Vitamin D/vitamin D receptor, autophagy, and infection / 中南大学学报(医学版)

Vitamin D plays an important role in mineral and bone homeostasis, immune responses, cardiovascular function and keratinocyte proliferation and differentiation. Vitamin D performs most of its functions by binding to vitamin D receptors (VDR), which interact with other intracellular signaling pathways to regulate bone metabolism, inflammation, immunity, cell cycle progression and apoptosis. Autophagy is a basic stress response in yeast, plants and mammals, and plays a critical role in maintaining optimal functional states at the level of cells and organs. Vitamin D/VDR plays an anti-infection role via inducing and regulating autophagy.

Importancia de la Vitamina D en la época del COVID-19 / Importance of Vitamin D in the time of COVID-19

"Los coronavirus pertenecen a una gran familia de virus (Coronaviridae) que infectan aves y varios mamíferos. El coronavirus actualmente denominado SARS-CoV-2, fue descubierto en diciembre de 2019 en Wuhan, provincia de Hubei, China, y es el agente causal de la epidemia de neumonía atípica actual" (COVID-19; Coronavirus Disease 2019). Los casos más graves presentan un síndrome de dificultad respiratoria aguda que puede conducir a la muerte. La vitamina D (VD), además del efecto bien conocido y positivo sobre la salud ósea y la homeostasis del calcio, tiene efecto pleiotrópico en varios órganos, con distribución casi universal del receptor de VD y de las enzimas de metabolización de 25 hidroxivitamina D (25OHD) en las células del organismo. Estas acciones extraesqueléticas dependen de la síntesis en dichas células del metabolito activo 1,25 dihidroxivitamina D por regulación paracrina y autocrina, dependiente de niveles circulantes óptimos de 25OHD. Por sus acciones inmunomoduladora, antiinflamatoria, antimicrobiana, reguladora del sistema renina-angiotensina-aldosterona, favorecedora de la indemnidad del epitelio respiratorio y la homeostasis redox celular, la VD podría tener efecto protector en la infección por COVID-19. Entre los grupos de riesgo para COVID-19 figuran los adultos mayores, obesos, diabéticos, hipertensos, con afecciones cardiovasculares, patologías con mayor incidencia en individuos con hipovitaminosis VD. La suplementación con VD, para alcanzar niveles óptimos de 25OHD de 40-60 ng/ml, podría reducir la incidencia, severidad y riesgo de muerte en la actual pandemia por COVID-19, como medida complementaria mientras se desarrollan la vacuna y otras medicaciones específicas. (AU)

Coronaviruses belong to a large family of viruses (Coronaviridae) that infect birds and various mammals. The novel coronavirus currently known as SARS-CoV-2 was discovered in December 2019 in Wuhan, Hubei province, China and is the causal agent of the current atypical pneumonia epidemic (COVID-19: Coronavirus Disease 2019); The most severe cases present with acute respiratory distress syndrome that can lead to death. Vitamin D (VD) has a pleiotropic effect on several organs, in addition to its wellknown and positive effect on bone health and calcium homeostasis, with an almost universal distribution of the VD receptor and the metabolites of 25hydroxyvitamin D (25OHD) in all cells of the body. These extra-skeletal actions depend on the synthesis of the active metabolite 1,25dihydroxyvitamin D in the cells depending on the optimal circulating levels of 25OHD and though paracrine and autocrine regulation. Due to its immunomodulatory, anti-inflammatory, antimicrobial, and regulatory actions on the renin angiotensin aldosterone system, which favors the compensation of the respiratory epithelium and cellular redox homeostasis, the VD could have a protective effect on COVID-19 infection. Among the risk groups for COVID-19 are obese, diabetic, and hypertensive patients, subjects with cardiovascular conditions, and elderly people. All these pathologies show a higher incidence in individuals with VD hypovitaminosis. VD supplementation, to achieve optimal 25OHD levels of 40-60 ng/ml, could reduce the incidence, severity, and risk of death in the current COVID-19 pandemic, as a complementary measure while the vaccine and other specific therapies are being developed. (AU)

Vitamina D y enfermedades respiratorias pediátricas / Vitamin D and pediatrics respiratory diseases

Resumen: El mejor entendimiento sobre la actividad global de la vitamina D, ha llevado a una intensa búsque da de sus implicancias en enfermedades no esqueléticas. En este artículo se presenta una revisión actualizada de la relación entre la vitamina D y la patología respiratoria pediátrica. Se realizó una búsqueda bibliográfica en PUBMED utilizando términos libres y MESH: vitamina D, enfermedades del sistema respiratorio, asma, bronquiolitis. Se seleccionó estudios en humanos menores de 18 años y animales, publicados en inglés y español hasta el 2017. Se encontraron 507 artículos, de los cuales se incluyeron 43. Evidencia indirecta apunta hacia un rol de la vitamina D y la maduración pulmonar fetal. En relación a la patología pulmonar pediátrica, los estudios son escasos y poco concluyentes. Nuevos meta - análisis, con evaluación individualizada de los participantes, muestran un importante rol protector de la suplementación en la prevención de exacerbaciones asmáticas severas e infecciones virales agudas. En bronquiolitis los resultados son contradictorios, sin relación clara entre niveles plasmáticos y severidad. No existe suficiente evidencia que evalué los beneficios en fibrosis quística y tuberculosis. Recientemente se ha propuesto una relación directa entre la severidad de los trastornos respiratorios del sueño y los niveles plasmáticos de vitamina D, aunque se desconoce los mecanismos exactos involucrados a esta asociación. La información actual permite suponer que la suplementación de vitamina D puede representar una estrategia costo - efectiva en la reducción de importantes causas de morbimortalidad infantil.

Abstract: The better understanding of the global activity of vitamin D has led to an intense search for its involvement in non-skeletal diseases. This article presents an updated review of the relationship between vitamin D and pediatric respiratory pathology. A literature search was performed in PUBMED using free terms and MESH terms: vitamin D, asthma, respiratory system diseases, and bronchiolitis. Stu dies in human patients younger than 18 years and animals, published in English and Spanish until 2017 were included. 507 articles were found, of which 43 were included. Indirect evidence suggests a role of vitamin D and fetal lung maturation. In relation to pediatric pulmonary pathology, studies are scarce and inconclusive. Recent meta-analyses performed with individualized evaluation of the participants shows an important protective role of vitamin D supplementation in the prevention of severe asthma exacerbations and acute viral infections. In bronchiolitis, the results are contradictory, with no clear relationship between plasma levels and severity. There is not enough evidence to assess the benefits of vitamin D supplementation in cystic fibrosis and tuberculosis. A direct relationship between the severity of sleep-related breathing disorders and vitamin D plasma levels has recently been proposed, although the exact mechanisms involved in this association are unknown. Current information suggests that vitamin D supplementation may represent a cost-effective strategy in redu cing important causes of infant morbidity and mortality.

Niveles de 25(oh)-vitamina D en pacientes con diabetes mellitus tipo 2 con y sin síndrome metabólico / 25(OH)-Vitamin D levels in type 2 diabetes with and without metabolic syndrome

Los bajos niveles de 25-hidroxivitamina D (25OHD) se han vinculado con el desarrollo de enfermedad cardiovascular, diabetes mellitus tipo 2, obesidad, dislipidemia e hipertensión arterial, todos componentes del síndrome metabólico (SM). Además, se ha reportado una asociación inversa entre 25OHD y el SM, resistencia a la insulina, deterioro de la función celular ß e intolerancia a la glucosa. El objetivo de este trabajo fue evaluar los niveles de 25OHD en pacientes diabéticos tipo 2 con y sin SM. Se llevó a cabo un estudio observacional de corte transversal. Se evaluaron 108 pacientes diabéticos tipo 2 (grupo DM2) y 89 pacientes sin DM2 (GC) con y sin SM, en los cuales se determinó la concentración de 25OHD total. Se calculó el cociente de probabilidad (OR) e intervalo de confianza del 95% (IC95) para la deficiencia de 25OHD (<20 ng/ml). Resultados: el grupo DM2 presentó niveles menores de 25OHD (19,8 ng/ml vs. 25,0 ng/ml) y mayor proporción de pacientes con deficiencia de 25OHD respecto del GC (50,9% vs. 28,1%, OR 2,7, IC95%: 1,5-4,8). No se halló una correlación entre 25OHD y HbA1c. Se halló asociación significativa entre deficiencia de 25OHD y presencia de diabetes, obesidad y SM. Sin embargo, en el análisis multivariado solo la presencia del SM presentó asociación negativa significativa con la deficiencia de 25OHD (OR=4,04, IC95% 1,48-11,68). En conclusión, nuestros datos demuestran una elevada prevalencia de hipovitaminosis D en pacientes con diabetes mellitus tipo 2 a expensas, principalmente, del elevado porcentaje de pacientes que padecen SM. El SM incrementa cuatro veces el riesgo de deficiencia de vitamina D independientemente de la presencia de diabetes mellitus tipo 2. (AU)

Low levels of 25-hydroxyvitamin D (25OHD) have been linked to cardiovascular disease, type 2 diabetes mellitus, obesity, dyslipidemia and hypertension, all components of the metabolic syndrome. An inverse association has been observed between 25OHD and metabolic syndrome, insulin resistance, impaired ß-cell function and glucose intolerance. The aim of this study was to evaluate the 25OHD levels in type 2 diabetic patients with and without metabolic syndrome. An observational cross-sectional study was carried out. We included 108 type 2 diabetic patients (DM2 group) and 89 patients without DM2 (CG) with and without metabolic syndrome, in which the total 25OHD levels were measured. The odds ratio (OR) and 95% confidence interval (95%CI) for 25OHD deficiency (<20 ng/ml) were estimated. Results: The DM2 group had lower 25OHD levels (19.8 ng/ml vs 25.0 ng/ml) and higher proportion of patients with a 25OHD deficiency compared to the CG (50.9% vs 28.1%, OR 2.7, 95%CI: 1.5-4.8). No correlation was found between 25OHD and HbA1c. A significant association was found between 25OHD deficiency and the presence of diabetes, obesity, and the presence of metabolic syndrome. However, in the multivariate analysis only the presence of metabolic syndrome had a significant negative association with the 25OHD deficiency (OR=4.04, 95%CI 1.48-11.68). In conclusion, we found a high prevalence of hypovitaminosis D in DM2 and the metabolic syndrome increases the risk of 25OHD deficiency by four times. (AU)

Effect of Vitamin D supplementation on reduction in levels of HbA1 in patients recently diagnosed with type 2 Diabetes Mellitus having asymptomatic Vitamin D deficiency

Objective: To study the effect of Vitamin D supplementation on reduction in level of HbA1 in patients recently diagnosed with diabetes mellitus Type II having asymptomatic Vitamin D deficiency

Methods: This randomized control trial was conducted at East Medical Ward Mayo Hospital Lahore for 6 months from January 01 2016 to June 30, 2016. 114 Patients were included through non probability purposive sampling technique. Informed consent and demographic information was collected. Patients were divided in two groups by randomization through tossing a coin. GroupA patients received Metformin tablet alone at 500 mg after dinner and Group-B patients were treated with same dosage of Metformin along with oral vitamin D at 200,000 ILJ monthly for three months. Blood sample was obtained at baseline, 3 months and 6 months of initiation of therapy. All samples were sent to the laboratory for complete blood count, blood sugar fasting, serum calcium, serum phosphorous, serum alkaline phosphatase, HbA1c and serum 25 Hyroxy Vitamin D [S-25[OH] D] levels and iPTH. Data entry and analysis was done by using SPSS 20

Results: The mean age of patients in metformin group was 42.37+/-4.59 years while mean age of patients in combination group was 43.33+/-4.86years. Males were 45.6% and females were 54.4% in metformin group while in combination group, 36.8% were males1 and 63.2% were females'. At baseline, in metformin group, mean Vitamin D level was 17.09+/-1.73mg/dl and in combination group, mean Vitamin D level was 16.49+/-n D was 29.04+/-3.96mg/dl. At baseline, 1[st] and 2[nd] visit, in metformin group, mean HbA1c was 7.59+/-0.47%, 7.46+/-0.25% and 7.30+/-0.29%. At baseline, 1[st] and 2[nd] visit, in combination group, mean HbA1c was 7.71 +/-0.19%, 7.57+/-0.21% and 7.43+/-0.26%. The difference was insignificant [p>0.05] at baseline while significant on later follow-ups [P<0.05]

Conclusion: Vitamin D supplementation improved the glycemic control but substantial reduction in HbA1c was statistically insignificant in both groups

Vitamina D na modulação da microbiota intestinal: associações com os perfis inflamatório e cardiometabólico / Vitamin D in intestinal microbiota modulation: associations with inflammatory and cardiometabolic profiles

Introdução: Bactérias intestinais influenciam a resposta imune e conhecendo-se as ações imunomoduladoras da vitamina D passou-se a investigar sua relação com a microbiota. O status adequado desta vitamina está associado a uma composição mais saudável da microbiota, enquanto sua deficiência pode acarretar disbiose intestinal, endotoxemia, inflamação e resistência à insulina. O conhecimento de interações do status de vitamina D com a microbiota pode melhorar a compreensão da gênese de doenças crônicas mediadas pela inflamação. Objetivo: Examinou-se a associação da ingestão e concentração de vitamina D com a composição da microbiota fecal, marcadores inflamatórios e perfil bioquímico de participantes do Nutritionists Health Study. Métodos: Nesta análise transversal, 150 adultos jovens foram estratificados em tercis de consumo e de concentração de 25(OH)D e comparados quanto ao perfil clínico e inflamatório. A associação de 25(OH)D com a microbiota (sequenciamento do 16S rRNA, região V4, Illumina® MiSeq) foi testada por regressão linear múltipla. Resultados: A ingestão de vitamina D se associou aos níveis séricos (p < 0,05). Não foram observadas diferenças significantes de variáveis clínicas e inflamatórias entre os tercis de ingestão, exceto tendência de aumento do LPS com a redução da 25(OH)D (p-trend < 0,05). Prevotella foi mais abundante (log2FC 1,67; p < 0,01), e Haemophilus and Veillonella menos abundantes (log2FC -2,92 e -1,46; p < 0,01, respectivamente) no subgrupo com maior ingestão de vitamina D (referência) comparado aos outros grupos (primeiro e segundo tercis). PCR (r = -0,170; p = 0,039), selectina-E (r = -0,220; p = 0,007) e abundância de Coprococcus (r = -0,215; p = 0,008) e de Bifdobacterium (r = -0,269; p = 0,001) foram inversamente correlacionados com 25(OH)D. Após ajustes por idade, sexo, estação do ano e IMC, a 25(OH)D manteve associação inversa com Coprococcus ( = -9,414; p = 0,045) e Bifdobacterium ( = -1,881; p = 0,051), mas a significância desapareceu com a adição de marcadores inflamatórios aos modelos. Conclusão: Associações de ingestão e concentração de vitamina D com abundância de certos gêneros da microbiota sugerem que sua ação imunomoduladora poderia influenciar a composição bacteriana. Abundância relativamente maior de gram-negativos (Haemophilus e Veillonella) pode ter sido facilitada pela baixa ingestão e/ou concentração da vitamina. Menor proporção de bactérias benéficas (Coprococcus e Bifidobacterium) poderia estimular a resposta imune e inflamação. Concluímos que a participação da vitamina D na manutenção da homeostase imune deve ocorrer em parte pelas interações com a microbiota intestinal, embora o delineamento transversal impeça assegurar relações tipo causa-efeito

Introduction: Gut bacteria influence the immune response and due the immunomodulatory actions of vitamin D, it has been investigated its relationship with the microbiota. Adequate status of this vitamin is associated with adequate composition of the microbiota, while its deficiency can cause gut dysbiosis, endotoxemia, inflammation and insulin resistance. The knowledge of interactions of vitamin D status with the microbiota may improve the understanding of the genesis of inflammation-mediated chronic diseases. Objective: We examined the association of vitamin D intake and concentration with the composition of fecal microbiota, inflammatory markers and biochemical profile of participants from the Nutritionists' Health Study. Methods: In this cross-sectional analysis, 150 healthy young adults were stratified into tertiles of intake and concentrations of vitamin D and their clinical and inflammatory profiles were compared. The association between 25(OH)D and fecal microbiota (16S rRNA sequencing, V4 region, Illumina® MiSeq) was tested by multiple linear regression.) Results: Vitamin D intake was associated with its concentration (p<0.05). There were no significant differences in clinical and inflammatory variables across tertiles of intake, except for a trend of LPS increases with reduction of 25(OH)D (p-trend <0.05). Prevotella was more abundant (log2FC 1.67; p <0.01), and Haemophilus and Veillonella less abundant (log2FC -2,92 e -1.46; p <0.01, respectively) in subset with the highest vitamin D intake (reference) than that observed in the other subset (first plus second tertiles). CRP (r=-0.170, p=0.039), E-selectin (r=-0.220, p=0.007) and abundances of Coprococcus (r=-0.215, p=0.008) and Bifdobacterium (r=-0.269, p=0.001) were inversely correlated with 25(OH)D. After adjusting for age, sex, season and BMI, the 25(OH)D maintained inversely associated with Coprococcus (=-9.414, p=0.045) and Bifdobacterium (=-1.881, p=0.051), but significance disappeared following the addition of inflammatory markers in the regression models. Conclusion: Association of vitamin D intake and concentration with abundance of certain genera of microbiota suggests that its immunomodulatory action could influence the bacterial composition. Relatively higher abundance of gram-negative (Haemophilus and Veillonella) may have been facilitated by the low intake and/or concentration of the vitamin. Lower proportion of beneficial bacteria (Coprococcus and Bifidobacterium) could stimulate the immune response and inflammation. We conclude that the role of vitamin D in maintaining immune homeostasis should occur in part by interactions with the gut microbiota, although the cross-sectional design does not allow ensuring cause-effect relationships

The role of daily physical activity and nutritional status on bone turnover in cystic fibrosis: a cross-sectional study

ABSTRACT Background Nutritional status and daily physical activity (PA) may be an excellent tool for the maintenance of bone health in patients with cystic fibrosis (CF). Objective To evaluate the relationship between nutritional status, daily physical activity and bone turnover in cystic fibrosis patients. Method A cross-sectional study of adolescent and adult patients diagnosed with clinically stable cystic fibrosis was conducted. Total body, femoral neck, and lumbar spine bone mineral density (BMD) were determined by dual energy X-ray absorptiometry and bone metabolism markers ALP, P1NP, PICP, and ß-CrossLaps. PA monitoring was assessed for 5 consecutive days using a portable device. Exercise capacity was also determined. Serum 25-hydroxyvitamin D and vitamin K were also determined in all participants. Results Fifty patients (median age: 24.4 years; range: 16-46) were included. BMI had positive correlation with all BMD parameters, with Spearman’s coefficients ranging from 0.31 to 0.47. Total hip bone mineral density and femoral neck BMD had positive correlation with the daily time spent on moderate PA (>4.8 metabolic equivalent-minutes/day; r=0.74, p<0.001 and r=0.72 p<0.001 respectively), daily time spent on vigorous PA (>7.2 metabolic equivalent-minutes/day; r=0.45 p<0.001), body mass index (r=0.44, p=0.001), and muscle mass in limbs (r=0.41, p=0.004). Levels of carboxy-terminal propeptide of type 1 collagen were positively associated with the daily time spent on moderate (r=0.33 p=0.023) and vigorous PA (r=0.53, p<0.001). Conclusions BMI and the daily time spent on moderate PA were found to be correlated with femoral neck BMD in CF patients. The association between daily PA and biochemical markers of bone formation suggests that the level of daily PA may be linked to bone health in this patient group. Further research is needed to confirm these findings.

Osteoporose na artrite reumatoide: papel do sistema vitamina D/hormônio paratireóideo / Osteoporosis in rheumatoid arthritis: role of the vitamin D/parathyroid hormone system

A osteoporose é uma característica extra-articular bem estabelecida da artrite reumatoide (AR). A inflamação sistêmica parece ser essencial para causar uma alteração em múltiplos sistemas homeostáticos implicados na saúde óssea, como as vias RANK/RANKL/osteoprotegerina e Wnt/β catenina; vários outros fatores causais têm sido implicados, como o uso crônico de corticosteroides. Como a vitamina D exerce funções imunorreguladoras importantes, tem-se afirmado que o desarranjo do sistema vitamina D/hormônio paratireóideo (HPT), um determinante bem conhecido da saúde óssea, pode desempenhar um papel patogênico na autoimunidade; estudos com animais e dados clínicos apoiam essa hipótese. Além disso, os pacientes com AR parecem ser relativamente refratários à supressão de HPT induzida pela vitamina D. Portanto, a ligação entre a AR e a osteoporose pode ser em parte causada por alterações no sistema vitamina D/HPT. Uma melhor compreensão da fisiopatologia desse sistema pode ser crucial para prevenir e curar a osteoporose em pacientes com doenças inflamatórias/autoimunes. A maior evidência da correlação clínica de cooperação e interdependência entre a vitamina D e o HPT é que a correção da deficiência de vitamina D, pelo menos nas doenças autoimunes, deve ser orientada para a supressão do HPT.

Osteoporosis is a well-established extra-articular feature of rheumatoid arthritis (RA). Systemic inflammation seems to play a crucial role in causing an alteration of multiple homeostatic systems implied in bone health, such as the RANK/RANKL/Osteoprotegerin and Wnt/β catenin pathways; several other causal factors have been called into question, including the chronic use of corticosteroids. Since vitamin D exerts important immune-regulatory roles, it has been claimed that derangement of the vitamin D/parathyroid hormone (PTH) system, a well-known determinant of bone health, may play a pathogenic role in autoimmunity; animal models and clinical data support this hypothesis. Furthermore, RA patients seem to be relatively refractory to vitamin D-induced PTH suppression. Therefore, the link between RA and osteoporosis might in part be due to alterations in the vitamin D/PTH system. A better understanding of the pathophysiology of this system may be crucial to prevent and cure osteoporosis in patients with inflammatory/autoimmune diseases. A major clinical correlate of the strict cooperation and interdependence between vitamin D and PTH is that correction of the vitamin D deficiency, at least in autoimmune diseases, should be targeted to PTH suppression.

Influencia de la vitamina D en la salud humana / Influence of vitamin D in human health / Influência da vitamina D na saúde humana

La vitamina D es una sustancia liposoluble, que tiene dos formas: ergocalciferol (vitamina D2) o colecalciferol (vitamina D3), que se encuentran en algunas plantas y peces, y son sintetizadas en la piel a través de la luz del sol respectivamente. La deficiencia de esta vitamina puede ayudar en la aparición y agravamiento de muchas enfermedades. La deficiencia de vitamina D es común en personas de edad avanzada, sin embargo, puede estar presente en cualquier edad y se asocia con las enfermedades cardiovasculares, las enfermedades autoinmunes, el cáncer y las enfermedades metabólicas. La producción de vitamina D en la piel es modulada por la estación, la latitud, la hora del día, pigmentación de la piel, la edad y el uso de protectores solares. Su forma activa 1,25(OH)2D ejerce diversas funciones en el cuerpo, tales como la salud ósea, la homeostasis, el metabolismo celular, la regulación del sistema inmunológico, cardiovascular y sistema esquelético. En la actualidad, la falta se considera como un problema de salud pública en todo el mundo.

Vitamin D is a liposoluble substance, which has two forms: ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3), found in some plants and fish, or synthesized in the skin through sunlight, respectively. Deficiency of this vitamin may help to the onset and worsening of many diseases. Hypovitaminosis D is prevalent in the elderly, but can be present at any age, and is associated with cardiovascular diseases, autoimmune diseases, cancer and metabolic diseases. The skin vitamin D production is modulated by the season, latitude, time of day, skin pigmentation, age and use of sunscreen. Its active form 1,25(OH)2D exerts several functions in the body such as bone health, homeostasis, cell metabolism, immune system regulation, cardiovascular and skeletal systems. Currently, its lack is seen as a public health problem worldwide.

A vitamina D é uma substância lipossolúvel, que se apresenta de duas formas: ergocalciferol (vitamina D2) ou colecalciferol (vitamina D3), encontrada em plantas e alguns peixes, ou sintetizada na pele através da luz solar, respectivamente. A deficiência desta vitamina pode auxiliar no aparecimento e agravamento de diversas patologias. A hipovitaminose D é prevalente em indivíduos idosos, contudo, pode estar presente em qualquer faixa etária e está relacionada com doenças cardiovasculares, doenças autoimunes, câncer e doenças metabólicas. A produção cutânea de vitamina D é modulada pela estação, latitude, período do dia, pigmentação da pele, idade e uso de filtro solar. Sua forma ativa 1,25(OH)2D exerce diversas funções no organismo, como na saúde óssea, homeostasia, metabolismo celular, regulação do sistema imune, cardiovascular e esquelético. Atualmente, sua deficiência é vista como um problema de saúde pública em todo o mundo.

Vitamina D e diabetes mellitus, suas epidemias e o envelhecimento. O que há de novo? / Vitamin D and diabetes mellitus, their epidemics and the aging. What is new?

O diabetes mellitus do tipo 2, um problema de saúde pública, tem seu diagnóstico e tratamento negligenciados na prática clínica. Embora a abordagem terapêutica tenha avançado nas últimas décadas por meio da melhor compreensão de sua fisiopatologia e do desenvolvimento de fármacos que atuam nas diversas etapas dessa doença, o aumento de novos casos suscita a necessidade do conhecimento de outros alvos terapêuticos e de intervenções clínicas para a prevenção e o tratamento dessa doença. Evidências acumuladas em estudos transversais e longitudinais sugerem uma potencial participação da vitamina D na fisiopatologia do diabetes. Entretanto, os resultados são baseados em estudos clínicos com pequenas amostras, além de não considerar populações específicas, como, por exemplo, mulheres na pós-menopausa, nem tampouco qual o nível de suplementação que deve ser ofertado para uma resposta clínica satisfatória. Com o aumento da expectativa de vida, a detecção precoce, o tratamento e a amenização de quaisquer distúrbios ou doenças que comprometam a qualidade de vida ou afetem os índices de morbimortalidade são essenciais para a melhoria da qualidade de vida. Fazemos uma atualização dessas duas epidemias no contexto de vida da mulher pós-menopausa e das possíveis participações da vitamina D na fisiopatologia do diabetes mellitus do tipo 2.

Type 2 diabetes has been an of public health concern and therefore has its diagnosis and treatment delayed in clinical practice. Although, its treatment has improved in the last decades by better pathophysiology understanding and development of medicines that actin different phases and levels, the increase of new cases of diabetes claim for knowledge about newest terapheutics targets in order to prevent and treat this disease. Accumulatedevidences from crossover and longitudinal studies suggested a potencial participation ofVitamin D in diabetes pathophysiology. However, the results are based on clinical studies with a few sample and do not consider specifical populations like post menopausal womenas did not determine dose of vitamin D that need to be offered. Early diagnosis, treatment and relieve of disorders and diseases that compromise the quality of life are extremely usefull in face to longest aging. We bring up an atualization about how vitamin D could take part on diabetes pathophysiology and some studies results.

Deficiência de vitamina D em indivíduos HIV-positivos expostos ou não a esquemas antirretrovirais: um estudo transversal / Vitamin D deficiency in HIV-positive individuals exposed or not to antiretroviral regimens: a cross sectional study

A deficiência de vitamina D é uma condição subdiagnosticada e geralmente não aventada como alvo de investigação laboratorial por parte dos clínicos. Estima-se que em torno de 36 por cento dos adultos saudáveis e 57 por cento dos pacientes internados apresentem algum grau de deficiência de vitamina D. A prevalência elevada desta deficiência deve-se aos polimorfismos dos genes implicados na resposta à vitamina D, baixa exposição solar, interações medicamentosas e aspectos nutricionais. A aplicação das pesquisas relacionadas à vitamina D e AIDS se baseia em possíveis usos na redução da transmissibilidade, redução da progressão clínica, interações medicamentosas, redução na incidência de infecções, neoplasias, doenças autoimunes e queda da mortalidade geral. Este estudo visa obter a prevalência da deficiência de vitamina D entre em pacientes com diagnóstico de infecção pelo HIV acompanhados em um grande ambulatório de referência no município do Rio de Janeiro, avaliar a associação do uso de antirretrovirais e deficiência de vitamina D, associação entre a contagem de linfócitos TCD4+ e a deficiência de vitamina D, associação entre a carga viral plasmática do HIV e a deficiência de vitamina D e realizar a análise estatística dos dados utilizando técnicas descritivas e exploratórias. Dos pacientes estudados, um total de 91 (72,8 por cento) apresentou deficiência de vitamina D, definida por concentração plasmática inferior a 32 ng/dLO grupo foi classificado categoricamente em deficiência grave, com valores inferiores a 10 ng/dL (5 indivíduos), deficiência moderada, entre 10-19 ± (36 indivíduos), deficiência leve, 20-31 ng/dL (50 indivíduos) e suficiência, maiores ou iguais a 32 ng/dL (34 indivíduos). Não foi encontrada associação entre as concentrações plasmáticas de vitamina D e as variáveis idade, sexo, tempo de diagnóstico, tempo de uso de terapia antirretroviral, carga viral plasmática do HIV e esquema antirretroviral atual...

The vitamin D deficiency is an underdiagnosed condition and generally not investigated by the clinical laboratory. It is estimated that around 36 percent of healthy adults and 57 percent of hospitalized patients in the U.S. have some degree of vitamin D defiency. The high prevalence of this condition is due to polymorphisms of genes involved in the response to vitamin D, low sunexposure, drug interactions, and nutritional aspects. The application of research related to vitamin D and AIDS is based on possible uses: reduction intransmission, reduction in clinical progression, drug interactions, reducedincidence of infections, malignancies, autoimmune diseases, and decreasedoverall mortality. This study aims to determine the prevalence of vitamin Ddeficiency among patients diagnosed with HIV infection followed at a greatreference outpatient clinic in the city of Rio de Janeiro, assess the associationbetween use of antiretroviral drugs and vitamin D deficiency, associationbetween CD4 + lymphocyte count and vitamin D, between plasma HIV viralload and vitamin D deficiency, and perform statistical analysis of the data using descriptive and exploratory techniques. Of the patients studied, a total of 91 (72.8 percent) had vitamin D defiency, defined as plasma concentration below 32 ng /dL. The group was rated categorically in severe defiency with less than 10 ng /dL (5 subjects), moderate defiency , between 10-19 ± (36 subjects) , milddefiency, 20-31 ng / dL (50 individuals), and sufficiency, greater than or equal to 32 ng / dL (34 individuals) . No association was found between plasma concentrations of vitamin D and the variables age, sex, time since diagnosis, duration of use of antiretroviral therapy, plasma HIV viral load, and current antiretroviral regimen...

Vitamina D: ações extraósseas e uso racional / Vitamin D: non-skeletal actions and rational use

O número de dosagens do nível sérico de vitamina D tem apresentado crescimento muito expressivo nos últimos anos em todo o mundo. No Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo houve aumento de cerca de 700% em quatro anos nas solicitações desse hormônio. No entanto, há controvérsias na literatura sobre a real utilidade de sua dosagem e/ou suplementação, exceto em situações diretamente relacionadas ao metabolismo ósseo. No presente trabalho são revistos o metabolismo, as fontes e as ações da vitamina D no organismo. Estudos observacionais, ensaios clínicos, revisões sistemáticas e metanálises, cujo foco é a relação entre vitamina D e doenças ou condições clínicas, como câncer, doenças cardiovasculares, diabetes e quedas, foram pesquisados na literatura, analisados e discutidos. Os resultados estão apresentados em forma de perguntas e respostas, tabelas e figura. Discute-se o papel da vitamina D em todas essas situações, e salientam-se os pontos controvertidos.

Recent years have witnessed a substantial increase in the number of seric determinations of vitamin D, in aworldwide basis. At Hospital das Clínicas of Faculdade de Medicina of Universidade de São Paulo that increase reached 700% over the last four years. Nevertheless there are many controversies on the literature about the role of vitamin D in conditions unrelated to themusculoskeletal system. In this study the metabolism, sources and actions of vitamin D on the body are reviewed. Observational studies, clinical trials, systematic reviews and metanalysis which focused on the relationship between the vitamin and conditions such as cancer, cardiovascular disease, diabetes and falls were searched on the literature, analyzed and discussed. Results are presented as quiz and answer, tables and a figure. The role of vitamin D on the above-mentioned conditions is discussed, and the controversial issues stressed.

Vitamina D y cáncer: acción antineoplásica de la 1α, 25(OH)2 -vitamina D3 / Vitamin D and cancer: antineoplastic effects of 1α,25(OH)2-vitamin D3

La forma hormonalmente activa de la vitamina D, 1α,25(OH)2-vitamina D3 (1α,25(OH)2D3), además de desempeñar un rol crucial en el mantenimiento de la homeostasis de calcio en el cuerpo, también regula el crecimiento y la diferenciación de diferentes tipos celulares, incluyendo células cancerosas. Actualmente hay numerosos estudios que investigan los efectos de la hormona en estas células, debido al interés en el uso terapéutico del 1α,25(OH)2D3 y de análogos con menor actividad calcémica para el tratamiento o prevención del cáncer. En este trabajo de revisión se describe el sistema endocrino de la vitamina D, su mecanismo de acción, su acción antineoplásica y se provee información sobre los últimos avances en el estudio de nuevos análogos de la hormona con menos actividad calcémica para el tratamiento del cáncer.

The hormonal form of vitamin D, 1α,25(OH)2-vitamin D3 (1α,25(OH)2D3), in addition of playing a central role in the control of calcium homeostasis in the body, regulates the growth and differentiation of different cell types, including cancer cells. At present several epidemiologic and clinical studies investigate the effect of the hormone in these cells due to the interest in the therapeutic use of 1α,25(OH)2D3 and analogues with less calcemic activity for prevention or treatment of cancer. This review describes vitamin D endocrine system, its mechanism of action, its antineoplastic activity and provides information about the latest advances in the study of new hormone analogues with less calcemic activity for cancer treatment.

Hipocalcemia: complicación en cirugía endocrino-metabólica: a propósito de un caso / Hypocalcemia: complication in surgery endrocrine-metabolica: a purpose of a case

La hipocalcemia es una complicación metabólica común en la tiroidectomía total y en el bypass gástrico. El mecanismo que la provoca es diferente en ambas entidades clínicas. La incidencia de esta complicación es variable, la presentación clínica es inespecífica y el manejo farmacológico no está estandarizado. Se presenta el caso clínico de una paciente de 40 años, a la cual se le realizaron ambas cirugías con el desarrollo de hipocalcemia sintomática post-operatoria.

Hypocalcemia is a common metabolic complications in total thyroidectomy and gastric bypass. The mechanism that causes it is different in both clinical entities. The incidence of this complication is variable, the clinical presentation is nonspecific and pharmacological management is not standardized. A case report of a patient of 40 years which were performed both surgeries with the development of postoperative symptomatic hypocalcemia.

Evidence-based non-skeletal actions of vitamin D / Evidências das ações não esqueléticas da vitamina D

Vitamin D is a major regulator of mineral homeostasis through its action in the kidney, intestine, bone and parathyroid glands. On these tissues, its active form, calcitriol, acts by binding to a specific nuclear receptor that belongs to the steroid/thyroid hormone receptor family. This receptor, however, has also been identified in several additional human tissues. So, apart from its traditional actions related to calcium, vitamin D and its synthetic analogs are being increasingly recognized for their anti-proliferative, pro-differentiative and immunomodulatory activities. Low levels of vitamin D have been linked to many chronic diseases. Decreased muscle function and increased fall risk in elderly people; prostate, breast and colorectal cancers; diabetes mellitus; and other health problems have been associated to low circulating levels of 25-hydroxyvitamin D. This paper presents an overview of the available scientific evidence for the non-calcemic actions of vitamin D in humans.

A vitamina D é um importante regulador da homeostase mineral por meio de sua ação nos rins, no intestino, nos ossos e nas glândulas paratireoides. Nesses tecidos, sua forma ativa, o calcitriol, atua ligando-se a um receptor nuclear específico, pertencente à família de receptores dos hormônios esteroides e tireoidianos. Contudo, esse receptor também foi identificado em outros tecidos humanos. Assim, além de suas ações tradicionais, relacionadas ao metabolismo do cálcio, a vitamina D e análogos sintéticos estão, cada vez mais, sendo reconhecidos por seus efeitos antiproliferativos, pró-diferenciação e imunomodulatórios. Baixas concentrações séricas de vitamina D têm sido associadas a várias doenças crônicas. Redução da função muscular e aumento do risco de quedas em idosos; câncer de próstata, mama e colorretal; diabetes melito; e outros problemas de saúde têm sido associados a concentrações circulantes baixas de 25-hidroxivitamina D. Este trabalho apresenta uma visão geral sobre as evidências científicas disponíveis das ações não calcêmicas da vitamina D em humanos.

The physiology of vitamin D : current concepts.

The vitamin D endocrine system, besides playing pivotal roles in calcium homeostasis & bone mineral metabolism, is now recognized to subserve a wide range of fundamental biological functions in cell differentiation, inhibition of cell growth as well as immuno modulation. Vitamin D is a prohormone which is converted into its active hormonal form 1, 25 (OH)D2 D, 1, 25 (OH)D2 D activates its cellular receptor (VDR) which activate target genes to engender its biological actions. This review provides a summary of recent understanding of the complex actions of the vitamin D hormone 1, 25 (OH)2 D which is a final product of 1alpha hydroxylation in the proximal tubular cells of kidneys. Emerging evidence also indicates both 1, 25 (OH)2 D3 independent as well as depended action of vitamin D receptor (VDR). Thus, the vitamin D system action may involve more than one single receptor and legand. The presence of 1alpha hydroxylase in many target cells other than proximal renal tubular cells indicates autocrine and paracrine functions for 1, 25 (OH)2 D3 in the control of cell proliferation and differentiation. Vitamin D and related molecules belong to a elaborate endocrine system that acts on target genomic receptors in several organ systems to control cell proliferation and differentiation.