维生素D缺乏与慢性阻塞性肺疾病

维生素D除了调节钙磷代谢外,近年来大量证据表明它还通过调节炎症因子、氧化应激,以及气道重塑等影响COPD的发展过程。此外,维生素D还能加强呼吸道上皮抗菌肽的表达而产生重要的先天免疫,能够减少病原体负荷和阻塞性肺疾病急性加重的频度。COPD患者的维生素D缺乏经常发生,而且与疾病严重程度相关,因此,严重的COPD患者应该补充维生素D。     

Vitamin D deficiency, vitamin D receptor gene polymorphisms and cardiovascular risk factors in Caribbean patients with type 2 diabetes

Aim

The prevalence of diabetes in the French West Indies is three times higher than in mainland France. We aimed to assess the associations between vitamin D deficiency, vitamin D receptor (VDR) gene polymorphisms and cardiovascular risk factors in Caribbean patients with type 2 diabetes (T2D).

Methods

In this cross-sectional study of 277 patients, 25-hydroxyvitamin D was measured by radioimmunoassay. FokI, BsmI, ApaI and TaqI single nucleotide polymorphisms (SNPs) of the VDR gene were genotyped. Analysis of covariance and logistic regression were performed.

Results

The study included 76 patients of Indian descent and 201 patients of African descent. The prevalence of vitamin D deficiency (< 20 ng/mL) was 42.6%. When patients were classified into groups with (G1) and without (G2) vitamin D deficiency, there were no significant differences in age, systolic blood pressure, low-density lipoprotein cholesterol and HbA_1c, although body mass index was significantly higher in G1. Vitamin D deficiency was significantly associated with increased diastolic blood pressure and triglyceride levels, and reduced high-density lipoprotein cholesterol (P < 0.05). Prevalence of vitamin D deficiency was decreased in patients carrying the f allele of FokI (OR: 0.52; P = 0.02) and the aa genotype of ApaI (OR: 0.46; P = 0.05). BsmI and TaqI SNPs were not associated with vitamin D deficiency.

Conclusion

The rate of vitamin D deficiency was high in our T2D patients, and was associated with the VDR gene FokI and ApaI polymorphisms and cardiovascular risk profile. Measurements of vitamin D may help to detect T2D patients with cardiovascular risk, and VDR polymorphisms might explain why vitamin D deficiency is so frequently seen in some T2D patients.     

Potential pathophysiological role for the vitamin D deficiency in essential hypertension

Vitamin D deficiency has been indicated as a pandemicemerging public health problem. In addition to the well-known role on calcium-phosphorus homeostasis in thebone, vitamin D-mediated processes have been recentlyinvestigated on other diseases, such as infections, can-cer and cardiovascular diseases. Recently, both the dis-covery of paracrine actions of vitamin D(recognized aslocal vitamin D system) and the link of vitamin D with renin-angiotensin-aldosterone system and the fibroblast growth factor 23/klotho pathways highlighted its ac-tive cardiovascular activity. Focusing on hypertension, this review summarizes the more recent experimental evidence involving the vitamin D system and deficiency in the cardiovascular pathophysiology. In particular, we updated the vascular synthesis/catabolism of vitamin D and its complex interactions between the various endocrine networks involved in the regulation of blood pressure in humans. On the other hand, the conflicting results emerged from the comparison between obser-vational and interventional studies emphasize the frag-mentary nature of our knowledge in the field of vitamin D and hypertension, strongly suggesting the need of further researches in this field.     

The vitamin D system: a crosstalk between the heart and kidney

Chronic kidney disease (CKD) independently increases the rates of cardiovascular disease, whereas the severity of kidney disease correlates with increased cardiovascular morbidity and death. Vitamin D is modified in the liver and the kidney to its active form (1,25‐dihydroxyvitamin D) by the 25‐hydroxy vitamin D 1‐hydroxylase enzyme (CYP27B1). The activated vitamin D brings about its actions through the vitamin D receptor (VDR). The VDRs and CYP27B1 have recently been shown to be expressed in several tissues, not directly involved in mineral homeostasis, including the cardiovascular, immune, and epithelial systems. The action of vitamin D in these tissues is implicated in the regulation of endothelial, vascular smooth muscle, and cardiac cell function, the renin–angiotensin system, inflammatory and fibrotic pathways, and immune response. Impaired VDR activation and signalling results in cellular dysfunction in several organs and biological systems, which leads to reduced bone health, an increased risk for epithelial cancers, metabolic disease, and uncontrolled inflammatory responses. Failure of cardiovascular VDR activation results in hypertension, accelerated atherosclerosis and vascular calcification, cardiac hypertrophy with vascular rarification and fibrosis, and progressive renal dysfunction. An emerging body of evidence has prompted attention to the relationship between CKD, mineral bone disorder (CKD‐MBD), and cardiovascular disease in the new guidelines from Kidney Disease: Improving Global Outcomes. Vitamin D receptor activators, commonly used to treat CKD‐MBD, and an appropriate treatment of vitamin D hormonal system failure in patients with CKD, may help to reduce cardiovascular morbidity and mortality in these patients.     

Serum vitamin D and colonic vitamin D receptor in inflammatory bowel disease

AIM: To determine serum vitamin D levels and colonic vitamin D receptor(VDR) expression in inflammatory bowel disease(IBD) and non-IBD patients and correlate these with histopathology.METHODS: Puerto Rican IBD(n = 10) and non-IBD(n = 10) patients ≥ 21 years old scheduled for colonoscopy were recruited. Each patient completed a questionnaire and provided a serum sample and a colonic biopsy of normal-appearing mucosa. For IBD patients, an additional biopsy was collected from visually diseased mucosa. Serum vitamin D levels were measured by ultra-performance liquid chromatography and mass spectrometry. Hematoxylin and eosin stained tissue sections from colonic biopsies were classified histologically as normal or colitis(active/inactive), and scored for the degree of inflammation present(0-3, inactive/absent to severe). Tissue sections from colonic biopsies were also stained by immunohistochemistry for VDR, for which representative diagnostic areas were photographed and scored for staining intensity using a 4-point scale.RESULTS: The IBD cohort was significantly younger(40.40 ± 5.27, P 0.05) than the non-IBD cohort(56.70 ± 1.64) with a higher prevalence of vitamin D deficiency(40% vs 20%, respectively) and insufficiency(70% vs 50%, respectively). Histologic inflammation was significantly higher in visually diseased mucosa from IBD patients(1.95 ± 0.25) than in normalappearing mucosa from control patients(0.25 ± 0.08, P 0.01) and from IBD patients(0.65 ± 0.36, P 0.05) and correlated inversely with VDR expression in visually diseased colonic tissue from IBD patients(r =-0.44, P 0.05) and from IBD patients with Crohn's disease(r =-0.69, P 0.05), but not in normal-appearing colonic tissue from control patients or IBD patients. Control and IBD patient serum vitamin D levels correlated positively with VDR expression in normal colon from control and IBD patients(r = 0.38, P 0.05) and with patient age(r = 0.54, P 0.01). CONCLUSION: Levels of serum vitamin D correlate positively with colonic VDR expression in visually normal mucosa whereas inflammation correlates negatively with colonic VDR expression in visually diseased mucosa in Puerto Rican patients.     

季节变化与心血管病人死亡关系调查

目的:调查我科住院心血管病人死亡与季节的关系。方法:查阅1993年1月～2004年12月12年来在我科住院死亡的269例病人资料,调查主要的5个病种死亡的季节规律性。结果:(1)季节性:心血管病人冬季死亡率最高,占36.8%(99/269,P<0.01),其他依次为春、秋、夏季;(2)冬季死亡病种:冠心病(CHD)死亡率最高,为79例,占79.8%(P<0.01),其他依次为高血压,主动脉夹层;(3)冠心病:174例CHD死亡患者中,冬季死亡率最高,为79例,占45.4%(P<0.01),其他依次是秋、春、夏季;(4)高血压:在41例高血压死亡病例中,20例死于春季,占48.8%,死亡率最高(P<0.01),其他依次是冬、秋、夏季;(5)其他:风心病15例,心肌病13例死亡病例中均以夏季死亡率最高,分别占46.7%,53.8%(P<0.01),其他依次为秋、冬、春季。结论:心血管病人的死亡率与季节变化相关,要根据其规律性,做好防治工作,降低死亡率。     

Role of vitamin D in the pathogenesis of atheromatosis

Background and aimsCardiovascular disease is the main cause of death worldwide, but the collective efforts to prevent this pathological condition are directed exclusively to individuals at higher risk due to hypercholesterolemia, hypertension, obesity, diabetes. Recently, vitamin D deficiency was identified as a risk factor for cardiovascular disease in healthy people, as it predisposes to different vascular dysfunctions that can result in plaque development and fragility. In this scenario, the fundamental aim of the study was to reproduce a disease model inducing vitamin D deficiency and atheromatosis in ApoE^?/- mice and then to evaluate the impact of this vitamin D status on the onset/progression of atheromatosis, focusing on plaque formation and instability.Methods and resultsIn our murine disease model, vitamin D deficiency was achieved by 3 weeks of vitamin D deficient diet along with intraperitoneal paricalcitol injections, while atheromatosis by western-type diet administration. Under these experimental conditions, vitamin D deficient mice developed more unstable atheromatous plaques with reduced or absent fibrotic cap. Since calcium and phosphorus metabolism and also cholesterol and triglycerides systemic concentration were not affected by vitamin D level, our results highlighted the role of vitamin D deficiency in the formation/instability of atheromatous plaque and, although further studies are needed, suggested a possible intervention with vitamin D to prevent or delay the atheromatous disease.ConclusionsThe data obtained open the question about the potential role of the vitamins in the pharmacological treatments of cardiovascular disorders as coadjutant of the primary drugs used for these pathologies.     

Interplay of vitamin D and metabolic syndrome: A review

Vitamin D deficiency is a worldwide public health problem. Vitamin D deficiency plays key role in the pathophysiology of risk factors of metabolic syndrome which affect cardiovascular system, increase insulin resistance and obesity, stimulate rennin–angiotensin–aldosterone system that cause hypertension. The discovery of vitamin D receptor expressed ubiquitously in almost all body cells such as immune, vascular and myocardial cells, pancreatic beta cells, neurons and osteoblasts suggests an involvement of vitamin D mediated effects on metabolic syndrome. Moreover vitamin D deficiency as well as cardiovascular diseases and related risk factors frequently co-occur. This underlines the importance of understanding the role of vitamin D in the context of metabolic syndrome. The paper provides an insight into the physiology of vitamin D and relationship of vitamin D deficiency with risk factors of metabolic syndrome through observational and supplementation studies.     

Vitamin D deficiency amongst minority ethnic groups in the UK: a cross sectional study

Background

Vitamin D deficiency is common amongst minority groups in Britain but its magnitude amongst South Asian (SA) and Black African-Caribbean (AC) groups is not well defined. The steroidal, endocrine nature of vitamin D provides it with a putative link with cardiovascular disease (CVD), and we hypothesised that aberrant levels of this hormone would reflect a heightened risk of CVD in these ethnic groups.

Methods

SA (n = 1105, 57% male) and AC (n = 748, 51% male) were recruited as part of a community heart failure study from 20 primary care practices, Birmingham, UK. Vitamin D₂/D₃ levels were measured to determine rates of total vitamin D status, which were age/sex adjusted.

Results

The majority of SAs had severe vitamin D deficiency (42.2%, 95% CI: 39.2–45.1), which was more frequent than in AC (12.5%, 10.2–14.9, p < 0.001. Vitamin status in SA and AC was unrelated to the presence of osteoporosis, and on multivariate analysis of SA, vitamin D levels were independently associated with age (β = 0.18, p < 0.001), haemoglobin (β = 0.12, p = 0.002), and negatively with alkaline phosphatase (a marker of bone mineralisation, β = − 0.11, p = 0.022). Amongst AC, vitamin D was independently associated with having ever smoked (β = − 0.13, p = 0.006) and systolic blood pressure (β = 0.10, p = 0.038).

Conclusions

Vitamin D deficiency is a frequent biochemical observation amongst minority groups in Britain but the clinical significance is unclear, and ethnically specific. A proportionate susceptibility to bone disease is not apparent in either minority group.     

The role of vitamin D deficiency in sepsis and potential therapeutic implications

Recent studies have shown that vitamin D has important functions besides bone and calcium homeostasis. Cells of the innate and adaptive immune system express vitamin D receptors and respond to stimulation by 1, 25-dihydroxyvitamin D. Patients with sepsis have a high mortality rate as well as a high prevalence of vitamin D deficiency. In addition, septic patients have decreased vitamin D binding protein levels which further exacerbates vitamin D deficiency. Therapy with vitamin D in animal models of sepsis improves blood coagulation parameters in disseminated intravascular coagulation and modulates levels of systemic inflammatory cytokines including TNF-α and IL-6. Vitamin D can enhance the induction of the antimicrobial peptides cathelicidin and β-defensin which are found on mucosal and epithelial surfaces and act as the body's first line of defense against viral and bacterial pathogens. Vitamin D is potentially an attractive therapeutic agent for sepsis given its low cost and low risk of toxicity and side effects. Further prospective, randomized, controlled clinical trials of adjunctive vitamin D therapy in patients who are deficient are needed in the management of human sepsis syndrome.     

维生素D缺乏与糖尿病周围神经病变的相关性研究

目的 研究2型糖尿病患者维生素D缺乏与糖尿病周围神经病变(DPN)的相关性.方法 选取2型糖尿病患者200例和正常对照者100名,其中2型糖尿病患者分为DPN组(109例)和无糖尿病周围神经病变(NDPN)组(91例).通过ELISA法测定25 (OH) D3水平,常规测定肝、肾功能,HbA1c,血脂,血钙、磷,β2微球蛋白,尿微量白蛋白等指标.25 (OH) D3与各指标之间进行相关性分析.结果 与正常对照组相比,NDPN组和DPN组25 (OH) D3水平降低,DPN组降低更加明显(F=202.265,P＜0.01),且DPN组维生素D缺乏患者比例(76.1％)明显高于NDPN组(47.3％)(x2=17.763,P＜0.01).维生素D水平与DPN、病程、年龄、性别、空腹血糖、HbA1c、总胆固醇、低密度脂蛋白-胆固醇、24 h尿微量白蛋白、β2微球蛋白均呈显著负相关(r=-0.315～-0.144,P均＜0.05),而与血钙呈正相关(r=0.193,P=0.006).二元Logistic回归分析显示,维生素D缺乏是DPN的独立危险因素(OR=3.564,95％ CI:1.950 ～6.511,P＜0.001).结论 维生素D缺乏是DPN的独立危险因子,并可能在2型糖尿病及DPN的发生、发展中发挥作用.     

亚临床甲状腺功能异常与心血管疾病的关系

临床研究显示,亚临床甲状腺功能异常与心血管疾病之间存在密切的关系.亚临床甲状腺功能减退通常伴有血脂异常、高凝状态、纤维蛋白溶解活性减低等心血管疾病危险因素,其与动脉粥样硬化、冠心病和心血管死亡的风险显著相关.另一方面,亚临床甲状腺功能亢进与心房颤动发生风险显著相关,但与心血管死亡风险的相关性尚不清楚.对于亚临床甲状腺功能异常进行治疗是否能够带来心血管获益,目前尚无确切结论.     

糖尿病患者低血糖与心血管疾病的关系

控制血糖是糖尿病治疗的首要目标,但在降糖过程中,难以避免的低血糖会减少降糖益处,甚至增加死亡风险.近年来研究发现,低血糖可以改变心血管系统神经内分泌和电生理、损害血管内皮,进而诱发糖尿病急性心血管事件或加快慢性并发症进程.低血糖的发生会抵消糖尿病患者一生高血糖治疗所带来的益处.现将低血糖与糖尿病患者心血管疾病的关系作一综述.     

Impact of vitamin D deficiency on increased blood eosinophil counts

Objective/background

Vitamin D has been increasingly recognized as an immunomodulatory agent. Its deficiency has been associated with immune-mediated diseases such as asthma, rhinitis, and atopic dermatitis. These allergic conditions are dependent on T-helper type 2 (Th2) cells secreting interleukins, overproduction of immunoglobulin E (IgE), and eosinophil activation. We investigated the association between serum vitamin D levels and blood absolute eosinophil count.

Relationship between vitamin D and inflammatory markers in older individuals

In older persons, vitamin D insufficiency and a subclinical chronic inflammatory status frequently coexist. Vitamin D has immune-modulatory and in vitro anti-inflammatory properties. However, there is inconclusive evidence about the anti-inflammatory role of vitamin D in older subjects. Thus, we investigated the hypothesis of an inverse relationship between 25-hydroxyvitamin D (25(OH)D) and inflammatory markers in a population-based study of older individuals. After excluding participants with high-sensitivity C-reactive protein (hsCRP) ≥ 10 mg/dl and those who were on chronic anti-inflammatory treatment, we evaluated 867 older adults ≥65 years from the InCHIANTI Study. Participants had complete data on serum concentrations of 25(OH)D, hsCRP, tumor necrosis factor (TNF)-α, soluble TNF-α receptors 1 and 2, interleukin (IL)-1β, IL-1 receptor antagonist, IL-10, IL-18, IL-6, and soluble IL-6 receptors (sIL6r and sgp130). Two general linear models were fit (model 1—adjusted for age, sex, and parathyroid hormone (PTH); model 2—including covariates of model 1 plus dietary and smoking habits, physical activity, ADL disability, season, osteoporosis, depressive status, and comorbidities). The mean age was 75.1 ± 17.1 years ± SD. In model 1, log(25OH-D) was significantly and inversely associated with log(IL-6) (β ± SE = −0.11 ± 0.03, p = <0.0001) and log (hsCRP) (β ± SE = −0.04 ± 0.02, p = 0.04) and positively associated with log(sIL6r) (β ± SE = 0.11 ± 0.04, p = 0.003) but not with other inflammatory markers. In model 2, log (25OH-D) remained negatively associated with log (IL-6) (β ± SE = −0.10 ± 0.03, p = 0.0001) and positively associated with log(sIL6r) (β ± SE = 0.11 ± 0.03, p = 0.004) but not with log(hsCRP) (β ± SE = −0.01 ± 0.03, p = 0.07). 25(OH)D is independently and inversely associated with IL-6 and positively with sIL6r, suggesting a potential anti-inflammatory role for vitamin D in older individuals.     

维生素D与代谢综合征

维生素D是人体必需的营养物质,其功能主要是通过维生素D受体来介导的.近年来研究发现,维生素D对胰岛具有保护作用,并且是维持正常胰岛素分泌和糖耐昔所必需的物质.临床及动物模型研究已证实维生素D对保证胰岛素正常释放以及维持糖耐量正常是必不可少的.维生素D受体基因多态性可能影响脂肪形成以及胰岛素敏感性.维生素D缺乏不仅与胰岛素抵抗和高血压的发生直接相关,而且可显著增加代谢综合征的发病风险.     

Fatigue is not associated with vitamin D deficiency in inflammatory bowel disease patients

AIM To investigate if vitamin D deficiency is associated with fatigue in patients with inflammatory bowel disease(IBD).METHODS IBD patients were recruited from nine hospitals in the southeastern and western regions of Norway to participate in a multicenter cross-sectional study lasting from March 2013 to April 2014. Data were collected by interviews, from medical records and laboratory tests. The Fatigue Questionnaire(FQ) was used to measure fatigue. Linear and logistic regression models were applied to explore the possible association between vitamin D deficiency and total fatigue scores and chronic fatigue, respectively. The analyses were adjusted for age, gender, disease activity, depressive symptoms and sleep disturbance.RESULTS In total, 405 patients were included in the analyses, of which 227(56%) had Crohn's disease(CD) and 178(44%) had ulcerative colitis(UC). Vitamin D deficiency( 50 nmol/L) was present in half(203/405) of the patients. Chronic fatigue was reported by 116(29%) of all included patients with substantial fatigue reported by 194(48%). Vitamin D levels were neither associated with total fatigue nor with chronic fatigue. Higher total fatigue scores and chronic fatigue were both associated with increased disease activity scores in patients with UC and CD, but not with increased CRP or fecal calprotectin. In UC patients, female gender was associated with fatigue in the univariate analysis, but no such difference was found when adjusted for elevated disease activity scores. Sleep disturbance and more depressive symptoms were associated with total fatigue scores in both UC and CD patients, but with chronic fatigue only in CD patients.CONCLUSION In this study, no significant association between fatigue and vitamin D deficiency in IBD patients was revealed.     

Overview of studies of the vitamin D/vitamin D receptor system in the development of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease(NAFLD) is the most common chronic liver disease in the world. NAFLD is known to be associated with obesity, type 2 diabetes, metabolic syndrome and increased cardiovascular events: for these reasons, it is becoming a global public health problem and represents an important challenge in terms of prevention and treatment. The mechanisms behind the pathogenesis of NAFLD are multiple and have not yet been completely unraveled; consequently, at moment there are not effective treatments. In the past few years a large body of evidence has been assembled that attributes an important role in hepatic aberrant fat accumulation,inflammation and fibrosis, to the vitamin D/vitamin D receptor(VD/VDR) axis,showing a strong association between hypovitaminosis D and the diagnosis of NAFLD. However, the data currently available, including clinical trials with VD supplementation, still provides a contrasting picture. The purpose of this editorial is to provide an overview of recent advances in the pathogenesis of NAFLD in relation to VD/VDR. Based on recent data from literature, we focused in particular on the hypothesis that VDR itself, independently from its traditional ligand VD, may have a crucial function in promoting hepatic fat accumulation.This might also offer new possibilities for future innovative therapeutic approaches in the management of NAFLD.