Prevalencia de disfunción tiroidea en la población española. Implicación del hierro en la fisiología tiroidea.

INTRODUCCIÓN La disfunción tiroidea es una patología frecuente en la población general. En España se dispone de pocos datos, de regiones pequeñas y de áreas con distinto estado nutricional de yodo, por lo que es necesario un estudio poblacional amplio y representativo de todo el país. La deficiencia de hierro es una de las más graves e importantes deficiencias nutricionales en el mundo. Estudios recientes relacionan la ferropenia con un metabolismo alterado de las hormonas tiroideas. Basándonos en la evidencia previa, nuestro objetivo es estudiar la asociación entre ferropenia y la disfunción tiroidea en una población libre de enfermedad tiroidea, representativa de la población general adulta en España. MATERIAL Y MÉTODOS El estudio [email protected] es una encuesta poblacional nacional, transversal, realizada entre los años 2008-2010. Se realizó un muestreo por conglomerados. De los más de 10.000 adultos elegibles, un 55,8% asistió a examen, 9,9% fueron excluidos (institucionalizados, enfermedad grave, gestación o parto reciente), dando una muestra final de 5061 individuos entre 18 y 93 años (41.6% hombres, 58,4% mujeres). El estudio fue aprobado por varios comités de ética y se obtuvo consentimiento informado de todos los participantes. Para el análisis de la ferropenia la muestra se centró en 3922 individuos (54,3% mujeres 45,7% hombres), libres de enfermedad tiroidea y con niveles de Anti-TPO < 50 IU/ml. Los participantes fueron evaluados en una única visita. Se obtuvo información de variables sociodemográficas y clínicas, así como exploración física y obtención de muestras biológicas de sangre y orina. Las muestras fueron gestionadas por el Biobanco del Hospital Regional Universitario de Málaga-IBIMA. Análisis estadístico Se calculó la prevalencia y el intervalo de confianza al 95% (IC 95%) de los diferentes subtipos de disfunción tiroidea en la muestra general y por sexo. Los datos se ajustaron a la estructura de la población española por edad y sexo. Para evaluar la asociación entre la disfunción tiroidea y otros factores, así como la relación entre ferropenia e hipotiroxinemia/hipotriyodotironinemia, usamos un modelo de regresión logística multivariante. Los valores aportados de p están basados en test de dos colas con significación estadística de 0,05. RESULTADOS La prevalencia de disfunción tiroidea sumando tanto hiper como hipotiroidismo fue de 9,9%, frente al 90,1% que no padecía ningún tipo de disfunción. Separando por tipos de patología tiroidea, el hipotiroidismo total supone el 9,1% (IC95% 8,2-10). El hipotiroidismo tratado representa el 4,2% (IC 95%: 3,6-4,9) de la población. El hipotiroidismo subclínico no tratado representa el 4,6% (IC 95%: 4.0-5,2) El hipotiroidismo clínico no tratado representa el 0,3% (IC 95%: 0,1-0,5). El hipotiroidismo total supone el 9,1% de la población española. El hipertiroidismo total supone el 0,8% de población (IC 95%: 0,6-1,1). En mujeres la prevalencia total fue de 14,4% y de 5,3% en hombres. Se encontraron anticuerpos anti-TPO en el 7,5% (IC 95%: 6,7-8,3) de la población española. En mujeres la prevalencia de anti-TPO es de 10,8% y en hombres es de 4,1%. La prevalencia de hipotiroxinemia aislada tomando como valor de referencia el p2,5 de la población es de 1,6% (IC95%: 1,0-2,2) en hombres y 2,4% (IC95%: 1,8-3,0) en mujeres. La prevalencia total es de 2,0% (IC95% 1,6-2,4). Tomando como valor de referencia el p5, es de 3,2% (IC95%: 2,4-4,0) en hombres y 4,9% (IC95%: 4,1-5,7) en mujeres. La prevalencia total es de 4,1% (IC95% 3,5-4,7). Las mujeres fueron 2.5 veces más propensas a tener hipotiroidismo de cualquier clase, que los hombres (p < 0.001), mientras que no hubo una asociación significativa de disfunción tiroidea con la edad. Los anti-TPO se asociaron se manera significativa con hipotiroidismo e hipertiroidismo. También había una asociación positiva entre la yoduria y la disfunción tiroidea. Se halló una asociación entre el hipotiroidismo y la zona de residencia (mayor probabilidad de hipotiroidismo en el centro de España comparado con la costa). Según las concentraciones de ferritina el 13,6% de la población tenía niveles de ferritina < 15 μg/L y el 14.7% tenía niveles de ferritina entre 15-29 μg/L. En el modelo de regresión logística multivariante, los sujetos con déficit de hierro (ferritina <30 μg/l) mostraron una mayor probabilidad de presentar hipotiroxinemia que la categoría de referencia (ferritina≥30), tanto aplicando criterios para T4L inferiores a p2.5 (OR 1.8 [IC95% 1.1-2.9] p<0.021) como aplicando criterios de T4L inferiores a p5 (OR 1.6 [IC95% 1.1-2.3] p=0,007). Asimismo, los sujetos con ferritina<30 μg/l mostraron una mayor probabilidad de presentar niveles descendidos de T3L, tanto aplicando criterios de T3L inferiores a 2.5 (OR 2.0 [IC95% 1.2-3.3] p=0,005) como para niveles por debajo de p5 (OR 1.8 [IC95% 1,3-2,6] p=0,001. No se encontró asociación entre los niveles de ferritina y presentar niveles de TSH por encima p97,5 (OR 0.9 [IC95% 0.5-1.4] p=0,557) ni por encima del p95 (OR 1,1 [IC95% 0,8-1,5] p=0,672. DISCUSIÓN Los resultados de este estudio de prevalencia nacional en España muestran que una gran proporción de la población adulta de nuestro país (aproximadamente 10%) padece una disfunción tiroidea. Dicha prevalencia viene dada en mayor medida por el hipotiroidismo tratado (4.2%) y las formas subclínicas (4,6%) de hipotiroidismo, mientras que el hipotiroidismo sin tratamiento clínico (0.3%) e hipertiroidismo (0,8%) eran mucho más infrecuentes. Hubo un claro predominio de la disfunción tiroidea en mujeres especialmente para el hipotiroidismo. Nuestro estudio muestra que la ferropenia se asocia a hipotiroxinemia e hipotriyodotironinemia en una cohorte libre de enfermedad tiroidea representativa de la población española, sin que haya modificaciones en los niveles de TSH. Dicho descenso se hace significativo a partir del nivel de ferritina sérica de 30 µg/l. La ferropenia puede alterar la síntesis de hormonas tiroideas por múltiples mecanismos: reducir la conversión periférica de T4 a T3, producir un aumento de la desyodación de T4 y T3 hacia rT3, reducir la actividad de la hemoproteína tiroperoxidasa, existiendo además un mecanismo hipotalámico-hipofisario que reduciría la secreción de TRH. Nuestros resultados están basados en asociaciones transversales, por lo que no podemos inferir mecanismos causales. Se necesitan estudios prospectivos y ensayos clínicos para ampliar el conocimiento en este campo

Usefulness of Muscle Ultrasonography in the Nutritional Assessment of Adult Patients with Cystic Fibrosis

Muscle ultrasonography of the quadriceps rectus femoris (QRF) is a technique on the rise in the assessment of muscle mass in application of nutritional assessment. The aim of the present study is to assess the usefulness of muscle ultrasonography in patients with cystic fibrosis, comparing the results with other body composition techniques such as anthropometry, bioelectrical impedance analysis (BIA), dual-energy X-ray absorptiometry (DXA), and handgrip strength (HGS). At the same time, we intend to assess the possible association with the nutritional and respiratory status. Methods: This was a prospective observational study in adult patients with cystic fibrosis in a clinically stable situation. Muscle ultrasonography of the QRF was performed, and the results were compared with other measures of body composition: anthropometry, BIA, and DXA. HGS was used to assess muscle function. Respiratory parameters were collected, and nutritional status was assessed using Global Leadership Initiative on Malnutrition (GLIM) criteria. Results: A total of 48 patients were included, with a mean age of 34.1 ± 8.8 years. In total, 24 patients were men, and 24 patients were women. Mean BMI was 22.5 ± 3.8 kg/m2. Mean muscular area rectus anterior (MARA) was 4.09 ± 1.5 cm2, and mean muscular circumference rectus was 8.86 ± 1.61 cm. A positive correlation was observed between the MARA and fat-free mass index (FFMI) determined by anthropometry (r = 0.747; p < 0.001), BIA (r = 0.780; p < 0.001), and DXA (r = 0.678; p < 0.001), as well as muscle function (HGS: r = 0.790; p < 0.001) and respiratory parameters (FEV1; r = 0.445, p = 0.005; FVC: r = 0.376, p = 0.02; FEV1/FVC: r = 0.344, p = 0.037). A total of 25 patients (52.1%) were diagnosed with malnutrition according to GLIM criteria. Differences were observed when comparing the MARA based on the diagnosis of malnutrition (4.75 ± 1.65 cm2 in normo-nourished vs. 3.37 ± 1.04 in malnourished; p = 0.014). (...)This study was partially funded by an unrestricted grant from Vegenat Laboratories (Spain) and the Fundación SEEN-Nutricia 2021 Grant for the assessment of body composition by ultrasound. Partial funding for open access charge: Universidad de Málag

Serum vascular endothelial growth factor b and metabolic syndrome incidence in the population based cohort [email protected] study

Background/Objectives Although vascular endothelial growth factor b (VEGFb) might have an impact on the development of obesity, diabetes and related disorders, the possible relationship between VEGFb serum levels and the incidence of these metabolic complications in humans is still unknown. The aim of our study was to evaluate the association between VEGFb serum levels and the new-onset of metabolic syndrome (MS) and its components in the Spanish adult population after 7.5 years of follow-up. Subjects/Methods A total of 908 subjects from the [email protected] cohort study without MS at cross-sectional stage according to International Diabetes Federation (IDF) or Adult Treatment Panel III (ATP-III) criteria were included. Additionally, five sub-populations were grouped according to the absence of each MS component at baseline. Socio-demographic, anthropometric and clinical data were recorded. The Short Form of International Physical Activity Questionnaire (SF-IPAQ) was used to estimate physical activity. A fasting blood extraction and an oral glucose tolerance test were performed. Serum determinations of glucose, lipids, hsCRP and insulin were made. VEGFb levels were determined and categorized according to the 75th percentile of the variable. New cases of MS and its components were defined according to ATPIII and IDF criteria. Results A total of 181 or 146 people developed MS defined by IDF or ATP-III criteria respectively. Serum triglyceride levels, hs-CRP and systolic blood pressure at the baseline study were significantly different according to the VEGFb categories. Adjusted logistic regression analysis showed that the likelihood of developing MS and abdominal obesity was statistically reduced in subjects included in the higher VEGFb category. Conclusion Low serum levels of VEGFb may be considered as early indicators of incident MS and abdominal obesity in the Spanish adult population free of MS, independently of other important predictor variables.This investigation has been supported by CIBERDEM (Ministerio de Economia, Industria y Competitividad-ISCIII), Ministerio de Sanidad, Servicios Sociales e IgualdadISCIII, Instituto de Salud Carlos III (research grants PI20/01322, PI18/01165, PI17/02136, PI14/00710) and cofunding by the European Regional Development Fund (ERDF) "A way to build Europe". LifeScan Espana (Madrid, Spain) kindly donated the glucometers and test strips for capillary glucose measurements. Cristina MaldonadoAraque is a researcher in the `Rio Hortega' program (CM19/00186) financed by the Instituto de Salud Carlos III. Natalia Colomo is a member of the regional "Accion B para clinicos investigadores" research program of the Consejeria de Salud of the Junta de Andalucia, Spain (B-0002-17). Gemma Rojo-Martinez belongs to the Nicolas Monardes research program of the Consejeria de Salud (C-0060-2012; Junta de Andalucia, Spain)

Association between long term exposure to particulate matter and incident hypertension in Spain

Exposure to air particulate matter has been linked with hypertension and blood pressure levels. The metabolic risks of air pollution could vary according to the specific characteristics of each area, and has not been sufficiently evaluated in Spain. We analyzed 1103 individuals, participants in a Spanish nationwide population based cohort study ([email protected]), who were free of hypertension at baseline (2008-2010) and completed a follow-up exam of the cohort (2016-2017). Cohort participants were assigned air pollution concentrations for particulate matter < 10 mu m (PM10) and < 2.5 mu m (PM2.5) during follow-up (2008-2016) obtained through modeling combined with measurements taken at air quality stations (CHIMERE chemistry-transport model). Mean and SD concentrations of PM10 and PM2.5 were 20.17 +/- 3.91 mu g/m(3) and 10.83 +/- 2.08 mu g/m(3) respectively. During follow-up 282 cases of incident hypertension were recorded. In the fully adjusted model, compared with the lowest quartile of PM10, the multivariate weighted ORs (95% CIs) for developing hypertension with increasing PM10 exposures were 0.82 (0.59-1.14), 1.28 (0.93-1.78) and 1.45 (1.05-2.01) in quartile 2, 3 and 4 respectively (p for a trend of 0.003). The corresponding weighted ORs according to PM2.5 exposures were 0.80 (0.57-1.13), 1.11 (0.80-1.53) and 1.48 (1.09-2.00) (p for trend 0.004). For each 5-mu g/m(3) increment in PM10 and PM2.5 concentrations, the odds for incident hypertension increased 1.22 (1.06-1.41) p = 0.007 and 1.39 (1.07-1.81) p = 0.02 respectively. In conclusion, our study contributes to assessing the impact of particulate pollution on the incidence of hypertension in Spain, reinforcing the need for improving air quality as much as possible in order to decrease the risk of cardiometabolic disease in the population

Association between exposure to air pollution and blood lipids in the general population of Spain.

Background and Aims: We aimed to assess the associations of exposure to air pollutants and standard and advanced lipoprotein measures, in a nationwide sample representative of the adult population of Spain.Methods: We included 4647 adults (>18 years), participants in the national, cross- sectional, population- based [email protected] study, conducted in 2008– 2010. Standard lipid measurements were analysed on an Architect C8000 Analyzer (Abbott Laboratories SA). Lipoprotein analysis was made by an advanced 1H- NMR lipoprotein test (Liposcale®). Participants were assigned air pollution con-centrations for particulate matter <10 μm (PM10), <2.5 μm (PM2.5) and nitrogen dioxide (NO2), corresponding to the health examination year, obtained by mod-elling combined with measurements taken at air quality stations (CHIMERE chemistry- transport model).Results: In multivariate linear regression models, each IQR increase in PM10, PM2.5 and NO2 was associated with 3.3%, 3.3% and 3% lower levels of HDL- c and 1.3%, 1.4% and 1.1% lower HDL particle (HDL- p) concentrations (p< .001 for all associations). In multivariate logistic regression, there was a significant associa-tion between PM10, PM2.5 and NO2 concentrations and the odds of presenting low HDL- c (<40 mg/dL), low HDL- p (<p25) and higher LDL particle (LDL- p) concentrations (≥p75). In subgroup analyses there were stronger associations be-tween PM10 and NO2 and low HDL- p in men (p for interaction .008 and .034), and between NO2 and low HDL- p in individuals with obesity (p for interaction .015).Conclusions: Our study shows an association between the exposure to air pol-lutants and blood lipids in the general population of Spain, suggesting a link to atherosclerosisFunding for open access charge: Universidad de Málaga / CBU

Ambient air pollution and thyroid function in Spanish adults. A nationwide population-based study ([email protected] study)

Background Recent reports have suggested that air pollution may impact thyroid function, although the evidence is still scarce and inconclusive. In this study we evaluated the association of exposure to air pollutants to thyroid function parameters in a nationwide sample representative of the adult population of Spain. Methods The [email protected] study is a national, cross-sectional, population-based survey which was conducted in 2008-2010 using a random cluster sampling of the Spanish population. The present analyses included 3859 individuals, without a previous thyroid disease diagnosis, and with negative thyroid peroxidase antibodies (TPO Abs) and thyroid-stimulating hormone (TSH) levels of 0.1-20 mIU/L. Participants were assigned air pollution concentrations for particulate matter <2.5 mu m (PM2.5) and Nitrogen Dioxide (NO2), corresponding to the health examination year, obtained by means of modeling combined with measurements taken at air quality stations (CHIMERE chemistry-transport model). TSH, free thyroxine (FT4), free triiodothyronine (FT3) and TPO Abs concentrations were analyzed using an electrochemiluminescence immunoassay (Modular Analytics E170 Roche). Results In multivariate linear regression models, there was a highly significant negative correlation between PM2.5 concentrations and both FT4 (p<0.001), and FT3 levels (p<0.001). In multivariate logistic regression, there was a significant association between PM2.5 concentrations and the odds of presenting high TSH [OR 1.24 (1.01-1.52) p=0.043], lower FT4 [OR 1.25 (1.02-1.54) p=0.032] and low FT3 levels [1.48 (1.19-1.84) p=<0.001] per each IQR increase in PM2.5 (4.86 mu g/m(3)). There was no association between NO2 concentrations and thyroid hormone levels. No significant heterogeneity was seen in the results between groups of men, pre-menopausal and post-menopausal women. Conclusions Exposures to PM2.5 in the general population were associated with mild alterations in thyroid function.CIBERDEM (Ministerio de Economia, Industria y Competitividad-ISCIII), Ministerio de Sanidad, Servicios Sociales e Igualdad-ISCIII, Instituto de Salud Carlos III (PI17/02136, PI20/01322), Consejeria de Salud y familias (PI-0144-2018), European Regional Development Fund (ERDF) "A way to build Europe". GRM belongs to the regional Nicolas Monardes research program of the Consejeria de Salud (RC-0006-2016; Junta de Andalucia, Spain). CMA is recipient of a "Rio Hortega" research contract (CM19/00186, Instituto de Salud Carlos III). VKDG is recipient of a "Rio Hortega" research contract (CM21/00214, Instituto de Salud Carlos III)

Fatty liver index as a predictor for type 2 diabetes in subjects with normoglycemia in a nationwide cohort study

Our aim was to evaluate whether fatty liver index (FLI) is associated with the risk of type 2 diabetes (T2DM) development within the Spanish adult population and according to their prediabetes status; additionally, to examine its incremental predictive value regarding traditional risk factors. A total of 2260 subjects (Prediabetes: 641 subjects, normoglycemia: 1619 subjects) from the [email protected] cohort study were studied. Socio-demographic, anthropometric, clinical data and survey on habits were recorded. An oral glucose tolerance test was performed and fasting determinations of glucose, lipids and insulin were made. FLI was calculated and classified into three categories: Low ( 60). In total, 143 people developed diabetes at follow-up. The presence of a high FLI category was in all cases a significant independent risk factor for the development of diabetes. The inclusion of FLI categories in prediction models based on different conventional T2DM risk factors significantly increase the prediction power of the models when all the population was considered. According to our results, FLI might be considered an early indicator of T2DM development even under normoglycemic condition. The data also suggest that FLI could provide additional information for the prediction of T2DM in models based on conventional risk factors

Thyroid hormone resistance index and mortality in euthyroid subjects: [email protected] study.

It has been proposed that a mild form of acquired resistance to thyroid hormone may occur in the general population. Its clinical significance remains largely unknown. The objective of the study was to explore whether a newly described thyroid hormone resistance index is associated with the risk of mortality in a sample of community-dwelling euthyroid subjects representative of the adult population of Spain. Longitudinal observational study including 3750 individuals, free of thyroid disease, TPO antibodies-negative ( We used the Thyroid Feedback Quantile-based Index (TFQI) as a marker of resistance to thyroid hormone. The study population was grouped into categories according to their TFQI values at baseline. Fatal events were ascertained from the national death registry (end of follow-up December 2016). A total of 231 deaths were recorded during an average follow-up of 7.3 years. Compared with the category with the highest sensitivity to free thyroxine (TFQI ≤ p5) (reference), the relative risk of mortality in the categories with TFQI > p5 and ≤p25; >p25 and ≤p50; >p50 and ≤p75; >p75 and ≤p95 and >p95 were 1.01, (0.47-2.19), 1.42 (0.68-2.97), 1.54 (0.74-3.22), 1.47 (0.70-3.11) and 2.61 (1.16-5.89), respectively (P for trend 0.003). The association remained significant after multivariate adjustment of the data (P for trend 0.017). A thyroid hormone resistance index focused on deviations of the average pituitary response to thyroid hormones may be associated with all-cause mortality independently of other conventional risk factors and comorbidities

Iodine deficiency and mortality in spanish adults: [email protected] study

Background: Longitudinal data assessing the impact of iodine deficiency (ID) on mortality are scarce. We aimed to study the association between the state of iodine nutrition and the risk of total and cause-specific mortality in a representative sample of the Spanish adult population. Methods: We performed a longitudinal observational study to estimate mortality risk according to urinary iodine (UI) concentrations using a sample of 4370 subjects >18 years representative of the Spanish adult population participating in the nationwide study [email protected] (2008-2010). We used Cox regression to assess the association between UI at the start of the study (<50, 50-99, 100-199, 200-299, and ≥300 μg/L) and mortality during follow-up (National death registry-end of follow-up December 2016) in raw models, and adjusted for possible confounding variables: age, sex, educational level, hypertension, diabetes, obesity, chronic kidney disease, smoking, hypercholesterolemia, thyroid dysfunction, diagnosis of cardiovascular disease or cancer, area of residence, physical activity, adherence to Mediterranean diet, dairy and iodinated salt intake. Results: A total of 254 deaths were recorded during an average follow-up period of 7.3 years. The causes of death were cardiovascular 71 (28%); cancer 85 (33.5%); and other causes 98 (38.5%). Compared with the reference category with adequate iodine nutrition (UI 100-300 μg/L), the hazard ratios (HRs) of all-cause mortality in the category with UI ≥300 μg/L were 1.04 (95% confidence interval [CI 0.54-1.98]); however, in the categories with 50-99 UI and <50 μg/L, the HRs were 1.29 [CI 0.97-1.70] and 1.71 [1.18-2.48], respectively (p for trend 0.004). Multivariate adjustment did not significantly modify the results. Conclusions: Our data indicate an excess mortality in individuals with moderate-severe ID adjusted for other possible confounding factors