted for exacerbation are a risk group for vitamin D deficiency and insufficiency, which is associated with worse disease characteristics.     

Vitamin D,Calcium, and Cardiovascular Mortality: A Perspective from A Plenary Lecture Given at the Annual Meeting of the American Association of Clinical Endocrinologists

ObjectiveTo examine data showing associations between serum 25-hydroxyvitamin D levels and calcium intake and cardiovascular mortality.MethodsThe articles reviewed include those published from 1992-2011 derived from search engines (PubMed, Scopus, Medscape) using the following search terms: vitamin D, calcium, cardiovascular events, cardiovascular mortality, all-cause mortality, vascular calcification, chronic kidney disease, renal stones, and hypercalci- uria. Because these articles were not weighted (graded) on the level of evidence, this review reflects my own perspective on the data and how they should be applied to clinical management.ResultsFor skeletal health, vitamin D and calcium are both needed to ensure proper skeletal growth (modeling) and repair (remodeling). Nutritional deficiencies of either vitamin D or calcium may lead to a spectrum of metabolic bone disorders. Excessive consumption of either nutrient has been linked to a variety of medical disorders, such as hypercalcemia or renal stones. There have also been associations between vitamin D or calcium intake and cardiovascular disease. However, neither of these associations have established evidence nor known causality for increasing cardiovascular risk or all-cause mortality in patients with creatinine clearances greater than 60 mL/ min. In patients with more severe chronic kidney disease, stronger data link excess calcium (or phosphorus) intake and increase in vascular calcification, but not mortality. The safe upper limit for vitamin D intake is at least 4000 IU daily and probably 10 000 IU daily; for calcium, the safe upper limit is between 2000 and 3000 mg daily.ConclusionsWhile no solid scientific evidence validates that serum vitamin D levels between 15 and 70 ng/ mL are associated with increased cardiovascular disease risk, stronger but inconsistent evidence shows an association between calcium supplementation greater than 500 mg daily and an increase in cardiovascular disease risk. Most professional societies suggest that replacement levels of these nutrients be personalized with the goal of reaching a 25-hydroxyvitamin D concentration between 30 and 50 ng/ mL and a calcium intake of 1200 mg daily. (Endocr Pract. 2011;17:798-806)     

维生素D缺乏和2型糖尿病视网膜病变风险度的相关性研究

摘要 目的：是探讨维生素D缺乏与2型糖尿病（T2DM）患者视网膜病变（DR）发生风险度的关系。方法：选取2020年12月至2022年8月在新疆医科大学第二附属医院内分泌科住院的2型糖尿病患者作为研究对象。将209名患者根据眼底检查分为DR组（n=50）和正常眼底（NDR）组（n=159）。比较各组患者一般资料、实验室检查指标;采用Spearman分析法分析病程、FBG、HbAlC、25(OH)D与DR的相关性,采用Pearson分析居住地（城镇）、与维生素D缺乏、SBP与DR的相关性,采用Logistics回归分析DR发生的影响因素,比较各组患者维生素D缺乏、病程、FBG、HbA1c及25(OH)D对DR的预测价值。结果：DR组的居住地（农村）、FBG、HbA1c、病程等均大于NDR组,25(OH)D水平低于NDR组,DR组维生素D缺乏率大于NDR组,差异有统计学意义（P＜0.05）。Pearson相关性分析结果表明DR与居住地（城镇）呈负相关（P＜0.05）,与SBP、维生素D缺乏呈正相关（P＜0.05）;Spearman相关分析表明DR与25(OH)D呈负相关（P＜0.05）,与病程、空腹血糖和糖化血红蛋白等呈正相关（P＜0.05）。Logistic回归分析结果显示,维生素D缺乏、病程、FBG、HbA1c为DR的独立危险因素（P＜0.05）,维生素D缺乏的T2DM患者DR发病风险是维生素D不缺乏者的22.019倍（OR=22.019,95%CL 2.119~228.771,P＜0.05）。受试者工作特征（ROC）曲线分析显示,病程、FBG、HbA1c、25(OH)D作为联合变量可有效预测DR,ROC曲线下面积为0.924。结论：25(OH)D与DR呈负相关,维生素D缺乏可能与T2DM患者DR的发生有关。     

Race/Ethnicity-Specific Association of Vitamin D and Global DNA Methylation: Cross-Sectional and Interventional Findings

ObjectivesUnderstanding of the influence of vitamin D deficiency on epigenome will provide novel insights into the chronic disease risk. We tested our hypotheses that 1) vitamin D deficiency is associated with global hypomethylation and this association may be race/ethnicity dependent; and 2) vitamin D supplementation will increase global DNA methylation level.MethodsA two-stage design, cross-sectional observation followed by a 16 week randomized, double- blinded, placebo-controlled trial (RCT) of vitamin D3 supplementation, was undertaken. Global DNA methylation level (percentage of 5-methylcytosine, %5-mC) was quantified using leukocyte DNA with the MethylFlash^TM Methylated DNA Quantification kit (Epigentek). Global methylation data was obtained from 454 Caucasians and African Americans (42%) in the observation cohort and 58 African Americans with vitamin D deficiency in the dose responsive RCT.ResultsIn the cross-sectional study, African Americans had lower %5-mC than Caucasians (P = 0.04). A significant interaction was detected between plasma 25(OH)D and race on %5-mC (P = 0.05), as a positive association was observed between plasma 25(OH)D and %5-mC in African Americans (β = 0.20, p<0.01), but not in Caucasians (β = 0.03, p = 0.62). In the 16-week RCT, a dose-response benefit of vitamin D₃ supplementation was observed for %5-mC, as indicated by a significant linear upward trend (-0.01 ± 0.01%, placebo; 0.11 ± 0.01%, ~600 IU/day; 0.30 ± 0.01%, ~2,000 IU/day; and 0.65 ± 0.01%, ~4,000 IU/day group; P-trend = 0.04).ConclusionsVitamin D deficiency is associated with global hypomethylation in African Americans. Vitamin D3 supplementation increases global DNA methylation in a dose-response manner in African Americans with vitamin D deficiency.     

Primary Hyperparathyroidism and Vitamin D In African Americans

ObjectivesVitamin D deficiency is more common in African Americans than in the general population or other ethnicities. Vitamin D deficiency also occurs more frequently in patients with primary hyperparathyroidism (PHPT) than in the general population. Currently, the limited data on vitamin D deficiency in African Americans with primary hyperparathyroidism (PHPT) is inconsistent as to whether the vitamin D deficiency observed in PHPT is yet even more pronounced in Africans with PHPT relative to non-African Americans with PHPT.MethodsOn the basis of biochemical, radiological, and surgical (adenoma weight) parameters, African Americans have been reported to have a more severe form of PHPT than non-African Americans. However, comparative clinical manifestations of PHPT in African Americans have not been well described.ResultsCurrent guidelines recommend vitamin D repletion in mild, asymptomatic PHPT when levels of 25-hydroxyvitamin D are less than 20 ng/mL. Studies that reported vitamin D repletion with ergocalciferol or cholecalciferol in PHPT have not stratified data according to ethnicity. Discrepancies therefore exist between repleting vitamin D in African Americans who may potentially have a more severe PHPT profile, but simultaneously a more pronounced vitamin D deficiency.ConclusionEffectively designed clinical trials are necessary to evaluate the indications, efficacy, and safety of vitamin D in African Americans with PHPT. (Endocr Pract. 2012;18:947-953)     

Vitamin D in healthy Tunisian population: Preliminary results

BackgroundVitamin D deficiency is one of the most common medical conditions worldwide. In Tunisia, several studies evaluated Vitamin D status, but this was concerning specific populations (pregnant women, obese or diabetic patients and children with asthma). The only study that evaluated Vitamin D status in a healthy Tunisian population was conducted by Meddeb and associeties in 2002. The update of data available, based on the currently recommended limits, is necessary. This study aimed to estimate the prevalence of hypovitaminosis D in a healthy Tunisian population, and correlate the values with potential risk factors.MethodsIt was conducted on 209 Tunisian healthy subjects. Data collected included clinical characteristics and dietary intakes. We measured 25-hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH), glycemia, creatinine, calcium, phosphorus, and alkaline phosphatase concentrations. Hypovitaminosis D was retained for 25(OH)D concentrations <75 nmol/L. Vitamin D deficiency was defined by 25(OH)D concentrations <25 nmol/L.ResultsThe prevalence of hypovitaminosis D and vitamin D deficiency were respectively 92.3% and 47.6%. The main factors that were significantly associated with low vitamin D levels in our multivariate analysis were veiling, living in rural areas and sunscreen use. However, sex, age, socioeconomic level, phototype, solar exposure score, smoking and bone mass index, were not statistically associated with hypovitaminosis D. The study of relationship between vitamin D status and serum PTH levels showed a significative and negative correlation (P < 0.005).ConclusionsGiven the high prevalence of vitamin D, an adapted health policy is essential. A widespread vitamin D supplementation and food fortification seems to be necessary in Tunisia.     

Real-life use of vitamin D3-fortified bread and milk during a winter season: the effects of CYP2R1 and GC genes on 25-hydroxyvitamin D concentrations in Danish families,the VitmaD study

Common genetic variants rs10741657 and rs10766197 in CYP2R1 and rs4588 and rs842999 in GC and a combined genetic risk score (GRS) of these four variants influence late summer 25-hydroxyvitamin D (25(OH)D) concentrations. The objectives were to identify those who are most at risk of developing low vitamin D status during winter and to assess whether vitamin D₃-fortified bread and milk will increase 25(OH)D concentrations in those with genetically determined low 25(OH)D concentrations at late summer. We used data from the VitmaD study. Participants were allocated to either vitamin D₃-fortified bread and milk or non-fortified bread and milk during winter. In the fortification group, CYP2R1 (rs10741657) and GC (rs4588 and rs842999) were statistically significantly associated with winter 25(OH)D concentrations and CYP2R1 (rs10766197) was borderline significant. There was a negative linear trend between 25(OH)D concentrations and carriage of 0–8 risk alleles (p < 0.0001). No association was found for the control group (p = 0.1428). There was a significant positive linear relationship between different quintiles of total vitamin D intake and the increase in 25(OH)D concentrations among carriers of 0–2 (p = 0.0012), 3 (p = 0.0001), 4 (p = 0.0118) or 5 (p = 0.0029) risk alleles, but not among carriers of 6–8 risk alleles (p = 0.1051). Carriers of a high GRS were more prone to be vitamin D deficient compared to carriers of a low GRS. Furthermore, rs4588-AA carriers have a low but very stable 25(OH)D concentration, and interestingly, also low PTH level.

Electronic supplementary material

The online version of this article (doi:10.1007/s12263-014-0413-7) contains supplementary material, which is available to authorized users.     

Hypovitaminosis D and Bone Mineral Density in Human Immunodeficiency Virus-Infected Men from India,with or without Antiretroviral Therapy

ObjectiveTo study the vitamin D status and bone mineral density (BMD) in men infected with human immunodeficiency virus (HIV) in a tertiary care center from southern India.MethodsWe conducted a cross-sectional study of 35 HIV-infected men (between 20 and 50 years old) receiving highly active antiretroviral therapy (HAART) (group 1) in comparison with 35 ageand body mass index-matched HIV-positive antiretroviral therapy-naïve men (group 2) and 35 HIV-negative healthy control subjects (group 3).ResultsA significantly greater proportion (P = .002) of patients (74%) in the HAART group had vitamin D deficiency (< 20 ng/mL) in comparison with the other 2 groups (37% in each group). The mean intact parathyroid hormone level was higher (P < .001) and the mean duration of exposure to sunlight was lower (P = .001) in the HAART group than in the other 2 groups. By logistic regression analysis, HAART was found to be significantly associated with vitamin D deficiency. The BMD in the femoral neck was significantly lower in men with HIV infection who were receiving HAART in comparison with the other 2 groups (P = .006). On multivariate logistic regression, older age, low body mass index, and high parathyroid hormone levels emerged as factors significantly associated with decreased BMD at the femoral neck.ConclusionA significant proportion of patients receiving HAART had vitamin D deficiency. The secondary hyperparathyroidism probably due to vitamin D deficiency is an important contributing factor for the observed changes in BMD. Vitamin D deficiency noted in this group is probably multifactorial, and further research is needed to determine whether the effect of HAART on vitamin D metabolism is an additional causative factor and what benefit vitamin D supplementation might confer in these patients. (Endocr Pract. 2010;16:547-553)     

2型糖尿病合并肺部感染患者维生素D的表达及其临床意义

目的:研究2型糖尿病合并肺部感染患者维生素D的表达及其临床意义。方法:以2017年6月～2018年12月我院收治的2型糖尿病患者160例为研究对象。将所有患者按照是否发生肺部感染分为观察组(发生肺部感染)61例与对照组(未发生肺部感染)99例。分别比较两组患者基本资料、维生素D水平、血糖相关指标水平以及T淋巴细胞亚群相关指标,并分析2型糖尿病合并肺部感染患者维生素D与血糖指标、T淋巴细胞亚群相关指标的相关性。结果:两组患者年龄、性别以及糖尿病病程等基本资料对比差异均无统计学意义(均P0.05)。观察组患者空腹血糖、糖化血红蛋白水平高于对照组,而25(OH)D水平低于对照组,差异均有统计学意义(均P0.05)。观察组患者CD3~+、CD4~+以及CD4~+/CD8~+低于对照组,差异有统计学意义(均P0.05)。经Spearman相关性分析可得:25(OH)D与空腹血糖、糖化血红蛋白水平均呈负相关关系,而与CD3~+、CD4~+以及CD4~+/CD8~+均呈正相关关系(均P0.05)。结论:2型糖尿病合并肺部感染患者维生素D水平下降,通过检测维生素D水平,有助于评估患者的血糖水平与免疫功能状况。     

Tibial Tenderness Identifies Secondary Hyperparathyroidism Responding to High-Dose Vitamin D in Pakistani Women

ObjectiveTo assess the utility of anterior tibial tenderness (ATT) measured by visual analogue scoring (VAS) as a clinical diagnostic tool for vitamin D deficiency in a high-risk population of Pakistani women.MethodsATT was measured by VAS in 75 premenopausal women age 17 to 56 years (mean, 41.3 years) with generalized aches and pains and calcium <11 mg/dL (normal, 8 to 11 mg/dL) who were seen at a tertiary care center in Lahore, Pakistan. This was followed by administration of 1.8 million units of vitamin D3 in divided doses. ATT, vitamin D, and parathyroid hormone (PTH) levels were checked before and after the injections. Correlation between ATT, vitamin D, and PTH, as well as changes in ATT, vitamin D, and PTH following supplementation were determined.ResultsPre-intervention average calcium and vitamin D were 9.3 mg/dL (range, 8 to 10.3 mg/dL) and 12.1 ng/mL (range, 1.5 to 32.6 ng/mL), respectively. Seventy-four percent of the participants (53/75) had vitamin D deficiency and elevated PTH (>60 pg/mL). Mean PTH was 81.6 pg/mL (range, 29.1 to 370 pg/mL). Changes in ATT correlated strongly (r = 0.422; P = .013) with changes in PTH. Following supplementation, there was significant improvement in ATT (P<.01) and vitamin D level (P<.01), with a decrease in PTH level (P<.01).ConclusionATT is a valid clinical diagnostic measure of vitamin D deficiency in South Asian women. (Endocr Pract. 2013;19:596-601)     

1,25-Dihydroxyvitamin D3 Protects against Immune-Mediated Killing of Neurons in Culture and in Experimental Autoimmune Encephalomyelitis

Several studies have reported that low vitamin D levels are associated with an increased risk of developing multiple sclerosis (MS). As MS is an inflammatory disorder with degeneration of axons and neurons, we examined whether the biologically active form of vitamin D, 1,25-dihydroxyvitamin D₃ (1,25D₃), could protect against the T cell-mediated killing of human neurons in culture, and the axonal loss seen in mice with experimental autoimmune encephalomyelitis (EAE). Human neurons were exposed to activated human T lymphocytes and the loss of neurons was documented 24 hours later by counting the number of microtubule-associated protein-2 positive cells. Mice with EAE were harvested for counts of axonal profiles in the spinal cord. 1,25D₃ was exposed to T cells in culture or administered to mice from peak EAE clinical severity when axonal loss was already evolving. Activated T lymphocytes killed human neurons prominently within 24 hours but toxicity was significantly attenuated when T cells were exposed to 1,25D₃ prior to the co-culture. In EAE, 1,25D₃ treatment initiated from peak clinical severity reduced the extent of clinical disability and mitigated the progressive loss of axons. The reduction of axonal and neuronal loss by 1,25D₃ in the context of an inflammatory assault to the central nervous system is a potential contributor to the putative benefits of vitamin D in MS.