The predictive factors of low serum 25-hydroxyvitamin D and vitamin D deficiency in patients with systemic lupus erythematosus

Vitamin D is a steroid hormone with pleiotropic effects. The association between serum 25-hydroxyvitamin D level [25(OH) D] and lupus nephritis are not clearly known. We aim to determine serum 25(OH) D levels in patients with inactive SLE, active SLE without lupus nephritis (LN) and active SLE with LN and to identify clinical predictor of vitamin D deficiency. One hundred and eight SLE patients were included. Patients were classified as Group (Gr) 1, 2 and 3 if they had SLE disease activity index (SLEDAI) <3, ≥3 but no LN and ≥3 with LN. Important baseline characteristics were collected. 25(OH) D was measured by high performance liquid chromatography (HPLC). SLEDAI in Gr1, Gr2 and Gr3 was 0.7 (0.9), 5.6 (2.3) and 9.2 (5.2), respectively. 43.5 % had vitamin D insufficiency and 29.6 % had vitamin D deficiency. Mean 25(OH) D in each groups was 28.3 (8.0), 26.7 (9.5) and 19.9 (7.6) ng/ml (p < 0.001 comparing Gr1 and 3) (p = 0.003 comparing Gr2 and 3). Vitamin D deficiency was found in 11.1, 22.2 and 55.6 % of Gr1, 2 and 3. Linear regression analysis found that 25(OH) D was significantly correlated with serum albumin (r = 0.28, p = 0.004), inversely correlated with SLEDAI (r = ?0.22, p = 0.03) and urinary protein creatinine index (UPCI) (r = ?0.28, p = 0.005), but not with sun exposure score, body mass index and estimated GFR. Only UPCI was significantly inversely correlated with 25(OH) D (p = 0.02) from multiple linear regression. LN was a significant predictor of vitamin D deficiency from multivariate logistic regression (OR 5.97; p = 0.006). Vitamin D deficiency and insufficiency was found in 93 and 86 % of LN with proteinuria ≥ and <500 mg/day. We conclude that SLE patients with LN have significantly lower vitamin D level than inactive SLE and active SLE without LN. Hence, nephritis is a significant predictor of vitamin D deficiency in SLE patients.     

A randomized controlled trial of the effects of vitamin D on muscle strength and mobility in older women with vitamin D insufficiency

OBJECTIVES: To evaluate the effects of vitamin D treatment on muscle strength and mobility in older women with vitamin D insufficiency. DESIGN: One‐year population‐based, double‐blind, randomized, controlled trial. SETTING: Perth, Australia (latitude 32°S). PARTICIPANTS: Three hundred two community‐dwelling ambulant elderly women aged 70 to 90 with a serum 25‐hydroxyvitamin D (25(OH)D) concentration less than 24 ng/mL. INTERVENTION: Vitamin D₂ 1,000 IU/d or identical placebo; calcium citrate (1 g calcium/d) in both groups. MEASUREMENTS: Lower limb muscle strength and mobility as assessed using the Timed Up and Go Test (TUAG). RESULTS: At baseline, mean±standard deviation serum 25(OH)D was 17.7±4.2 ng/mL; this increased to 24.0±5.6 ng/mL in the vitamin D group after 1 year but remained the same in the placebo group. For hip extensor and adductor strength and TUAG, but not for other muscle groups, a significant interaction between treatment group and baseline values was noted. In those with baseline values in the lowest tertile, vitamin D improved muscle strength and TUAG more than calcium alone (mean (standard error): hip extensors 22.6% (9.5%); hip adductors 13.5% (6.7%), TUAG 17.5% (7.6%), P<.05). Baseline 25(OH)D levels did not influence patient response to supplementation. CONCLUSION: Vitamin D therapy was observed to increase muscle function in those who were the weakest and slowest at baseline. Vitamin D should be given to people with insufficiency or deficiency to improve muscle strength and mobility.     

Vitamin D deficiency and vitamin D therapy in chronic hepatitis C

Background. Vitamin D has immunomodulatory properties, exerts an anti-hepatitis C virus (HCV) effect in vitro and improves response to interferon-based therapy in patients with chronic hepatitis C (CHC). Low serum levels of 25(OH) vitamin D [25(OH)D] are frequently found in CHC patients and seem to be related to more advanced stages of liver fibrosis. The study aims to establish the incidence of vitamin D deficiency in Spanish patients with CHC, its possible relation with features of liver damage and with the IL28B gene polymorphism, and the immediate effect of vitamin D therapy on CHC-related analytical variables.Materials and methods. Baseline serum 25(OH)D levels were measured in 108 consecutive CHC patients (60 men, age 54.3 ± 10.5 yrs). Results of transient elastography and of IL28B rs12979860C/T genotype were available in 89 and 95 patients, respectively. Forty one patients with insufficient levels of 25(OH)D received vitamin D supplements and were re-evaluated thereafter.Results. Deficiency of vitamin D (< 20 µg/dL) and suboptimal levels (20–30 µg/mL) were detected in 36.1% and 40.9% of patients, respectively. No relationships were found between 25(OH)D levels and biochemical liver tests, fibrosis stage and IL28B genotype. Vitamin D therapy normalized 25(OH)D levels in all treated patients, but did not modify significantly HCV-RNA serum levels or biochemical tests.Conclusions. Vitamin D deficiency is common in Spanish patients with CHC but it is related neither to biochemical and virological variables nor with the fibrosis stage and IL28B polymorphism. Vitamin D therapy has no immediate effect on HCV-RNA serum levels.     

Effects of vitamin D supplementation on circulatory YKL-40 and MCP-1 biomarkers associated with vascular diabetic complications: A randomized,placebo-controlled,double-blind clinical trial

AimDiabetic patients predispose to vascular diseases such as nephropathy, and retinopathy. Poor adherence to medical treatment and dietary recommendations in uncontrolled diabetes leads to vascular damages. Vitamin D has been extensively studied and found to be protective against diabetes mellitus. YKL-40 and Monocyte chemoattractant protein-1 (MCP-1) are considered to exert crucial role in diabetes and its complications. Therefore, this study was designed to investigate effects of vitamin D supplementation on serum levels of YKL-40 and MCP-1 involved in the development of diabetic complications.MethodsFor 12 weeks, 48 type 2 diabetic patients enrolled in the trial and randomly were divided into two groups (n = 24 per group), receiving one of the following: 100 μg (4000 IU) vitamin D or placebo. Before and after intervention, serumYKL-40, MCP-1, insulin, IL-6, TNF-α, 25- (OH) vitamin D and HbA1c were measured.ResultsOur results revealed that serum levels of 25 (OH) vitamin D significantly increased in vitamin D group (p < 0.001). Vitamin D supplementation also significantly reduced serum YKL-40 levels (−22.7 vs. −2.4 ng/ml; (p-value = 0.003)). There was a significant decline in MCP-1 concentration in intervention group at the end of the study (−45.7 vs. −0.9 pg/ml; (p = 0.001)). Furthermore, there was a significant decrease in IL-6, fasting insulin and HOMA-IR in intervention group after 3 months supplementation.ConclusionsDaily vitamin D supplementation effectively reduced circulatory YKL-40 and MCP-1 levels in patients with type-2 diabetes and vitamin D deficiency. Vitamin D might contribute in reducing diabetic complications via modulating YKL-40 and MCP-1 signaling pathways.     

The impact of cholecalciferol on markers of vascular calcification in hemodialysis patients: A randomized placebo controlled study

Background and aimVascular calcification is an independent risk factor for cardiovascular diseases and all-cause mortality in end stage renal disease, and particularly in hemodialysis patients. Vitamin D deficiency has been shown to be associated with vascular calcification among this category of patients. Cholecalciferol or vitamin D3; the native inactivated 25-hydroxy vitamin D [25(OH)D], has been proposed to have a good impact on vascular calcification and vitamin D deficiency. However, clinical data is still limited.Methods and resultsA prospective, randomized, placebo-controlled study was carried out to evaluate the effect of oral cholecalciferol on vascular calcification and 25(OH)D levels in hemodialysis patients. A total of sixty eligible hemodialysis patients were randomly assigned to either a treatment group (Oral 200.000IU Cholecalciferol per month) or a placebo group, for 3 months. Serum 25-hydroxy vitamin D (25(OH)D), fetuin-A, fibroblast growth factor (FGF-23), osteoprotegerin (OPG), calcium, phosphorus, their product (CaXP) and intact parathyroid hormone (iPTH) levels, were all assessed at baseline and at the end of the study. ClinicalTrials.gov registration number: NCT03602430. Cholecalciferol significantly increased serum levels of 25(OH)D and fetuin-A in the treatment group (p-value < 0.001), while no significant difference was observed in the placebo group. Cholecalciferol administration showed no effect on either FGF-23 or OPG. None of the treatment group patients experienced any adverse effects.ConclusionCholecalciferol was shown to be an effective, tolerable, inexpensive pharmacotherapeutic option to overcome vitamin D deficiency, with a possible modulating effect on fetuin-A, among hemodialysis patients.ClinicalTrials.gov registration numberNCT03602430.     

Serum 25-hydroxyvitamin D levels are inversely associated with systemic inflammation in severe obese subjects

Obesity is frequently characterized by a reduced vitamin D bioavailability, as well as insulin-resistance and a chronic inflammatory response. We tested the hypothesis of an independent relationship between serum concentrations of 25-hydroxyvitamin D (25[OH]D) and several circulating inflammatory markers in a cohort of severely obese individuals. Cross-sectional study was carried out among obese patients undergoing a clinical evaluation before bariatric surgery in our University Hospital. Serum 25(OH)D, fasting and post load glucose and insulin, high-sensitive C-reactive protein (hs CRP), fibrinogen, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), leptin, adiponectin and lipid profile were collected. Insulin-resistance was assessed by insulin sensitivity index (ISI). Total body fat (FAT kg), total percent body fat (FAT%) and truncal fat mass (TrFAT) were assessed with dual-energy X-ray absorptiometry. A total of 147 obese subjects (89 women, 37.8 ± 7.1 years) with mean body mass index (BMI) of 43.6 ± 4.3 kg/m² were enrolled. Patients in the lowest tertile of 25(OH)D were significantly more obese with a higher amount of TrFAT, more insulin-resistant, and had higher levels of fasting and post-challenge glucose (p < 0.05 for all). In a multivariate regression analysis, serum 25(OH)D was inversely related to significant levels of hs CRP, IL-6 and TNF-α after accounting for age, gender, season of recruitment, BMI, FAT kg and TrFAT (p < 0.01 for all). In extremely obese subjects, 25(OH)D serum concentrations are inversely associated with several biomarkers of systemic inflammation, regardless of the total quantity of fat mass.     

Effect of cholecalciferol and calcium supplementation on muscle strength and energy metabolism in vitamin D‐deficient Asian Indians: a randomized,controlled trial

Context Vitamin D deficiency is prevalent worldwide. Vitamin D supplementation has shown variable effect on skeletal muscle strength in the elderly with hypovitaminosis D. There is a paucity of similar data in young individuals. Objective To study the effect of cholecalciferol and calcium supplementation on muscle strength and energy metabolism in young individuals. Subjects Forty healthy volunteers (24M/16F, mean age (SD) 31·5 ± 5·0 year) with hypovitaminosis D were randomized to either oral cholecalciferol (60 000 IU D3/week for 8 weeks followed by 60 000 IU/month for 4 months) with 1 g of elemental calcium daily or dual placebos for 6 months. Measurements Handgrip and gastro‐soleus dynamometry, pinch‐grip strength, respiratory pressures, 6‐min walk‐test and muscle energy metabolism on ³¹P magnetic resonance spectroscopy were assessed at baseline and after 6 months. Results The mean serum 25(OH)D in the supplemented and placebo groups at baseline, two and 6 months were 25·4 ± 9·9, 94·5 ± 53·8 and 56·0 ± 17·0 nm , and 21·1 ± 9·4, 32·8 ± 14·4 and 29·7 ± 15·0 nm , respectively. The supplemented group gained a handgrip strength of 2·4 kg (95% C.I. = 1·2–3·6); gastro‐soleus strength of 3·0 Nm (95% C.I. = 0·1–5·9) and walking distance of 15·9 m (95% C.I. = 6·3–25·5) over the placebo group after adjustment for age, gender and respective baseline parameters. Muscle energy parameters were comparable at 6 months. Conclusions Six months of cholecalciferol and calcium supplementation results in enhanced skeletal muscle strength and physical performance despite no change in muscle energy parameters. Cholecalciferol supplementation of 60 000 IU per month could not maintain 25(OH)D levels in the sufficient range.     

Vitamin D deficiency and the associated factors in children with type 1 diabetes mellitus in southern Iran

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disorder caused by destruction of beta cells of the pancreas. Several reports have suggested a connection between vitamin D deficiency and T1DM and the possible role of dietary vitamin D supplementation in reducing the risk of T1DM. There is little knowledge about the prevalence of vitamin D deficiency among Iranian children with T1DM. Serum 25-hydroxy vitamin D (25OHD) was assayed by high performance liquid chromatography in 8–18-year-old diabetic patients referred to pediatric diabetes clinics in Shiraz, Iran, during a period of 14 months. The age of the onset of T1DM, daily insulin usage, weight, height, and BMI of each patient were recorded along with levels of physical activity and sun exposure. The patients’ body composition was determined by DEXA and used in further analysis. This study was conducted on 39 diabetic boys and 46 diabetic girls aged 12.4 ± 4.2 years. Mean serum 25(OH)D3 was 18 ± 12.2 ng/dl. Serum levels of 25(OH)D3 were higher in boys than girls. 7.7 % of the boys and 30.4 % of the girls had severe vitamin D deficiency. There was a negative correlation between the age of the onset of T1DM and serum concentration of 25(OH)D3 (p = 0.006, r = ?0.17). Girls with T1DM showed a higher prevalence of severe vitamin D deficiency than boys with T1DM. Moreover, vitamin D deficiency was more prevalent in individuals with earlier onset of the disease and in those with higher fat mass index.     

Prevalence of and factors associated with vitamin D deficiency in 4,793 Japanese patients with rheumatoid arthritis

To determine the prevalence of vitamin D deficiency and associations with clinical characteristics in Japanese patients with rheumatoid arthritis (RA), serum 25(OH)D levels, laboratory data, and clinical data were obtained from 4,793 patients with RA (4,075 women, 718 men, mean age 59.7 years) who participated in the Institute of Rheumatology Rheumatoid Arthritis observational cohort study in April and May of 2011. Serum vitamin D levels were evaluated using a radioimmunoassay. We defined vitamin D deficiency as <20 ng/mL and severe deficiency as <10 ng/mL. Associations of vitamin D deficiency with patient characteristics were examined using multivariate logistic regression. Among all patients, the mean (SD) serum 25(OH)D level was 16.9 ng/mL (6.1), and the prevalence of vitamin D deficiency and severe deficiency were 71.8 and 11.5 %, respectively. In multivariate analysis, female gender, younger age, high Japanese version of health assessment questionnaire (HAQ) disability score, low serum total protein levels, low serum total cholesterol levels, high serum alkaline phosphate (ALP) levels, and non-steroidal anti-inflammatory drug (NSAID) use were significantly associated with vitamin D deficiency (P?<?0.01). Vitamin D deficiency appears to be common in Japanese patients with RA, as previously reported for patients of other ethnicities. Female gender, younger age, high HAQ disability score, low serum levels of total protein and total cholesterol, high serum ALP levels, and NSAID use appear to be associated with vitamin D deficiency in Japanese patients with RA.     

Frequency of vitamin D inadequacy among Saudi males visiting a Rheumatology Outpatient Clinic of a tertiary hospital in Al-Qassim region: Effect of vitamin D supplementation

Background: Vitamin D inadequacy (deficiency and insufficiency) has become an epidemic with the assumption that women in Arab countries are at a higher risk due to their clothing style of wearing dark colored suits or a veil. Aim of the work: To determine the frequency of vitamin D inadequacy among young adult and early middle-aged males in Al-Qassim region and to study the effect of vitamin D supplementation. Patients and methods: Sixty Saudi males visiting Rheumatology Outpatient Clinic of a tertiary hospital in Al-Qassim region were enrolled and evaluated for musculoskeletal state including assessment of chronic diffuse musculoskeletal pains using Numeric Rating Pain Scale (NRPS) and functional evaluation of lower limb proximal muscle power using chair–rise performance test. Serum 25(OH)D was evaluated. Vitamin D supplementation was provided for symptomatic subjects. Follow-up clinical evaluation as well as serum 25(OH)D measurement after 12 weeks vitamin D3 supplementation was performed. Results: The mean age of the patients was 43.2 ± 6.4 years. 54 (90%) had vitamin D inadequacy; 42 (70%) deficiency and 12 (20%) had insufficiency. Significant increase in baseline serum 25(OH)D (13.92 ± 5.67 ng/ml) after 12 weeks of supplementation (35.94 ± 4.11 ng/ml) with significant decrease in NPRS (7.42 ± 2.12 vs 2.06 ± 2.04) (p < 0.001), as well as significant improvement of functional status scores of chair–rise performance test (93.95 ± 23.56 vs 203.1 ± 58.6 (p < 0.001). Conclusion: Vitamin D inadequacy is a major health problem not only in elderly people or women with in-door residency and dark-colored clothes, but also in Saudi male young adults in Al-Qassim region.     

Effect of aromatase inhibition on serum levels of sclerostin and dickkopf-1, bone turnover markers and bone mineral density in women with breast cancer

Purpose

While their negative impact on bone health is well established, the effects of aromatase inhibition (AI) on Wnt inhibitors and osteoprotegerin (OPG) are unknown. The aim of the study was to investigate the effects of AI on serum levels of sclerostin, DKK-1 and OPG, as well as their associations with PINP and CTX as markers of bone turnover and bone mineral density (BMD) assessed by DXA.

Methods

We conducted a prospective longitudinal analysis of 70 postmenopausal women with hormone receptor-positive early breast cancer (BC) treated with anastrozole. All measurements were performed at baseline, 12 and 24 months of treatment. We measured the association of the investigated variables with circulating bone turnover markers, as well as with the BMD.

Results

After 24 months of AI therapy, sclerostin and OPG concentrations increased from 29.5 pmol/l (SD = 15.1) and 6.8 pmol/l (SD = 2.2) at baseline to 43.2 pmol/l (SD = 20.6) (p < 0.001) and 7.4 pmol/l (SD = 2.2) (p = 0.028), respectively. DKK-1 levels decreased from 34.3 pmol/l (SD = 13.5) at baseline to 29.7 pmol/l (SD = 12.3) at the 24-month visit (p = 0.005). Sclerostin levels significantly correlated with PTH, OPG and BMD of the lumbar spine, while DKK-1 correlated with the BMD of the femoral neck and of the total hip.

Conclusions

The observed increase in sclerostin levels indicates a central role of osteocytes in bone turnover in women with BC.     

Effects of Vitamin D Supplementation on Plasma Aldosterone and Renin—A Randomized Placebo‐Controlled Trial

Increasing evidence describes a possible interplay between vitamin D insufficiency with increased aldosterone. The authors sought to evaluate the effect of vitamin D supplementation on plasma aldosterone concentration (PAC) in patients with hypertension and 25‐hydroxyvitamin D[25(OH)D] insufficiency. The Styrian Vitamin D Hypertension Trial was a single‐center, double‐blind, placebo‐controlled randomized clinical trial conducted from 2011 to 2014. Two hundred patients with arterial hypertension and 25(OH)D levels <30 ng/mL were enrolled. Study participants were randomized to receive either 2800 IU of vitamin D3 or placebo. The present investigation is a post hoc analysis using analysis of covariance adjusting for baseline differences. A total of 188 participants (mean±standard deviation age, 60.1±11.3 years; 47% women; 25(OH)D, 21.2±5.6 ng/mL) completed the trial. Mean differences between baseline and follow‐up PAC in the control and intervention arm were +3.3 ng/dL and +0.9 ng/dL, respectively (P=.04). The findings indicate that vitamin D3 supplementation significantly decreases PAC in patients with arterial hypertension and 25(OH)D insufficiency.     

Relations of vitamin D status,gender and type 2 diabetes in middle-aged Caucasians

Vitamin D (Vit D) deficiency may be linked to the development of obesity-associated complications such as insulin resistance and type 2 diabetes. We therefore evaluated the relationship of Vit D serum concentrations with metabolic parameters and type 2 diabetes in middle-aged Caucasian men and women. One thousand six hundred and thirty-one Caucasians (832 males, 58.8 ± 9.7 years; 799 females, 59.7 ± 10.7 years) were evaluated in a cross-sectional study. Vit D status was assessed by measuring the serum concentration of 25-hydroxyvitamin D₃ [25(OH)D₃]. Type 2 diabetes prevalence was ascertained by medical history, fasting plasma glucose concentrations, oral glucose tolerance testing and/or glycosylated hemoglobin. Men displayed higher crude or seasonally adjusted 25(OH)D₃ serum concentrations than women (24.64 ± 10.98 vs. 22.88 ± 11.6 ng/ml; P < 0.001). Strong associations between body mass index (BMI) and 25(OH)D₃ were observed in both genders (P < 0.001). Seasonally adjusted levels of 25(OH)D₃ revealed stronger associations with type 2 diabetes in women than men (P < 0.001). However, adjustment for BMI and other confounding variables revealed an independent inverse association of 25(OH)D₃ with diabetes only in women (P < 0.001), whereas the association was abrogated in men. Using a 15 ng/ml 25(OH)D₃ cutoff for binary comparison, adjusted odds ratios for having newly diagnosed or known type 2 diabetes more than doubled (2.95 [95 % CI 1.37–4.89] and 3.26 [1.59–6.68], respectively), in women below the cutoff. We conclude that in women, but not in men, low 25(OH)D₃ serum levels are independently associated with type 2 diabetes. These findings suggest sex-specific effects of Vit D in the pathogenesis of type 2 diabetes.     

Effects of glucosamine sulfate and exercise therapy on serum leptin levels in patients with knee osteoarthritis: preliminary results of randomized controlled clinical trial

Osteoarthritis (OA) is a slow, chronic disease characterized by the focal deterioration and abrasion of articular cartilage. Leptin may play an important role in the pathophysiology of OA. Exercise and glucosamine sulfate therapy is one of the most commonly used in patients with knee OA. The goals of the present study are performed to investigate whether 12-week strength training program and glucosamine sulfate have an effect on serum leptin levels in knee OA and the relationship between leptin, clinical parameters, and radiographic severity of knee OA. Thirty-seven women with the diagnosis of knee OA were enrolled in the study. Patients were randomized into two groups. Group I (n = 19) received an exercise program, while group II (n = 18) received glucosamine sulfate (1,500 mg/day) in addition to the exercise therapy. Both groups were treated for 12 weeks. Leptin level was assessed at baseline and after 12 weeks. The concentration of leptin was measured by ELISA. The patients were evaluated regarding pain, disability, functional performance, and muscle strength. Both groups showed significant improvements in leptin levels, pain, disability, muscle strength, and functional performance with no statistically significant difference between the groups after the therapy. At basal time, plasma leptin levels were significantly correlated with body mass index and duration of disease, but no significant correlation was found with patient age, pain, disability, functional performance, muscle strength, and radiographic severity of knee OA. The results of this preliminary study revealed that exercise alone was adequate to prevent structural changes relieving the symptoms of OA. We also found that exercise alone could affect serum plasma levels of the leptin, important mediators of cartilage metabolism. Decreases in serum leptin may be one mechanism by which cartilage metabolism affects physical function and symptoms in OA patients.     

The effect of cholecalciferol supplementation on vitamin D levels and insulin sensitivity is dose related in vitamin D-deficient HIV-1-infected patients

Objective

The aim of this study was to explore the effects of cholecalciferol supplementation on vitamin D levels, bone mineral density (BMD), body fat distribution and insulin sensitivity in vitamin D‐deficient HIV‐1‐infected patients.

Methods

Twenty vitamin D‐deficient HIV‐1‐infected patients were prospectively treated with 2000 IU cholecalciferol/day for 14 weeks, whereafter treatment was continued with half this dosage until 48 weeks. BMD, body fat distribution, 1,25‐dihydroxy vitamin D₃ (1,25(OH)₂D₃), fasting glucose, insulin, adiponectin, leptin, interleukin (IL)‐6 and tumour necrosis factor (TNF)‐α were measured at baseline, and at 24 and 48 weeks. Parathyroid hormone (PTH), 25‐hydroxy vitamin D₃ [25(OH)D₃], cholesterol and triglycerides were measured at baseline, and at 12, 24 and 48 weeks.

Results

After 24 weeks, cholecalciferol supplementation significantly increased 25(OH)D₃ and 1,25(OH)₂D₃ levels and decreased PTH and insulin sensitivity. After 48 weeks, however, only 25(OH)D₃ levels remained significantly different from baseline, while the other parameter levels returned to baseline, suggesting a dose–response effect. Cholecalciferol had no effect on BMD, adipokines and triglycerides.

Conclusions

The effect of cholecalciferol treatment in this cohort appears to be dose dependent. Cholecalciferol dosages of ≥2000 IU are necessary to achieve 1,25(OH)₂D₃ levels that significantly decrease PTH, but also negatively affect insulin sensitivity. The results of this hypothesis‐driven explorative study need to be confirmed in larger clinical trials.     

Vitamin D in “early” primary Sjögren’s syndrome: does it play a role in influencing disease phenotypes?

Beyond its well-established role in the maintenance of mineral homeostasis, 25-OH-vitamin D deficiency seems to be involved in the development and severity of several autoimmune diseases. To date, contrasting data have been reported regarding the presence of hypovitaminosis D in primary Sjögren’s syndrome (pSS). To assess the prevalence of hypovitaminosis D in pSS at an early stage of the disease and to evaluate its impact on pSS clinical manifestations and disease activity, unselected consecutive subjects with recent onset dry mouth and/or dry eyes who underwent a comprehensive diagnostic algorithm for pSS (AECG criteria) were prospectively included in the study. The levels of 25[OH]-D3 were measured by monoclonal antibody immunoradiometric assay. Conditions of 25[OH]-D3 severe deficiency, deficiency, and insufficiency were defined as levels <10, <20, and 20–30 ng/ml, respectively, and their frequencies were investigated in pSS patients and controls. The levels of 25[OH]-D3 were also correlated with patients’ demographic, clinical, and serologic features. Seventy-six consecutive females were included: 30/76 patients fulfilled the AECG criteria for pSS. The remaining 46/76 patients represented the control group. No statistical differences were found in the serum levels of 25[OH]-D3 between pSS patients [median levels = 20 ng/ml (IQR 9.3–26)] and controls [median levels = 22.5 ng/ml (IQR 15.6–33)]. In particular, the frequency of 25[OH]-D3 severe deficiency was not significantly different in patients with pSS when compared to controls (23 vs. 17.4 %, p value = 0.24). We found a significant correlation between serum 25[OH]-D3 levels and white blood cells count (r = 0.29, p = 0.01). More specifically, leukocytopenia was significantly associated with 25[OH]-D3 severe deficiency, being documented in 40 % of the subjects with a 25[OH]-D3 severe deficiency and in 11 % of the subjects without a severe vitamin D deficiency (p = 0.02). We did not observe any further association or correlation between hypovitaminosis D and pSS glandular and extra-glandular features. Although the role of hypovitaminosis D in pSS pathogenesis remains controversial, the results of this study encourage the assessment of vitamin D in specific pSS subsets that could mostly benefit from a supplementation.     

Vitamin D Receptor (VDR) Gene Polymorphisms (<Emphasis Type="Italic">Fok</Emphasis>I, <Emphasis Type="Italic">Bsm</Emphasis>I) and their Relation to Vitamin D Status in Pediatrics βeta Thalassemia Major

Vitamin D is critical for calcium, phosphate homeostasis and for mineralization of the skeleton, especially during periods of rapid growth. Vitamin D Deficiency leads to rickets (in children) and osteomalacia (in adults). Expression and activation of the vitamin D receptor (VDR) are necessary for the effects of vitamin D, in which several single nucleotide polymorphisms have been identified especially (FokI, BsmI). In this study serum 25 (OH) vitamin D3 levels were estimated by Enzyme Linked Immunosorbent Assay [ELISA], VDR (FokI, BsmI) gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism assay [PCR–RFLP].Serum levels of calcium, phosphorus, alkaline phosphatase and ferritin were determined in 50 Pediatrics beta thalassemia major patients and 60 controls. Patients had significantly lower serum calcium (p < 0.001) lower serum vitamin D3 (p < 0.001) with elevated levels of phosphorus (p < 0.001) and alkaline phosphatase than controls (p = 0.04). Of the patients studied, 60 % had vitamin D deficiency (<20 ng/ml), 20 % had vitamin D insufficiency (21–30 ng/ml) and 20 % had sufficient vitamin D status (>30 ng/ml). Patients harboring mutant (Ff,ff) and wild (BB) genotypes were associated with lower serum calcium (p = 0.08, 0.02) respectively, lower vitamin D3 levels (p < 0.001, 0.01) respectively. They were also suffering from more bony complications although the difference was not statistically significant (p > 0.05). In conclusion, these results suggest that the VDR (FokI, BsmI) gene polymorphisms influence vitamin D status, (Ff,ff), BB genotypes had lower vitamin D levels, so they might influence risk of development of bone diseases in beta thalassemia major.     

Association of serum 25-hydroxyvitamin D and diabetes-related factors in Korean adults without diabetes: The Fifth Korea National Health and Nutrition Examination Survey 2010–2012

Aims

Vitamin D is associated with diabetes mellitus (DM) occurrence by affecting insulin secretion and resistance. However, variations exist due to differences in vitamin D sensitivity among individuals. We investigate the relationship between serum 25-hydroxyvitamin D [25(OH)D] status and various indices of DM in a Korean population without DM.

The effect of different doses of vitamin D3 on markers of vascular health in patients with type 2 diabetes: a randomised controlled trial

Aims/hypothesis

Low 25-hydroxyvitamin D levels predict future cardiovascular events and are common in patients with type 2 diabetes. We compared the effect of 100,000 and 200,000 IU doses of vitamin D₃ on endothelial function, blood pressure and markers of glycaemic control in patients with type 2 diabetes.

Methods

This was a randomised, parallel group, placebo-controlled trial. Patients with type 2 diabetes and baseline 25-hydroxyvitamin D levels <100 nmol/l were enrolled from community and hospital-based diabetes clinics. Participants were assessed in a university department of clinical pharmacology and received a single oral dose of placebo or vitamin D₃ (100,000 IU or 200,000 IU) at baseline, randomly allocated via numbered bottles prepared offsite; participants and investigators were both blinded to treatment allocation. Endothelial function, office blood pressure, B-type natriuretic peptide, insulin resistance and glycosylated haemoglobin were measured at baseline, and at 8 and 16 weeks.

Results

We randomised 61 participants to the three groups (placebo 22, 100,000 IU vitamin D₃ 19, 200,000 IU vitamin D₃ 20). There was no significant difference in the primary outcome of endothelial function at 8 weeks (placebo 5.2%, n?=?22; 100,000 IU 4.3%, n?=?19; 200,000 IU 4.9%, n?=?17) or at 16 weeks. Insulin resistance and glycosylated haemoglobin did not improve with either dose of vitamin D₃. On covariate analysis, systolic blood pressure was significantly lower in both treatment arms than in the placebo group at 8 weeks (placebo 146.4 mmHg, 100,000 IU 141.4 mmHg [p?=?0.04 vs placebo], 200,000 IU 136.8 mmHg [p?=?0.03 vs placebo]). B-type natriuretic peptide levels were significantly lower in the 200,000 IU group by 16 weeks (placebo 34 pg/ml, 200,000 IU 21 pg/ml, p?=?0.02). No significant excess of adverse effects was noted in the treatment arms.

Conclusions/interpretation

High-dose vitamin D₃ improved systolic blood pressure and B-type natriuretic peptide levels, but not endothelial function, insulin resistance or glycosylated haemoglobin in patients with type 2 diabetes.

Trial registration

ISRCTN50587697 (www.controlled-trials.com)

Funding

Diabetes UK, grant number 06/0003429. M. D. Witham is funded by a Scottish Government NES/CSO Clinician Scientist Award.     

25-Hydroxyvitamin D, cholesterol, and ultraviolet irradiation

Vitamin D deficiency may have implications for cardiovascular health. The purpose of this study was to determine the relationship of 25-hydroxyvitamin D (25[OH]D) to cholesterol and lipoprotein particles and to determine whether increasing 25(OH)D through ultraviolet (UV) irradiation impacted on these parameters in healthy young men and women. This was a randomized trial of 51 adults exposed to suberythemal doses of whole-body irradiation using UV lamps that emitted UV-A and UV-B radiation, compared with a control group, twice weekly for 12 weeks. 25-Hydroxyvitamin D, cholesterol, and lipoprotein subfractions were measured at baseline and after 12 weeks. There was a significant (P < .03) positive association between 25(OH)D and apolipoprotein A-I (Apo A-I) and lipoprotein A-I (Lp A-I). The ratio of low-density lipoprotein to high-density lipoprotein was significantly (P < or = .044) negatively correlated with 25(OH)D levels. The levels of 25(OH)D increased significantly in the treated compared with control group (P < .05). Overall, there were no significant differences between the treated and control groups in any lipoproteins or apolipoproteins after administration of UV irradiation. Subgroup analysis for Apo A-II confined to those with 25(OH)D insufficiency (25[OH]D <75 nmol/L [30 ng/mL]) revealed decreases in Apo A-II in the treated group and increases in the control group that were statistically significantly different between the groups (P = .026). We found a significant positive correlation between 25(OH)D and Apo A-I and Lp A-I and a significant negative correlation between 25(OH)D and the ratio of low-density lipoprotein to high-density lipoprotein. In those with vitamin D insufficiency, we found small decreases in Apo A-II in the treated relative to the control group. Overall, though, twice weekly exposure to UV radiation resulting in an increase in serum 25(OH)D had no significant impact on lipoprotein composition.