Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies)

OBJECTIVE: To determine whether treatment with low dose aspirin and heparin leads to a higher rate of live births than that achieved with low dose aspirin alone in women with a history of recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies), lupus anticoagulant, and cardiolipin antibodies (or anticardiolipin antibodies). DESIGN: Randomised controlled trial. SETTING: Specialist clinic for recurrent miscarriages. SUBJECTS: 90 women (median age 33 (range 22-43)) with a history of recurrent miscarriage (median number 4 (range 3-15)) and persistently positive results for phospholipid antibodies. INTERVENTION: Either low dose aspirin (75 mg daily) or low dose aspirin and 5000 U of unfractionated heparin subcutaneously 12 hourly. All women started treatment with low dose aspirin when they had a positive urine pregnancy test. Women were randomly allocated an intervention when fetal heart activity was seen on ultrasonography. Treatment was stopped at the time of miscarriage or at 34 weeks'' gestation. MAIN OUTCOME MEASURES: Rate of live births with the two treatments. RESULTS: There was no significant difference in the two groups in age or the number and gestation of previous miscarriages. The rate of live births with low dose aspirin and heparin was 71% (32/45 pregnancies) and 42% (19/45 pregnancies) with low dose aspirin alone (odds ratio 3.37 (95% confidence interval 1.40 to 8.10)). More than 90% of miscarriages occurred in the first trimester. There was no difference in outcome between the two treatments in pregnancies that advanced beyond 13 weeks'' gestation. Twelve of the 51 successful pregnancies (24%) were delivered before 37 weeks'' gestation. Women randomly allocated aspirin and heparin had a median decrease in lumbar spine bone density of 5.4% (range -8.6% to 1.7%). CONCLUSION: Treatment with aspirin and heparin leads to a significantly higher rate of live births in women with a history of recurrent miscarriage associated with phospholipid antibodies than that achieved with aspirin alone.     

Risk Factors for Vitamin D Deficiency among Veterans with and without HIV Infection

Objectives

We aimed to describe and compare the prevalence of vitamin D deficiency between HIV-negative and HIV-infected veterans in the southern United States, and to determine risk factors for vitamin D deficiency for HIV infected patients.

Methods

Cross-sectional, retrospective study including all patients followed at the Atlanta VA Medical Center with the first 25-hydroxyvitamin D [25(OH)D] level determined between January 2007 and August 2010. Multivariate logistic regression analysis was used to determine risk factors associated with vitamin D deficiency (< 20 ng/ml).

Results

There was higher prevalence of 25(OH)D deficiency among HIV-positive compared to HIV-negative patients (53.2 vs. 38.5%, p <0.001). Independent risk factors for vitamin D deficiency in HIV + patients included black race (OR 3.24, 95% CI 2.28–4.60), winter season (OR 1.39, 95% CI 1.05–1.84) and higher GFR (OR 1.01, CI 1.00–1.01); increasing age (OR 0.98, 95% CI 0.95–0.98), and tenofovir use (OR 0.72, 95% CI 0.54–0.96) were associated with less vitamin D deficiency.

Conclusions

Vitamin D deficiency is a prevalent problem that varies inversely with age and affects HIV-infected patients more than other veterans in care. In addition to age, tenofovir and kidney disease seem to confer a protective effect from vitamin D deficiency in HIV-positive patients.     

Common definition for categories of clinical research: a prerequisite for a survey on regulatory requirements by the European Clinical Research Infrastructures Network (ECRIN)

Background

Idiopathic recurrent miscarriage is defined as 3 consecutive pregnancy losses with no contributing features found on investigations. At present there are no treatments of proven efficacy for idiopathic recurrent miscarriage. Uterine natural killer (uNK) cells, the most predominant leucocyte in the endometrium are adjacent to foetal trophoblast cells and thought to be involved in implantation. The exact mechanisms of how uNK cells affect implantation are not clear but are probably through the regulation of angiogenesis. Multiple studies have shown an association between high density of uterine natural killer cells and recurrent miscarriage. We have shown that prednisolone reduces the number of uNK cells in the endometrium. The question remains as to whether reducing the number of uNK cells improves pregnancy outcome.

Methods

We propose a randomised, double-blind, placebo controlled trial of prednisolone with a pilot phase to assess feasibility of recruitment, integrity of trial procedures, and to generate data to base future power calculations. The primary aim is to investigate whether prednisolone therapy during the first trimester of pregnancy is able to improve live birth rates in patients with idiopathic recurrent miscarriage and raised uNK cells in the endometrium. Secondary outcomes include conception rate, karyotype of miscarriage, miscarriages (first and second trimester), stillbirths, pregnancy complications, gestational age at delivery, congenital abnormality and side effects of steroids. The trial has 2 stages: i) screening of non-pregnant women and ii) randomisation of the pregnant cohort. All patients who fit the inclusion criteria (<40 years old, ≥3 consecutive miscarriages with no cause found and no contraindications to prednisolone therapy) will be asked to consent to an endometrial biopsy in the mid-luteal phase to assess their levels of uNK cells. Women with high levels of uNK cells (≥5%), will be randomised to either prednisolone or placebo when a pregnancy is confirmed. Follow-up includes 2 weekly ultrasound scans in the first trimester, an anomaly scan at 20 weeks gestation, growth scans at 28 and 34 weeks gestation and a postnatal follow-up at 6 weeks.

Trial Registration

Current Controlled Trials ISRCTN28090716     

Correlates of 25-Hydroxyvitamin D among Chinese Breast Cancer Patients

Background

Few studies have investigated vitamin D status in association with modifiable lifestyle factors and clinical characteristics among breast cancer patients, with no studies among Chinese women, who may be at higher risk of vitamin D deficiency. We aimed to evaluate circulating 25-hydroxyvitamin D (25(OH)D) levels in association with clinical and lifestyle factors among 1,940 Chinese breast cancer patients.

Methods

Participants included breast cancer cases aged 22–77 from a population-based case-control study conducted in Shanghai, China during 1996–1998 (n = 1,044) and 2002–2005 (n = 896). Circulating 25(OH)D levels were measured in plasma samples (95% collected ≤6 months post-diagnosis). Prevalence ORs and 95% CIs were derived from multinomial logistic regression models, adjusting for age, season, and other factors.

Results

About 23% and 48% of women were vitamin D deficient (<30 nmol/L) or insufficient (30–50 nmol/L), respectively. Tumor characteristics were not associated with vitamin D status. Higher BMI was associated with increased odds of vitamin D deficiency (ORs (95% CIs): 1 (reference), 1.12 (0.85,1.47), and 1.57 (1.02,2.42), for <23, 23–<27.5, and ≥27.5 kg/m², respectively, P_trend <0.06). Total physical activity was associated with reduced odds of vitamin D deficiency (ORs (95% CIs):1 (reference), 0.84 (0.59,1.20), 0.65 (0.45,0.93), and 0.69 (0.48,1.00), for <7.65, 7.65–<10.6, 10.6–<13.5, ≥13.5 MET-hours/day, respectively, P_trend <0.02). Smoking was associated with vitamin D insufficiency and deficiency (ORs (95% CIs): 2.50 (1.07,5.84) and 2.78 (1.11,6.95), respectively).

Conclusions

In the largest study to date, the prevalence of low vitamin D status was high among Chinese breast cancer patients and associated with higher BMI, smoking, and lower physical activity. Our findings support careful monitoring of vitamin D status and recommendations for supplementation and other lifestyle modifications that may improve vitamin D status in breast cancer patients.     

Does suppressing luteinising hormone secretion reduce the miscarriage rate? Results of a randomised controlled trial.

OBJECTIVE--To determine whether prepregnancy pituitary suppression of luteinising hormone secretion with a luteinising hormone releasing hormone analogue improves the outcome of pregnancy in ovulatory women with a history of recurrent miscarriage, polycystic ovaries, and hypersecretion of luteinising hormone. DESIGN--Randomised controlled trial. SETTING--Specialist recurrent miscarriage clinic. SUBJECTS--106 women with a history of three or more consecutive first trimester miscarriages, polycystic ovaries, and hypersecretion of luteinising hormone. INTERVENTIONS--Women were randomised before conception to receive pituitary suppression with a luteinising hormone releasing hormone analogue followed by low dose ovulation induction and luteal phase progesterone (group 1) or were allowed to ovulate spontaneously and then given luteal phase progesterone alone or luteal phase placebo alone (group 2). No drugs were prescribed in pregnancy. MAIN OUTCOME MEASURES--Conception and live birth rates over six cycles. RESULTS--Conception rates in the pituitary suppression and luteal phase support groups were 80% (40/50 women) and 82% (46/56) respectively (NS). Live birth rates were 65% (26/40) and 76% (35/46) respectively (NS). In the luteal phase support group there was no difference in the outcome of pregnancy between women given progesterone and those given placebo pessaries. Live birth rates from an intention to treat analysis were 52% (26/50 pregnancies) in the group given pituitary suppression and 63% (35/56) in the controls (NS). CONCLUSIONS--Prepregnancy suppression of high luteinising hormone concentrations in ovulatory women with recurrent miscarriage and hypersecretion of luteinising hormone does not improve the outcome of pregnancy. The outcome of pregnancy without pituitary suppression is excellent.     

The Prevalence of Vitamin D Deficiency among Cancer Survivors in a Nationwide Survey of the Korean Population

Background

Recent studies have shown that inadequate vitamin D levels are associated with a poor cancer prognosis, but data regarding actual vitamin D levels in cancer survivors are limited. This study investigated the vitamin D levels and prevalence of vitamin D deficiency among Korean cancer survivors compared with non-cancer controls, and identified the factors associated with vitamin D deficiency.

Methods

Using the Korea National Health and Nutrition Examination Survey (KNHANES), 915 cancer survivors and 29,694 controls without a history of cancer were selected. Serum 25(OH)D levels were measured; vitamin D deficiency was defined as 25(OH)D levels less than 20 ng/mL. Chi-square tests and multiple logistic regression analyses were used to evaluate the prevalence of vitamin D deficiency and associated factors.

Results

Vitamin D deficiency was observed in 62.7% of cancer survivors and 67.1% of controls. Among cancer survivors, vitamin D deficiency was most prevalent among 19–44 year olds (76.2%) and among managers, professionals, and related workers (79.3%). Multiple logistic regression analysis revealed that younger cancer survivors and those who work indoors were predisposed to vitamin D deficiency.

Conclusion

Vitamin D deficiency was prevalent among both cancer survivors and controls in Korea. The regular evaluation and management of vitamin D levels is needed for both bone health and general health in cancer survivors.     

Insulin resistance and vitamin D deficiency in patients with chronic kidney disease stage 2-3

Vitamin D status and the relationship between serum 25(OH) vitamin D concentrations and the components of insulin resistance were examined in 120 patients with chronic kidney disease stage 2 and 3. Insulin sensitivity/resistance was calculated by the quantitative insulin sensitivity check index (QUICKI). In this analysis, the prevalence of insulin resistance was 42 %. Only 17 % of patients had serum 25(OH) vitamin D concentration in the recommended range (>/=30 ng/ml), 42 % suffered from vitamin D insufficiency and 41 % had moderate vitamin D deficiency. Insulin resistance significantly correlated with serum 25(OH)D and 1,25(OH)(2)D concentrations, renal function and protein excretion rate. Our results support the increasing evidence that vitamin D deficiency may be one of the factors participating in the development of insulin resistance already in the early stages of chronic kidney disease.     

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 Deficiency in Children with a Chronic Illness–Seasonal and Age-Related Variations in Serum 25-hydroxy Vitamin D Concentrations

Introduction

Children and adolescents with a chronic illness have potential risk factors for vitamin D deficiency. An optimal vitamin D status might have multiple health effects. This study evaluated vitamin D status and its association with age, gender, and season in a large cohort of chronically ill Finnish patients at a tertiary pediatric outpatient clinic. A cross-sectional register-based study was carried out, involving altogether 1351 children (51% boys, age range 0.2–18 years), who visited the outpatient clinic during 2007–2010 and had their vitamin D status (S-25-OHD) determined. A post-doc analysis was conducted to identify predisposing and preventing factors for vitamin D deficiency.

Results

Almost half (47%) of the S-25-OHD values were consistent with subnormal vitamin D status (S-25-OHD <50 nmol/L) while only 12% were >80 nmol/L. Age and season were the most important determinants for S-25-OHD concentration. Mean S-25-OHD concentration differed between age groups (Kruskal-Wallis; p<0.001), adolescents being at highest risk for vitamin D insufficiency. Young age and vitamin D supplementation were preventive factors for deficiency, while non-Finnish ethnic background was a predisposing factor. S-25-OHD showed significant seasonal variation in children older than 6 years. In the whole cohort, S-25-OHD was on average 13 nmol/L higher in summer than in winter, and the prevalence of vitamin D deficiency ( =  S-25-OHD <37.5 nmol/l) varied from 11% in summer to 29% in winter.

Conclusions

The finding that almost half of the studied Finnish children with a chronic illness had suboptimal vitamin D status is alarming. Inferior vitamin D status was noted in adolescents compared with younger children, suggesting that imbalance between intake and requirement evolves with age. Although less common during summer, subnormal vitamin D status was still observed in 28% of those evaluated in summer. Clinicians should identify individuals at risk and actively recommend vitamin D supplementation.     

Risk Factors for Vitamin D Deficiency among HIV-Infected and Uninfected Injection Drug Users

Introduction

Vitamin D deficiency is highly prevalent and is associated with bone disease, cardiovascular disease, metabolic syndrome and malignancy. Injection drug users (IDUs), with or without HIV infection, are at risk for these conditions; however, limited data on vitamin D deficiency exist in this population. We determined the prevalence and correlates of vitamin D deficiency among urban IDUs in the AIDS Linked to the IntraVenous Experience (ALIVE) Study cohort.

Methods

For this cross-sectional sub-study, vitamin D deficiency was defined as a serum 25(OH)-vitamin D level <20 ng/mL. Multivariable logistic regression was used to identify factors independently associated with vitamin D deficiency.

Results

Of 950 individuals analyzed, 29% were HIV-infected. The median age was 49 years; 65% were male, and 91% were black. The median vitamin D level was 13.5 ng/mL (IQR, 9.0–20.3); 74% were deficient (68% in HIV-infected vs. 76% in HIV-uninfected, p = 0.01). Non-black race, fall/winter season, multivitamin intake, higher serum albumin, HCV seropositivity and HIV-infection were associated with significantly lower odds of vitamin D deficiency.

Conclusions

Vitamin D deficiency is prevalent among IDUs. Notably, HIV-infected IDUs were less likely to be vitamin D deficient. Higher vitamin D levels were associated with multivitamin intake and with higher albumin levels, suggesting that nutritional status contributes substantially to deficiency. The association between HCV serostatus and vitamin D level remains unclear. Further investigation is needed to define the clinical implications of the heavy burden of vitamin D deficiency in this high-risk, aging population with significant co-morbidities.     

Severe vitamin D deficiency is associated with frequent exacerbations and hospitalization in COPD patients

Background

Acute exacerbations of COPD (AECOPD) are common and strongly influence disease severity and relative healthcare costs. Vitamin D deficiency is frequent among COPD patients and its contributory role in disease exacerbations is widely debated. Our aim was to assess the relationship of serum vitamin D levels with COPD severity and AECOPD.

Methods

Serum vitamin D (25-hydroxyvitamin D) levels were measured in 97 COPD patients and related to lung function, comorbidities, FEV1 decline, AECOPD and hospital admission during the previous year.

Results

Most patients (96%) had vitamin D deficiency, which was severe in 35 (36%). No significant relationship was found between vitamin D and FEV1 or annual FEV1 decline. No difference between patients with and without severe vitamin D deficiency was found in age, gender, BMI, smoking history, lung function, and comorbidities, apart from osteoporosis (60.9% in severe deficiency vs 22.7%, p = 0.001). In multiple logistic regression models, severe deficiency was independently associated with AECOPD [adjusted odds ratios (aOR) of 30.5 (95% CI 5.55, 168), p < 0.001] and hospitalization [aOR 3.83 (95% CI 1.29, 11.4), p = 0.02]. The odds ratio of being a frequent exacerbator if having severe vitamin D deficiency was 18.1 (95% CI 4.98, 65.8) (p < 0.001), while that of hospitalization was 4.57 (95% CI 1.83, 11.4) (p = 0.001).

Conclusions

In COPD patients severe vitamin D deficiency was related to more frequent disease exacerbations and hospitalization during the year previous to the measurement of vitamin D. This association was independent of patients’ characteristics and comorbidities.

Electronic supplementary material

The online version of this article (doi:10.1186/s12931-014-0131-0) contains supplementary material, which is available to authorized users.     

No correlation between pinopode formation and LIF and MMP2 expression in endometrium during implantation window

Implantation depends on two factors - embryo and endometrium. The period of maximal endometrial receptivity is a poorly understood phenomenon. We decided to look at three possible markers of implantation: pinopodes, leukemia inhibitory factor, and matrix metalloproteinase 2 and their correlations. We included in the study 23 idiopathic infertility patients and 21 patients with recurrent spontaneous abortions of unknown etiology. Twenty one fertile patients were also recruited. A biopsy was used for endometrial dating according to the Noyes and Hertig criteria, and assessed for the presence of pinopodes via a scanning electron microscope. Endometria were examined in Real Time-Polymerase Chain Reaction cycles for the mRNA expression of leukemia inhibitory factor (LIF) and matrix metalloproteinase 2 (MMP2). No difference was found in the stage of pinopodes development, nor in the coverage of endometrial surface between the studied groups. The expression level for LIF mRNA was lower in control patients compared to idiopathic infertility and recurrent miscarriage patients. No difference was detected in the expression of MMP2 between all studied groups. No correlation was found between pinopodes development stage and LIF and MMP2 expressions in endometrium. Of the studied factors, LIF and pinopodes show the most promise as potential markers of endometrial receptivity. However, the results achieved suggest that these markers are independent of each other.     

Vitamin D Deficiency—Prognostic Marker or Mortality Risk Factor in End Stage Renal Disease Patients with Diabetes Mellitus Treated with Hemodialysis—A Prospective Multicenter Study

BackgroundEnd stage renal disease (ESRD) patients on renal replacement therapy (RRT) with diabetes mellitus (DM) have a higher mortality rate and an increase prevalence of vitamin D deficiency compared to those without DM. It is still debated if vitamin D deficiency is a risk factor or a prognostic marker for mortality in these patients. This study investigated the prevalence of vitamin D deficiency and its impact on all-cause mortality in HD patients with DM.MethodsOur prospective non-interventional cohort study included 600 patients on hemodialysis therapy (HD) (median aged 56, interquartile range (19) years, 332 (55.3%) males) recruited from 7 HD centers, from all main geographical regions of Romania. The prevalence of DM was 15.3%. They were then followed regarding: dialysis duration, dialysis efficiency, renal anemia, CKD-MBD, inflammatory status and comorbidities: coronary artery disease (CAD), peripheral vascular disease (PVD) and stroke. The deficiency of 25-OH vitamin D was defined as a value lower than12 ng/mL.ResultsPatients were followed for 3 years. The overall 3 year mortality was 25.5% (153 individuals), being higher in patients with DM as compared to those without DM (33.7% vs. 24.0%; P = 0.049). The time-related prognosis was also influenced by the presence of DM, at the survival analysis resulting in a HR of 1.52 [1.03 to 2.26] 95% CI, P = 0.037, for death in dialyzed patients with DM. In DM patients, 25-OH vitamin D deficiency was significantly higher (37.0% compared to 24.0%, P = 0.009). Furthermore, in patients with DM we observed a shorter dialysis duration (2 vs. 3 years, P<0.001) and a lower intact parathyroid hormone (iPTH) (258.0 pg/ml vs. 441.9 pg/ml, P = 0.002). Regarding the presence of comorbidities at the inclusion in the study, the presence of diabetes in dialyzed patients was associated with increased prevalence of CAD (87.0% vs. 58.1%, P<0.001), PVD (67.4% vs. 17.3%, P<0.001) and history of stroke (29.3% vs. 14.0%, P<0.001). In patients with DM the presence of 25-OH vitamin D deficiency increased the probability of death (50.0% vs. 24.1%; P = 0.011). In multiple Cox proportional hazards analysis, vitamin D deficiency remained an independent predictor for mortality in dialysis patients with DM (HR = 1.71, 95% CI 1.21 to 2.43, P = 0.003). In the same time, multiple Cox proportional hazards analysis showed that age (HR = 1.02 per one year increase, P = 0.004), CAD (HR = 1.55, P = 0.046) and PVD (HR = 1.50, P = 0.029) were independent predictors for mortality in dialysis patients with DM.ConclusionsESRD patients with DM treated with HD have a higher overall mortality than non-DM patients. Vitamin D deficiency is significantly more prevalent in HD patients with DM. Low 25-OH vitamin D levels were associated with increased all-cause mortality in these patients. According to our data, in HD patients with DM, screening for vitamin D deficiency (and its correction) should be mandatory for an optimal risk reduction strategy.     

Recurrent aphthae: treatment with vitamin B12, folic acid,and iron.

A series of 130 consecutive outpatients with recurrent aphthous stomatitis were screened at the oral medicine department, Glasgow Dental Hospital, for deficienciesin vitamin b12, folic acid, and iron. In 23 patients (17.7%) such deficiencies werefound; five were deficient in vitamin B12, seven in folic acid, and 15 in iron. Four had more than one deficiency. Out of 130 controls matched for age and sex 11 (8.5%) were found to have deficiencies. The 23 deficient patients with recurrent aphthaewere treated with specific replacement therapy, and all 130 patients were followed up for at least one year. Of the 23 patients on replacement therapy 15 showed complete remission of ulceration and eight definite improvement. Of the 107 patientswith no deficiency receiving local symptomatic treatment only 33 had a remission or wereimproved. This difference was significant (P less than 0.001). Most patients withproved vitamin B12 or folic acid deficiency improved rapidly on replacement therapy;those with iron deficiency showed a less dramatic response. The 23 deficient patientswere further investigated to determine the cause of their deficiencies and detect the presence of any associated conditions. Four were found to have Addisonian perniciousanaemia. Seven had a malabsorption syndrome, which in five proved to be a gluten-induced enteropathy. In addition, there were single patients with idiopathic proctocolitis, diverticular disease of the colon, regional enterocolitis, and adenocarcinoma of thecaecum. We suggest that the high incidence of deficiencies found in this series andthe good response to replacement therapy shows the need for haematological screening of such patients.     

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。     

Effect of dietary calcium, phosphate and vitamin D deprivation on the pharmacokinetics of 1,25-dihydroxyvitamin D3 in the rat

The in vivo regulation of circulating 1,25(OH)2D3 concentrations by vitamin D status and by dietary calcium and phosphate deficiency was studied. Adult rats were cannulated in the jugular vein and the clearance of physiological doses of 1,25(OH)2D3 monitored. In vitamin D-replete rats we investigated the effects of dietary calcium and phosphate deficiency on the elimination half life of 1,25(OH)2D3 The results showed no effect of dietary phosphate deficiency on the elimination half life of 1,25(OH)2D3. Dietary calcium deficiency resulted in a small increase of the 1,25(OH)2D3 elimination half life (P = 0.04) (normal diet: 16.3 +/- 1.8 hrs, n = 6; -Ca diet: 18.6 +/- 1.1 hrs, n = 5; -P diet: 16.0 +/- 1.4 hrs, n = 6; mean +/- SD). The experiments with the vitamin D deficient rats showed a marked increase in the elimination half life of 1,25(OH)2D3 (36.4 +/- 6.8 hrs, n = 7), when compared to the rats on the normal diet (P = 0.001). From the experiments in the vitamin D replete rats one can infer that regulation of circulating 1,25(OH)2D3 concentrations by dietary calcium or phosphate takes place at the production site and not by changes in elimination rate. However, vitamin D status appears to regulate circulating 1,25(OH)2D3 concentrations also through an effect on the elimination rate.     

Colon cancer and solar ultraviolet B radiation and prevention and treatment of colon cancer in mice with vitamin D and its Gemini analogs

It has been recognized that people who live at higher latitudes and who are vitamin D deficient are at higher risk of dying from many common cancers including colon cancer. To evaluate the role of vitamin D deficiency on colon tumor growth, Balb/c adult male mice were fed either a vitamin D sufficient or vitamin D deficient diet for 10 weeks. Mice were arranged into groups of six and each animal received subcutaneously 10(4) MC-26 cells in the posterior trunk. The tumor size was recorded daily. By day 9 there was a significant difference in tumor volume between the vitamin D sufficient and vitamin D deficient mice. By day 18 the vitamin D deficient animals had a tumor size that was 56% larger compared to the animals that were vitamin D sufficient. To determine whether treatment with active vitamin D analogs could further decrease colon tumor growth in a vitamin D sufficient state, groups of mice were treated with the novel 19-nor-Gemini compounds. The mice were fed a low calcium diet. Twenty-four hours after tumor implantation, the mice received, three times weekly, one of the vitamin D analogs or the vehicle. The group that received Gemini 1,25-dihydroxy-21(3-hydroxy-3-trifluoromethyl-4-trifluoro-butynyl)-19-nor-20S-cholecalciferol (3) showed a dose-dependent decrease in tumor volume. On day 19, at the dose level of 0.02microg molar equivalents (E), the tumor volume was reduced by 41% when compared to the control group. At the same time point, the hexadeuterated analog 1,25-dihydroxy-21(3-hydroxy-3-trifluoromethyl-4-trifluoro-butynyl)-26,27-hexadeutero-19-nor-20S-cholecalciferol (4), administered at the 10-fold lower dose of 0.002microgE, showed a 52% reduction in tumor volume (p<0.05), compared to the control group. Animals that received 1,25(OH)(2)D(3) at 0.002 and 0.02microg showed a trend in tumor volume reduction at the highest dose but the changes were not statistically significant. An evaluation of serum calcium concentrations revealed that the calcium levels were normal in all groups, except the group receiving 0.02microgE of 4. The results from these studies demonstrate that vitamin D deficiency may accelerate colon cancer growth and that novel Gemini analogs of 1,25(OH)(2)D(3) may be an effective new approach for colon cancer treatment.     

Hashimoto Thyroiditis not Associated with Vitamin D Deficiency

Objective: Vitamin D deficiency is associated with several autoimmune diseases. This study assessed whether vitamin D deficiency is associated with Hashimoto thyroiditis (HT).Methods: Two groups of patients were selected for which serum 25-hydroxyvitamin D (25(OH)D) levels had been measured: (1) a study group of patients diagnosed with HT as indicated by thyroid antibodies, and (2) a healthy control group. Each group was separated by sex and then controlled for age and body mass index (BMI). Groups' mean 25(OH)D levels were compared by analysis of variance (ANOVA), and percent frequencies of vitamin D sufficiency, insufficiency, and deficiency were compared with a Z-test. The correlations between 25(OH)D levels and thyroid antibodies and thyroid-stimulating hormone (TSH) levels were also tested.Results: The mean 25(OH)D levels for the HT and control groups were significantly different in females (30.75 vs. 27.56 ng/mL, respectively) but not in males (14.24 vs. 13.26 ng/mL). HT females had a higher rate of vitamin D sufficiency (51.7% vs. 31.1%) and a lower rate of insufficiency (48.3% vs. 68.9%) relative to control females. No such differences were found in the male groups. None of the females were vitamin D deficient, but almost all males were. A significant (P = .016) positive correlation (r_s = 0.436) between 25(OH)D and TPOAb was observed in males.Conclusion: HT is not associated with higher rates of vitamin D deficiency relative to a control group.Abbreviations:BMI = body mass indexHT = Hashimoto thyroiditis25(OH)D = 25-hydroxyvitamin DTgAb = thyroglobulin antibodyTSH = thyroid-stimulating hormoneTPOAb = thyroid-peroxidase antibodyVDR = Vitamin D receptor     

Prevalence of Vitamin D Deficiency in Singapore: Its Implications to Cardiovascular Risk Factors

Objective

Vitamin D deficiency is a global health challenge and has been linked to type 2 diabetes and other chronic diseases. However, the relationship between vitamin D status, body composition, and cardiovascular risks has not been well characterized in Asian populations. The objectives of this study were to examine the factors associated with the low vitamin D levels in a sunny tropical region and to assess the role of vitamin D status in cardiovascular risk factors.

Design and Methods

This was a cross-sectional study. One hundred and fourteen healthy participants (59 males and 55 females) residing in Singapore took part in this study. Plasma 25OH-D₃ concentration was measured by using LC-MS/MS. Body fat (%) was measured by using three different techniques including bioelectrical impedance analysis (BIA), BOD POD, and dual-energy X-ray absorptiometry (DEXA). Basic anthropometric measurements, fasting blood glucose (FBG), fasting serum insulin (FSI), and lipid profiles were obtained using standard protocols.

Results

Approximately 42% of the participants were vitamin D deficient (< 20 ng/mL). Vitamin D status was inversely associated with body fat (%), homeostasis model assessment of insulin resistance (HOMA-IR), and total cholesterol/high density lipoprotein (TC/HDL) ratio, while positively associated with lean body mass (LBM) and hand grip strength (HGS).

Conclusions

The high prevalence of vitamin D deficiency in a sunny tropical region reinforces the need to recognize that sunlight alone is not the precursor for optimal vitamin D status. This raises the need to investigate public health measures that will encourage exposure to sunlight without overexposure that is harmful to skin. More importantly, vitamin D deficiency is associated with increased cardiovascular risks, i.e. HOMA-IR, TC/HDL, and LDL/HDL. Future studies should attempt to elucidate the potential mechanisms.     

Correlation of Symptoms with Vitamin D Deficiency and Symptom Response to Cholecalciferol Treatment: a Randomized Controlled Trial

ObjectiveTo examine the association of symptoms with vitamin D deficiency and symptom response to cholecalciferol treatment in a randomized, double-blind, placebo-controlled trial.MethodsAdult primary care patients in Duluth, Minnesota, were screened for vitamin D deficiency in February 2007. Participants completed questionnaires pertaining to a variety of symptoms, vitamin D intake, and selected medical conditions. Patients with mild to moderate vitamin D deficiency (25-hydroxyvitamin D [25(OH)D], 10-25 ng/mL) participated in a randomized controlled trial (RCT) of vitamin D replacement and its effect on symptoms. Participants were randomly assigned to receive 50000 units of cholecalciferol (vitamin D₃) weekly or placebo for 8 weeks. Patients with severe vitamin D deficiency (25[OH]D < 10 ng/mL) were treated in an unblinded fashion, and symptoms were reevaluated post treatment.ResultsA total of 610 patients underwent initial screening, and 100 patients with mild to moderate vitamin D deficiency participated in the RCT. Thirty-eight severely deficient patients were treated in an unblinded fashion. On initial screening, 46.2% of participants were deficient in vitamin D. Self-reported vitamin D supplementation, milk intake, celiac disease, gastric bypass, and chronic pancreatitis were predictive of vitamin D status. Severely deficient participants reported increased musculoskeletal symptoms, depression (including seasonal), and higher (worse) scores on a fibromyalgia assessment questionnaire. In the RCT, the treated group showed significant improvement in fibromyalgia assessment scores (P = 0.03), whereas the placebo-treated participants did not. Severely deficient patients did not show symptom improvement over the 8-week trial period or when followed up 1 year later.ConclusionsCompared with participants in the placebo group, patients in the treatment group showed mild short-term improvement in the overall fibromyalgia impact score, but did not show significant improvement in most musculoskeletal symptoms or in activities of daily living. (Endocr Pract. 2009;15:203-212)