RESUMO
Tightly regulated iron metabolism prevents oxidative stress. Hepcidin is a hormone that regulates iron flow in plasma; its production is induced by an iron overload and by inflammation. It inhibits iron entry into the circulation by blocking dietary absorption in the duodenum, the release of recycled iron from macrophages and the exit of stored iron from hepatocytes. Varied signals responding to iron stores, erythropoietic activity and host defense converge to regulate hepcidin production and thereby affect iron homeostasis. Although it is known that hepcidin increases when interleukin 6 (IL-6) increases, the relationship between hepcidin, dyslipidemia, insulin resistance (IR) and visceral adiposity index (VAI) in adolescents with obesity is unclear. In this cross-sectional study of 29 obese adolescents and 30 control subjects, we explored the difference of hepcidin, iron metabolism markers and IL-6 between obese and non-obese adolescents, and identified associations with inflammation, atherogenic dyslipidemia and IR. As compared to lean controls, obese participants showed 67% higher hepcidin: 14,070.8 ± 7213.5 vs. 8419.1 ± 4826.1 pg/mLc; 70% higher ferritin: 94.4 ± 82.4 vs. 55.1 ± 39.6 pg/mLa and 120% higher IL-6: 2.0 (1.1-4.9) vs. 0.9 (0.5-1.3) pg/mLd. Transferrin, soluble transferrin receptor and total body iron (as measured by sTFR/ferritin, log10 sTFR/ferritin ratio and sTFR/log ferritin ratios) were not different between the two cohorts. In the whole cohort, hepcidin correlated with VAI (r = 0.29a), sd-LDL (r = 0.31b), HOMA-IR (r = 0.29a) and IL-6 (r = 0.35c). In obese adolescents hepcidin correlated with TG (r = 0.47b), VLDL-C (r = 0.43b) and smaller LDL2 (r = 0.39a). Hepcidin elevation in adolescents with obesity is linked more to inflammation and metabolic alterations than to iron metabolism since the other markers of iron metabolism were not different between groups, except for ferritin. Studies addressing the long-term effects of higher hepcidin levels and their impact on subclinical anemia and iron status are warranted. a p < 0.05; b p < 0.01, c p < 0.001 dp < 0.0001.
RESUMO
Resumen: Introducción: la hipovitaminosis D se encuentra ampliamente extendida a nivel mundial, con consecuencias clínicas a nivel óseo y extraóseo. Entre los factores que la causan se encuentran los antiepilépticos (AE). En Uruguay no se conoce su prevalencia en niños ni en pacientes que reciben AE. Objetivos: conocer la prevalencia de hipovitaminosis D de niños y adultos en un prestador de salud y compararla con la prevalencia en pacientes bajo tratamiento con AE. Método: estudio descriptivo, transversal, realizado entre marzo y diciembre de 2017. Las variables analizadas fueron: niveles de vitamina D, calcio, fósforo, fosfatasa alcalina y parathormona intacta. Se consideró insuficiencia de vitamina D niveles menores de 30 ng/ml y déficit niveles menores de 20 ng/ml. Resultados: se incluyeron 113 pacientes, 60 niños y 53 adultos. La prevalencia global de insuficiencia de vitamina D fue de 89% y déficit de 60%. En niños expuestos a AE, la media de vitamina D fue 17,5 ng/ml, y en niños no expuestos 19,6 ng/ml. En adultos la media de vitamina D fue de 18,1 en expuestos a AE y 16,9 en no expuestos. La diferencia de medias no fue estadísticamente significativa en niños ni en adultos. Se observaron niveles de calcemia significativamente descendidos en niños y adultos con AE. Conclusiones: la insuficiencia de vitamina D fue cercana a 90% y el déficit superó el 50%. No se encontraron diferencias significativas entre grupos en hipovitaminosis D, pero se observaron niveles de calcemia reducidos en los expuestos a AE. Es necesario continuar analizando los factores que la causan y sus consecuencias clínicas.
Summary: Introduction: hypovitaminosis D is a highly spread condition worldwide, with clinical consequences that affect bone directly, among other manifestations. Antiepileptic drugs are among factors that cause this deficiency. In Uruguay, there is no information about hypovitaminosis D in children or patients who receive antiepileptic drugs. Objectives: to learn about the prevalence of hypovitaminosis D in children and adults in a health institution and to compare it with the prevalence in patients receiving antiepileptic drugs. Method: descriptive, transversal study conducted from March through December, 2017. The following variables were analysed: vitamin D, calcium, phosphorous, alkaline phosphatase and intact parathyroid hormone. Vitamin D insufficiency was defined as vitamin D levels of less than 30 ng per mL and deficiency as D levels of less than 20 ng per mL. Results: 113 patients were included in the study, 60 of which were children and 53 adults. Global prevalence of vitamin D insufficiency was 89% and deficiency was 60%. In children taking antiepileptic drugs, the average vitamin D value was 17.5 ng/ml and it was 19.6 ng/ml for those not exposed to those drugs. In adults, the average vitamin D value was 18.1 in the population taking antiepileptic drugs and 16.9 in patients not taking that medication. The difference between average values was not statistically significant in children or adults. Calcemia levels observed were significantly lower in both children and adults taking antiepileptic drugs. Conclusions: vitamin D insufficiency was close to 90% and deficiency was over 50%. No significant differences were found between hypovitaminosis D groups, although reduced calcemia was observed in patients exposed to antiepileptic drugs. Further studies are necessary to analyse factors that cause this condition and its clinical consequences.
Resumo: Introdução: a hipovitaminose D está amplamente difundida em todo o mundo, com consequências clínicas a nível ósseo e extraósseo. Entre os fatores que a causam estão os medicamentos antiepilépticos (AE). No Uruguai, sua prevalência em crianças ou em pacientes adultos recebendo AE não é conhecida. Objetivos: conhecer a prevalência de hipovitaminose D em crianças e adultos em um prestador de serviços de saúde e compará-la com a prevalência em pacientes em tratamento com AE. Método: estudo transversal descritivo realizado entre março e dezembro de 2017. As variáveis analisadas foram: níveis de vitamina D, cálcio, fósforo, fosfatase alcalina e paratormona intacta. Níveis menores que 30 ng / ml e níveis de déficit menores que 20 ng / ml foram considerados como insuficiência de vitamina D. Resultados: foram incluídos 113 pacientes, 60 crianças e 53 adultos. A prevalência global de insuficiência de vitamina D foi de 89% e déficit de 60%. Em crianças expostas à AE, a média de vitamina D foi de 17,5 ng / ml e em crianças não expostas de 19,6 ng / ml. Em adultos, a média de vitamina D foi de 18,1 nos expostos ao AE e de 16,9 nos não expostos. A diferença nas médias não foi estatisticamente significativa nas crianças nem nos adultos. Níveis de cálcio significativamente diminuídos foram observados em crianças e adultos com EA. Conclusões: a insuficiência de vitamina D foi próxima a 90% e o déficit ultrapassou 50%. Não foram encontradas diferenças significativas entre os grupos na hipovitaminose D, mas níveis reduzidos de cálcio foram observados naqueles expostos a EA. É necessário continuar analisando os fatores que o causam e suas consequências clínicas.
Assuntos
Deficiência de Vitamina D , Hipocalcemia , Anticonvulsivantes/efeitos adversosRESUMO
Recent work has shown that high-density lipoprotein (HDL) isolated from human atherosclerotic lesions and the blood of patients with established coronary artery disease contains elevated levels of 3-nitrotyrosine and 3-chlorotyrosine. A higher nitrotyrosine content in lipoprotein is significantly associated with diminished cholesterol efflux capacity of the lipoprotein. Since accelerated atherogenesis is a key complication of diabetes mellitus, and nitrosative stress has recently been implicated in diabetic pathology, we set out to demonstrate an increase in the circulating levels of nitrated apolipoprotein A (apoA)-I in type 2 diabetic patients and its putative correlation with metabolic biomarkers. In this work we addressed this hypothesis in a case-control study with 30 type 2 diabetic patients and 30 age-matched control subjects. Nitrated apoA-I was 3280+/-1910 absorbance peak area/apoA-I (g/L) for diabetic patients and 2320+/-890 for control subjects (p<0.037). This represents a 50% increase in circulating nitrated apoA-I in diabetic patients to age-matched controls. Diabetic patients also showed increases of a similar magnitude in circulating advanced glycation endproducts measured as pentosidine fluorescence (44.16+/-16.26 vs. 30.84+/-12.86 AU; p<0.01) and in circulating lipoperoxides (46.0+/-18.0 vs. 37.2+/-18.0 nmol/L; p<0.03). No significant correlation was found between nitration of apoA-I and glycosylated hemoglobin or any of the other parameters measured. If proven in subsequent functional and in vivo studies, increased nitrated apoA-I would represent another mechanism by which nitrosative stress participates in diabetic macro-angiopathy.