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Understanding the effects of climate change is one of the most challenging goals for biodiversity conservation. The forests of Andalusia, in Southern Spain, are part of an important Mediterranean Basin biodiversity hotspot. However, great changes in climate are expected to occur in this region, and there is an increasing need to assess the vulnerability of its vegetation. We assess the vulnerability of twelve forest types in the region that are included in the European Directive 92/43/EEC as Habitats of Community Interest (HCI). HCI are natural habitat types which are in danger, have a small natural range, or present an outstanding example of a biogeographical regions in the European Union. We assessed vulnerability by analyzing the climate exposure level of each forest type under two global climate models (MRI-CGCM3, which predicts warmer and wetter conditions, and MIROC-ESM which predicts hotter and drier conditions), two emission scenarios (RCP4.5, a representative concentration pathway that predicts stable emissions of CO 2 , and RCP8.5, that predicts the highest CO 2 emissions) by the mid- and end-century time periods. The vulnerability analysis also includes the sensitivity and adaptive capacity of the dominant tree species which compose each forest type. An overall vulnerability score was calculated for each forest type, model, scenario and time period. High-elevation forest types and those with high moisture requirements were more vulnerable to climate change, while forest types dominated by more thermophilic species were less vulnerable and more resilient. The worst climate impacts were predicted in the MIROC-ESM model and RCP8.5 scenario by the end of the century (2070-2100), while the least climatic stress was obtained in the MRI-CGCM3 model and RCP4.5 scenario by the mid-century (2040-2070), which still shows high potential stress for most forest types. By the end of the century, the climate exposure of the entire forest domain will range between 32 % in the least stressful situation (MRI-CGCM3 and RCP4.5), and 98 % in the most climatically stressful situation (MIROC-ESM and RCP8.5). However, the effects of climate change will be perceptible by the mid-century, with most of the HCI forest types suffering climate stress. The "Andalusian oak forest" and the "Corylus wet forest" types were the most vulnerable to climate change, while the "Mediterranean pine forest", the "Olea and Ceratonia forests" and the "oak forests" were the least vulnerable. This assessment identifies the vulnerable forest types to climate change in the south of the Iberian Peninsula, and provides context for natural resource managers in making decisions about how to adapt forests to the impacts of climate change., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

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 Di@bet.es 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 <2.5μm (PM 2.5 ) and Nitrogen Dioxide (NO 2 ), 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 PM 2.5 concentrations and both FT4 (p<0.001), and FT3 levels (p<0.001). In multivariate logistic regression, there was a significant association between PM 2.5 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 PM 2.5 (4.86 μg/m 3 ). There was no association between NO 2 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 PM 2.5 in the general population were associated with mild alterations in thyroid function., (© 2022. The Author(s).)

Festuca indigesta subsp. indigesta (Poaceae) is endemic to the southeast of Spain, and until recently, it was considered that its range of distribution was restricted to the siliceous core of Sierra Nevada. However, it has been recently extended in the territory to others calcareous mountains. This study investigates the cytogenetic variability throughout the geographic range of this taxon, the possible edaphic preferences of each cytotype, and the morphological variation of cytotypes. Genome sizes and ploidy levels were estimated using flow cytometry and chromosome count. Soil samples were collected to test the nature of the substrate, i.e., pH, and calcium and magnesium contents. Finally, morphological characters were measured in herbarium specimens. This study provides the first genome size data for the species. Hidden cytogenetic diversity was detected in the taxon, comprising hexaploid (2n = 6 x = 42), octoploid (2n = 8 x = 56) and dodecaploid (2n = 12 x = 84) individuals. No relationship between substrate nature and cytotype was observed. Morphological differences were detected for the size of floral parts and stomata among cytotypes, but these were blurred if the entire morphological variation range was considered. Our results suggest that each mountain range could act as a reservoir of morphologically cryptic genetic diversity regarding this taxon.

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 (di@bet.es), 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 μm (PM 10 ) and < 2.5 μm (PM 2.5 ) 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 PM 10 and PM 2.5 were 20.17 ± 3.91 μg/m 3 and 10.83 ± 2.08 μg/m 3 respectively. During follow-up 282 cases of incident hypertension were recorded. In the fully adjusted model, compared with the lowest quartile of PM 10, the multivariate weighted ORs (95% CIs) for developing hypertension with increasing PM 10 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 PM 2.5 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-μg/m 3 increment in PM 10 and PM 2.5 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., (© 2021. The Author(s).)

Background: Identifying those parameters that could potentially predict the deterioration of metabolically healthy phenotype is a matter of debate. In this field, epigenetics, in particular DNA methylation deserves special attention., Results: The aim of the present study was to analyze the long-term evolution of methylation patterns in a subset of metabolically healthy subjects in order to search for epigenetic markers that could predict the progression to an unhealthy state. Twenty-six CpG sites were significantly differentially methylated, both at baseline and 11-year follow-up. These sites were related to 19 genes or pseudogenes; a more in-depth analysis of the methylation sites of these genes showed that CYP2E1 had 50% of the collected CpG sites differently methylated between stable metabolically healthy obesity (MHO) and unstable MHO, followed by HLA-DRB1 (33%), ZBTB45 (16%), HOOK3 (14%), PLCZ1 (14%), SLC1A1 (12%), MUC2 (12%), ZFPM2 (12.5%) and HLA-DQB2 (8%). Pathway analysis of the selected 26 CpG sites showed enrichment in pathways linked to th1 and th2 activation, antigen presentation, allograft rejection signals and metabolic processes. Higher methylation levels in the cg20707527 ( ZFPM2 ) could have a protective effect against the progression to unstable MHO (OR: 0.21, 95%CI (0.067-0.667), p < 0.0001), whilst higher methylation levels in cg11445109 ( CYP2E1 ) would increase the progression to MUO; OR: 2.72, 95%CI (1.094-6.796), p < 0.0014; respectively)., Conclusions: DNA methylation status is associated with the stability/worsening of MHO phenotype. Two potential biomarkers of the transition to an unhealthy state were identified and deserve further investigation (cg20707527 and cg11445109). Moreover, the described differences in methylation could alter immune system-related pathways, highlighting these pathways as therapeutic targets to prevent metabolic deterioration in MHO patients.

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 Di@bet.es 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 (< 30), intermediate (30-60) and high (> 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., (© 2021. The Author(s).)

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 Di@bet.es (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.

Introduction: Metabolic syndrome (MetS) is an important predictor of cardiovascular mortality. Identification of occurrence and regression trends of MetS could permit elaboration of preventive strategies with new targets. The objective of this study was to analyze the occurrence and regression rates of MetS and its associated factors in the representative cohort of Spain of the di@bet.es study., Research Design and Methods: The di@bet.es study is a prospective cohort where 5072 people representative of the Spanish population over 18 years of age were randomly selected between 2009 and 2010. Follow-up was a median of 7.5 (IQR 7.2-7.9) years, with 2408 (47%) participating subjects. A total of 1881 (78%) subjects had all the pertinent data available and were included in this study., Results: Of the 1146 subjects without baseline criteria for MetS, 294 (25.7%) developed MetS during follow-up, while of the 735 patients with prior MetS, 148 (20.1%) presented regression. Adjusted MetS incidence per 1000 person-years was 38 (95% CI 32 to 44), while regression incidence was 36 (95% CI 31 to 41). Regression rate was independently higher than incidence rate in the following: women, subjects aged 18-45, university-degree holders, patients without central obesity, without hypertension, as well as those with body mass index of <25 kg/m 2 . Lower progression and higher regression rates were observed with an adapted 14-point Mediterranean Diet adherence screener questionnaire score of >11 in both groups and with >500 and>2000 MET-min/week of physical activity, respectively., Conclusions: This study provides MetS incidence and regression rates, and identifies the target population for intervention strategies in Spain and possibly in other countries., Competing Interests: Competing interests: EMo has been on advisory boards, has received consulting fees, speaker honoraria or research support from Astra Zeneca, Menarini Laboratories, Merck Sharp & Dohme, Novartis, NovoNordisk and Sanofi., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Our aim was to determine the incidence of type 2 diabetes mellitus in a nation-wide population based cohort from Spain (di@bet.es study). The target was the Spanish population. In total 5072 people older than 18 years,were randomly selected from all over Spain). Socio-demographic and clinical data, survey on habits (physical activity and food consumption) and weight, height, waist, hip and blood pressure were recorder. A fasting blood draw and an oral glucose tolerance test were performed. Determinations of serum glucose were made. In the follow-up the same variables were collected and HbA1c was determined. A total of 2408 subjects participated in the follow-up. In total, 154 people developed diabetes (6.4% cumulative incidence in 7.5 years of follow-up). The incidence of diabetes adjusted for the structure of age and sex of the Spanish population was 11.6 cases/1000 person-years (IC95% = 11.1-12.1). The incidence of known diabetes was 3.7 cases/1000 person-years (IC95% = 2.8-4.6). The main risk factors for developing diabetes were the presence of prediabetes in cross-sectional study, age, male sex, obesity, central obesity, increase in weight, and family history of diabetes. This work provides data about population-based incidence rates of diabetes and associated risk factors in a nation-wide cohort of Spanish population.

Objective The activity of brown adipose tissue is sensitive to changes in ambient temperature. A lower exposure to cold could result in an increased risk of developing diabetes at population level, although this factor has not yet been sufficiently studied. Design We studied 5072 subjects, participants in a national, cross-sectional population-based study representative of the Spanish adult population (Di@bet.es study). All subjects underwent a clinical, demographic and lifestyle survey, a physical examination and blood sampling (75 g oral glucose tolerance test). Insulin resistance was estimated with the homeostasis model assessment (HOMA-IR). The mean annual temperature (°C) in each individual municipality was collected from the Spanish National Meteorology Agency. Results Linear regression analysis showed a significant positive association between mean annual temperature and fasting plasma glucose (β: 0.087, P < 0.001), 2 h plasma glucose (β: 0.049, P = 0.008) and HOMA-IR (β: 0.046, P = 0.008) in multivariate adjusted models. Logistic regression analyses controlled by multiple socio-demographic variables, lifestyle, adiposity (BMI) and geographical elevation showed increasing odds ratios for prediabetes (WHO 1999), ORs 1, 1.26 (0.95-1.66), 1.08 (0.81-1.44) and 1.37 (1.01-1.85) P for trend = 0.086, diabetes (WHO 1999) ORs 1, 1.05 (0.79-1.39), 1.20 (0.91-1.59) and 1.39 (1.02-1.90) P = 0.037, and insulin resistance (HOMA-IR ≥75th percentile of the non-diabetic population): ORs 1, 1.03 (0.82-1.30), 1.22 (0.96-1.55), 1.26 (0.98-1.63) (P for trend = 0.046) as the mean annual temperature (into quartiles) rose. Conclusions Our study reports an association between ambient temperature and the prevalence of dysglycemia and insulin resistance in Spanish adults, consistent with the hypothesis that a lower exposure to cold could be associated with a higher risk of metabolic derangements.

To date it is not clear what the role of dairy products is in metabolic diseases like diabetes, obesity, and hypertension. Therefore, the aim of this study is to test the association between dairy product consumption and those pathologies. A cross-sectional study was conducted with 5081 adults included in the di@bet.es study, from 100 health centers around Spain. Food frequency questionnaires were carried out concerning consumption habits, which included dairy product consumption. Logistic regression models were used for the association analyses between the variables controlling confounding variables. Women had a higher consumption of milk, cheese, or yogurt than men ( p < 0.0001), but men consumed more sugar dairy products ( p < 0.001). People who live in the North of Spain consume more dairy products than those who live in the East. Dairy product consumption was inversely associated with the presence of hypertension regardless of age, sex, geographical region, and body mass index (BMI) (Odds Ratio (OR) 0.743; p = 0.022). The presence of obesity was inversely associated with dairy consumption regardless of age, sex, and geographical region (OR 0.61; p < 0.001). Milk consumption was not associated with diabetes. Our results show that consuming dairy products is associated with a better metabolic profile in the Spanish population.

Previous studies have suggested that iron deficiency (ID) may impair thyroid hormone metabolism, however replication in wide samples of the general adult population has not been performed. We studied 3846 individuals free of thyroid disease, participants in a national, cross sectional, population based study representative of the Spanish adult population. Thyroid stimulating hormone (TSH), free thyroxin (FT4) and free triiodothyronine (FT3) were analyzed by electrochemiluminescence (E170, Roche Diagnostics). Serum ferritin was analyzed by immunochemiluminescence (Architect I2000, Abbott Laboratories). As ferritin levels decreased (>100, 30-100, 15-30, <15 µg/L) the adjusted mean concentrations of FT4 (p < 0.001) and FT3 (p < 0.001) descended, whereas TSH levels remained unchanged (p = 0.451). In multivariate logistic regression models adjusted for age, sex, UI, BMI and smoking status, subjects with ferritin levels <30 µg/L were more likely to present hypothyroxinemia (FT4 < 12.0 pmol/L p5): OR 1.5 [1.1-2.2] p = 0.024, and hypotriiodothyroninemia (FT3 < 3.9 pmol/L p5): OR 1.8 [1.3-2.6] p = 0.001 than the reference category with ferritin ≥30 µg/L. There was no significant heterogeneity of the results between men, pre-menopausal and post-menopausal women or according to the iodine nutrition status. Our results confirm an association between ID and hypothyroxinemia and hypotriiodothyroninemia in the general adult population without changes in TSH.

Background and Objectives: The objective of this study was to establish reference values for hand grip strength, compare the results obtained with Collin and Jamar type dynamometers and determine their association with anthropometric and lean mass measurements., Material and Methods: This cross-sectional population-based study was undertaken in Pizarra (Málaga, Spain). The grip strength of the dominant hand was measured using Collin and Jamar dynamometers. Skinfolds (triceps, abdominal, biceps of dominant arm and subscapular) were measured, and body composition was estimated. Eight hundred seventeen adults randomly selected from the census were recruited. Dynamometry reference values are presented for the dominant hand, by gender and age groups., Results: No determinations could be made with the Collin dynamometer in 69 women due to the difficulty in grasping the dynamometer. We found significant positive correlations between the measurements with Jamar and Collin dynamometers (r = 0.782; p < 0.001) and between grip strength and lean mass index (LMI), determined by both dynamometers (r = 0.538, p < 0.001 and r = 0.462, p < 0.001, respectively). Malnourished patients according to LMI had significantly lower grip strength than normally nourished patients (p < 0.001 for Jamar; p < 0.02 for Collin)., Conclusions: Dynamometry reference values in the Spanish population are presented. We recommend the use of the Jamar type dynamometer versus the Collin type dynamometer. Hand grip dynamometry is associated with lean mass, which confirms its usefulness in nutritional assessment.

The factors regulating TNF alpha (TNFa) levels could be considered therapeutic targets against metabolic syndrome development. DNA methylation is a potent regulator of gene expression and may be associated with protein levels. In this study we investigate whether the effect of dietary fatty acids on TNFa released from adipocytes might be associated with modifications of the TNFa promoter DNA methylation status. A group of rats was assigned to three diets with a different composition of saturated, monounsaturated and polyunsaturated fatty acids. Samples of visceral adipose tissues were taken for adipocyte isolation, in which released TNFa levels were measured, and for methylation and expression studies. In addition, 3 T3-L1 cells were treated with palmitic, oleic and linoleic acids, with and without 5-Azacitydine (5-AZA). After treatments, cells and supernatants were included in the same analyses as rat samples. TNFa promoter methylation levels, gene expression and secretion were different according to the diets and fatty acid treatments associated with them. Cells treated with 5-AZA displayed higher TNFa levels than in the absence of 5-AZA, without differences between fatty acids. According to our results, dietary fatty acid regulation of adipocyte TNFa levels may be mediated by epigenetic modifications of the TNFa promoter DNA methylation levels., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The satiating effects of cow dairy have been thoroughly investigated; however, the effects of goat dairy on appetite have not been reported so far. Our study investigates the satiating effect of two breakfasts based on goat or cow dairy and their association with appetite related hormones and metabolic profile. Healthy adults consumed two breakfasts based on goat (G-Breakfast) or cow (C-Breakfast) dairy products. Blood samples were taken and VAS tests were performed at different time points. Blood metabolites were measured and Combined Satiety Index (CSI) and areas under the curves (AUC) were calculated. Desire to eat rating was significantly lower (breakfast & time interaction p < 0.01) and hunger rating tended to be lower (breakfast & time interaction p = 0.06) after the G-breakfast. None of the blood parameters studied were different between breakfasts; however, AUC GLP-1 was inversely associated with the AUC hunger and AUC desire-to-eat after the G-Breakfast, whereas triglyceride levels were directly associated with AUC CSI after the C-Breakfast. Our results suggest a slightly higher satiating effect of goat dairy when compared to cow dairy products, and pointed to a potential association of GLP-1 and triglyceride levels with the mechanisms by which dairy products might affect satiety after the G-Breakfast and C-Breakfast, respectively., Competing Interests: The authors declare no conflict of interest and the founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Objective: To analyze the reference range of thyroid-stimulating hormone (TSH) in different BMI categories and its impact on the classification of hypothyroidism., Methods: The study included 3,928 individuals free of thyroid disease (without previous thyroid disease, no interfering medications, TSH <10 µUI/mL and thyroid peroxidase antibodies [TPO Abs] <50 IU/mL) who participated in a national, cross-sectional, population-based study and were representative of the adult population of Spain. Data gathered included clinical and demographic characteristics, physical examination, and blood and urine sampling. TSH, free thyroxine, free triiodothyronine, and TPO Ab were analyzed by electrochemiluminescence (E170, Roche Diagnostics, Basel, Switzerland)., Results: The reference range (p2.5-97.5) for TSH was estimated as 0.6 to 4.8 µUI/mL in the underweight category (BMI<20 kg/m 2 ), 0.6 to 5.5 µUI/mL in the normal-weight category (BMI 20-24.9 kg/m 2 ), 0.6 to 5.5 µUI/mL in the overweight category (BMI 25-29.9 kg/m 2 ), 0.5 to 5.9 µUI/mL in the obesity category (BMI 30-39.9 kg/m 2 ), and 0.7 to 7.5 µUI/mL in the morbid obesity category (BMI ≥40). By using the reference criteria for the normal-weight population, the prevalence of high TSH levels increased threefold in the morbid obesity category (P < 0.01)., Conclusions: Persons with morbid obesity might be inappropriately classified if the standard ranges of normality of TSH for the normal-weight population are applied to them., (© 2017 The Obesity Society.)

Purpose: We have investigated the epigenetic regulation by dietary fatty acids of Vegfb levels in rats' white adipose tissue and 3T3-L1 cells., Methods: A group of rats were assigned to three diets, each one with a different composition of saturated, monounsaturated and polyunsaturated fatty acids. Samples of white adipose tissues were taken for the methylation and expression studies. Additionally, 3T3-L1 cells were treated with palmitic, oleic, and linoleic fatty acids. After treatment, cells were harvested and genetic material was extracted for the analysis of Vegfb levels., Results: We report evidence of changes in the methylation levels of the CpG island at the Vegfb promoter and in the Vegfb expression levels in vivo and in vitro by dietary fatty acid, with the main contribution of the linoleic fatty acid. Vegfb promoter methylation levels were closely related to the Vegfb gene expression., Conclusion: According to our results, the regulation of Vegfb gene expression by dietary fatty acids may be mediated, at least in part, by epigenetic modifications on Vegfb promoter methylation. Considering the deep association between angiogenesis and tissue growth, we suggest the nutriepigenetic regulation of Vegfb as a key target in the control of the adipose tissue expansion.

Background: The aim of this study was to investigate the national prevalence of thyroid dysfunction in Spain and its association with various clinical, environmental, and demographic variables., Methods: The study included 4554 subjects (42.4% men) with a mean age of 50 years (range 18-93 years), who were participants in a national, cross-sectional, population-based survey conducted in 2009-2010. Data gathered included clinical and demographic characteristics, physical examination, and blood sampling. Thyrotropin, free thyroxine, free triiodothyronine, and thyroid peroxidase antibody (TPOAb) concentrations were analyzed by electrochemiluminescence. Urinary iodine (UI) levels were measured in an isolated urine sample., Results: The prevalence of treated hypothyroidism, untreated subclinical hypothyroidism, and untreated clinical hypothyroidism was 4.2% [confidence interval (CI) 3.6-4.9%], 4.6% [CI 4.0-5.2%], and 0.3% [CI 0.1-0.5%], respectively. The prevalence of total hypothyroidism (including all fractions) was 9.1% [CI 8.2-10.0%]. The prevalence of total hyperthyroidism was 0.8% [CI 0.6-1.1]. A total of 7.5% [CI 6.7-8.3%] of the population tested positive for TPOAbs (≥50 IU/mL). In multivariate logistic regression models, TPOAbs were strongly associated with both hypothyroidism (p < 0.001) and hyperthyroidism (p = 0.005), whereas high UI levels (>200 μg/g creatinine) were associated with hypothyroidism (p < 0.001). The positive association between UI and hypothyroidism remained for both treated (p < 0.001) and untreated (p < 0.05) hypothyroidism, whereas it was especially significant for non-autoimmune (TPOAbs negative) forms (p < 0.001). At UI levels ≥200 μg/g, there was a positive correlation between UI and thyrotropin levels (β = 0.152, p < 0.001) and a negative correlation between UI and free triiodothyronine levels (β = -0.134, p = 0.001)., Conclusion: According to the data, a large proportion (10%) of the Spanish population has some evidence of thyroid dysfunction. High TPOAb concentrations were associated with both hypo- and hyperthyroidism, whereas high UI concentrations were associated with hypothyroidism.

Desde hace algún tiempo sabemos que la talla de las poblaciones es un buen instrumento para analizar la evolución socioeconómica, habiendo dejado de ser motivo de estudio solo por la biomedicina para serlo también por los economistas y sociólogos. Es lo que han hecho Martínez Carrión y cols., con el trabajo que aparece en este número de Nutrición Hospitalaria.

Genome-wide association studies (GWAS) have found few common variants that influence fasting measures of insulin sensitivity. We hypothesized that a GWAS of an integrated assessment of fasting and dynamic measures of insulin sensitivity would detect novel common variants. We performed a GWAS of the modified Stumvoll Insulin Sensitivity Index (ISI) within the Meta-Analyses of Glucose and Insulin-Related Traits Consortium. Discovery for genetic association was performed in 16,753 individuals, and replication was attempted for the 23 most significant novel loci in 13,354 independent individuals. Association with ISI was tested in models adjusted for age, sex, and BMI and in a model analyzing the combined influence of the genotype effect adjusted for BMI and the interaction effect between the genotype and BMI on ISI (model 3). In model 3, three variants reached genome-wide significance: rs13422522 (NYAP2; P = 8.87 × 10(-11)), rs12454712 (BCL2; P = 2.7 × 10(-8)), and rs10506418 (FAM19A2; P = 1.9 × 10(-8)). The association at NYAP2 was eliminated by conditioning on the known IRS1 insulin sensitivity locus; the BCL2 and FAM19A2 associations were independent of known cardiometabolic loci. In conclusion, we identified two novel loci and replicated known variants associated with insulin sensitivity. Further studies are needed to clarify the causal variant and function at the BCL2 and FAM19A2 loci., (© 2016 by the American Diabetes Association.)

Low physical activity (PA), or sedentary lifestyle, is associated with the development of several chronic diseases. We aimed to investigate current prevalence of sedentariness and its association with diabetes and other cardiovascular risk factors. PA was evaluated in a population-based, cross-sectional, randomly sampled study conducted in 2009-2010 in Spain. International Physical Activity Questionnaire (SF-IPAQ) was used to assess PA. 4991 individuals (median age 50 years, 57% women) were studied. Prevalence of sedentariness was 32.3% for men and 39% for women (p < 0.0001). Sex differences were particularly notable (age*sex interaction, p = 0.0024) at early and older ages. Sedentary individuals had higher BMI (28 vs. 27 kg/m2) and obesity prevalence (37 vs. 26%). Low PA was present in 44, 43, and 38% of individuals with known diabetes (KDM), prediabetes/unknown-diabetes (PREDM/UKDM), and normal glucose regulation (p = 0.0014), respectively. No difference between KDM and PREDM/UKDM (p = 0.72) was found. Variables independently associated (p < 0.05) with sedentariness were age, sex, BMI, central obesity, Mediterranean diet adherence, smoking habit, HDL-cholesterol, triglycerides and dyslipidemia. Low PA is on the rise in Spain, especially among women. Sedentariness is associated with several cardiovascular risk factors and may be responsible for the increasing prevalence of obesity and diabetes in this country.

Introduction and Objectives: Di@bet.es is a national study designed to estimate the prevalence of diabetes mellitus and other cardiovascular risk factors in the Spanish adult population. The prevalence of hypertension and the degree to which it is recognized, treated, and controlled are described., Methods: The study included a sample of the Spanish population with 5048 adults aged ≥ 18 years. Patients were questioned and examined, with 3 blood pressure readings while seated and at rest to calculate the mean of the 3 readings. Hypertension was defined as systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg and/or prescription for antihypertensive drug therapy., Results: Hypertension was found in 42.6% of the Spanish adult population aged ≥ 18 years and was more common among men (49.9%) than women (37.1%). The prevalence was higher among prediabetics (67.9%) and diabetics (79.4%). Undiagnosed hypertension was identified in 37.4% of patients and was more common in men (43.3%) than in women (31.5%). Among patients with known hypertension, 88.3% were receiving drug therapy. Well-controlled blood pressure was found in only 30% and was more common among women (24.9%) than men (16%)., Conclusions: The prevalence of hypertension in Spain is high, and a considerable percentage of hypertensive patients have still not been diagnosed. Hypertension is associated with diabetes and prediabetes, and although drug therapy is increasingly common, the degree of control has not improved and remains low. Population campaigns should be developed and promoted for hypertension prevention, detection, and treatment., (Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Background and Objective: Advantages of continuous subcutaneous insulin infusion (CSII) over multiple daily injections with glargine (MDI/G) are still uncertain. We compared CSII vs. MDI/G therapy in unselected patients with type 1 diabetes using continuous glucose monitoring (CGSM). The primary end-points were glycaemic control and quality of life (QOL)., Methods: A total of 45 patients with long-term diabetes and mean HbA1c values of 8.6±1.8% (70.5±15.4mmol/mol), previously treated with MDI/NPH, were switched to MDI/G for 6 months and then, unfulfilling therapy CSII indication, were randomly assigned to CSII or MDI/G for another six months. We evaluated QOL (EsDqol) and glycaemic control by measuring HbA1c levels, rate of hypoglycaemia, ketoacidosis and CGSM data., Results: After the first phase (MDI/NPH to MDI/G) there was a significant improvement in total EsDQOL (99.72±18.38 vs. 92.07±17.65; p<0.028), a 0.5% decrease in HbA1c values (8.4±1.2 vs. 7.9±0.7% [68±9.7 vs. 63±5.5mmol/mol]; p<0.032), an improvement in glycaemic variability (standard deviation 66.9±14 vs. 59.4±16mg/dl; p<0.05), a decrease in insulin requirements (0.87±0.29 vs. 0.80±0.25U/kg; p<0.049), a decrease in number of severe hypoglycaemia episodes (0.44±0.9 vs. 0.05±0.2; p<0.014), and an increase in periods of normoglycaemia measured with CGSM (15.8±10.9% vs. 23±18.4%; p<0.003). Six months after randomization, significant improvements were seen in the HbA1c (7.9±0.7 vs. 7±0.6% [63±5.5 vs. 53±4.5mmol/mol]; p<0.001) and EsQOL (91.66±22 vs. 84.53±1.63; p<0.045) only in the CSII group. The HbA1c value was significantly lower when compared with the MDI/G group (CSII 7±0.6% [53±4.5mmol/mol] vs. MDI/G 7.6±0.9% [59.6±7.7mmol/mol]; p<0.03)., Conclusions: Intensive insulin therapy with CSII vs. MDI/G was associated with better levels of HbA1c in patients with long-term type 1 diabetes., (Copyright © 2015 Elsevier España, S.L.U. All rights reserved.)

The dyslipidemia associated with type 2 diabetes mellitus (T2DM) is an important risk factor for atherosclerotic cardiovascular disease. However, until now little attention has been paid to the role that the intestine might have. The aim of this research was to determine the relation between insulin resistance and intestinal de novo lipogenesis/lipoprotein synthesis in morbidly obese subjects and to study the effect of insulin on these processes. Jejunal mRNA expression of the different genes involved in the intestinal de novo lipogenesis/lipoprotein synthesis was analyzed in three groups of morbidly obese subjects: Group 1 with low insulin resistance (MO-low-IR), group 2 with high insulin resistance (MO-high-IR), and group 3 with T2DM and treatment with metformin (MO-metf-T2DM). In addition, intestinal epithelial cells (IECs) from MO-low-IR were incubated with different doses of insulin/glucose. In Group 2 (MO-high-IR), the jejunal mRNA expression levels of apo A-IV, ATP-citrate lyase (ACLY), pyruvate dehydrogenase (lipoamide) beta (PDHB), and sterol regulatory element-binding protein-1c (SREBP-1c) were significantly higher and acetyl-CoA carboxylase alpha (ACC1) and fatty-acid synthase lower than in Group 1 (MO-low-IR). In Group 3 (MO-metf-T2DM), only the ACLY and PDHB mRNA expressions were significantly higher than in Group 1 (MO-low-IR). The mRNA expression of most of the genes studied was significantly linked to insulin and glucose levels. The incubation of IEC with different doses of insulin and glucose produced a higher expression of diacylglycerol acyltransferase 2, microsomal triglyceride transfer protein, apo A-IV, SREBP-1c, and ACC1 when both, glucose and insulin, were at a high concentration. However, with only high insulin levels, there were higher apo A-IV, PDHB and SREBP-1c expressions, and a lower ACLY expression. In conclusion, the jejunum of MO-high-IR has a decreased mRNA expression of genes involved in de novo fatty-acid synthesis and an increase of genes involved in acetyl-CoA and lipoprotein synthesis. This effect is attenuated by metformin. In addition, the expression of most of the genes studied was found to be regulated by insulin.

Introduction: the evaluation of hospital menus should be performed periodically to suit the needs of patients. Goat cheese may have nutritional benefits, compared to cow cheese., Objectives: to evaluate patient satisfaction with the hospital menu and with the inclusion of goat cheese, given like dessert in hospital vs menu with cow cheese., Methods: a survey of hospital menu satisfaction and dessert (goat cheese (GC) vs cow cheese (CC)) in patients with basal diets was conducted., Results: 334 surveys were analyzed. 46.7% were women. The average age was 58.16 ± 15.15 years and the average stay of 11.21 ± 11.53. Acceptance of the hospital menu was rated as "good" in a high percentage of respondents (91% Temperature, presentation 94%, humidity 75% and 84% schedule). Overall satisfaction lunch (1 to 10) was 7.31 ± 2.10 en CC vs 7.39 ± 1.75 GC (ns) and dessert satisfaction was 6.93 ± 2.89 vs 6.88 ± 3.52 (ns) (respectively)., Conclusions: the overall satisfaction with the hospital menu is high and the acceptance of new dessert (QC) is equivalent to acceptance obtained with cow cheese, which could be included in the code of diets., (Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.)

Background: Abdominal obesity (AO) is a common modifiable risk factor for certain non-communicable diseases associated with enhanced oxidative stress (OS). The objective of this work was to investigate whether the interaction between antioxidant vitamin intake and OS-related polymorphisms modulates gene-associated anthropometry in a Spanish population., Methods: A total of 246 subjects with AO, and 492 age and gender matched non-AO subjects were included in the study. Anthropometric, biochemical, and OS parameters, and antioxidant dietary intake data were assessed using validated procedures. DNA from white blood cells was isolated and the genotype of seven polymorphisms from genes involved in OS (pro-oxidant and antioxidant) were analyzed using the SNPlex system. The effects of the c.-793T > C polymorphism on promoter activity and thus thioredoxin (TXN) activity were examined using reporter assays., Results: The AO group had higher 8-Oxo-2'-deoxyguanosine levels and took in less vitamin A and vitamin E compared to the non-AO group. Logistic regression analysis revealed that the rs2301241 polymorphism in TXN and rs740603 in catechol-O-methyltransferase (COMT) were associated with waist circumference (WC) and AO. Moreover, these polymorphisms were more strongly associated with variations in WC in subjects with low vitamin E intakes. A promoter assay revealed that the T to C conversion at c.-793 (rs2301241) induced a more than two fold increase in reporter gene expression., Conclusions: WC is associated both with dietary vitamin E intake and genetic variants of TXN and COMT suggesting that existence of a complex nutrigenetic pathway that involves regulation of AO.

Objective: The effects of C-peptide on adipose tissue, an organ involved in the development of obesity and insulin resistance, are not yet well known. The aim of this study was to determine whether C-peptide could be involved in the regulation of the adipocytokine synthesis in human visceral adipose tissue., Methods: The association between C-peptide and different serum adipocytokines, with an intravenous glucose tolerance test (IVGTT), and in an in vitro study in subjects without obesity and in subjects with morbid obesity were analyzed., Results: In different multiple regression analysis models, C-peptide and C-peptide increase above basal levels during total IVGTT and between 0 and 10 min were associated positively with leptin and negatively with visfatin. Rhodamine-labeled C-peptide binds to human adipocytes, and this binding was blocked with excess of unlabeled C-peptide. Exposure of human visceral explants and adipocytes from subjects with morbid obesity to C-peptide at 1 and 10 nM induced a significant increase in leptin and a decrease in visfatin secretion. In subjects without obesity, these C-peptide effects were found mainly at 10 nM. These effects can be inhibited by phosphatidylinositol 3-kinase (PI3K) or protein kinase B (PKB) inhibitors., Conclusions: C-peptide may be involved in the regulation of leptin and visfatin secretion, molecules intimately involved in energy homeostasis processes, through PI3K or PKB pathways., (© 2015 The Obesity Society.)

Background & Aims: Few prospective cohort studies have evaluated dietary iodine intake and urinary iodine concentrations in the general adult population. We assess the evolution of urinary iodine excretion and factors that may influence it in an adult population followed for 11 years., Methods: A population-based cohort study was undertaken in Pizarra (Spain). In the three study phases (baseline (n = 886), and 6 (n = 788) and 11 years later (n = 501)), participants underwent an interview and a standardized clinical examination that included a food questionnaire, and thyroid hormone and urinary iodine determinations. Subjects with thyroid dysfunction, palpable goiter or urinary iodine excretion >400 μg/L were excluded., Results: Urinary iodine increased over the years (100.6 ± 70.0 μg/L at baseline vs. 125.4 ± 95.2 μg/L at 6 years and 141.6 ± 81.4 μg/L at 11 years; p < 0.0001). Urinary iodine was significantly higher in subjects who reported iodized salt consumption and in subjects with a higher intake of dairy products (p < 0.05). Consumption of iodized salt (Risk ratio (RR) = 1.23, 95% CI [1.01-2.05]) and dairy products (RR = 2.07, 95% CI [1.01-4.23]), and a baseline urinary iodine concentration ≥100 μg/L (RR = 1.26, 95% CI [1.04-1.53]) were significantly associated with urinary iodine concentrations ≥100 μg/L at 11 years. There is no correlation between thyroid function (TSH, free triiodothyronine or free thyroxine levels) and urinary iodine concentrations in conditions of iodine sufficiency., Conclusions: The increase in urinary iodine concentrations over eleven years is associated with an increase in iodized salt intake and with the dairy products intake, and possibly with a higher iodine content of dairy products. However, individual variability in urinary iodine excretion was not fully explained by dietary iodine intake alone; previous urinary iodine concentrations were also important., (Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Results of studies examining the influence of age on thyroid function and TSH levels, in the absence of thyroid disease, remain controversial. The aim of this study was to determine the course of thyroid function over 11 years in a population with normal thyroid function., Methods: This is a population-based prospective study started in 1995-1997 (first phase), and reassessed 6 (second phase) and 11 years later (third phase)., Results: The TSH and FT4 in the third phase were significantly increased (p=0.001 and p=0.001, respectively), with the values being higher particularly from the age of 50 years. In those persons with a baseline TSH≥1.2 and <3 μIU/mL, the OR of having a TSH of 3-5 μIU/mL in the third phase was 6.10 (p=0.004). In those with a baseline TSH≥3 and ≤5 μIU/mL, the OR of having a TSH of 3-5 μIU/mL in the third phase was 20.8 (p<0.0001). Similar results were found for FT4., Conclusion: In a population free of clinical thyroid disease, TSH and FT4 values rise over the years. This increase occurs in all age groups, but depends mainly on the basal concentrations of TSH and FT4., (© 2014 John Wiley & Sons Ltd.)

Introduction and Objectives: There are no nationwide, population-based studies in Spain assessing overall cardiovascular risk. We aimed to describe cardiovascular risk and achievement of treatment goals following the 2012 European Guidelines on cardiovascular disease prevention strategy. We also investigated clinical characteristics (non-classical risk factors) associated with moderate risk., Methods: Participants (n=2310, 58% women) aged 40 to 65 years from a national population-based study (Di@bet.es Study) were identified. First, a priori high/very-high risk individuals were identified. Next, total cardiovascular risk (Systematic Coronary Risk Evaluation equation including high-density lipoprotein cholesterol) was used to assess risk of a priori non-high risk individuals. Variables independently associated with moderate versus low-risk were investigated by multiple logistic regression analysis., Results: Age-and-sex standardized (direct method) percentages of high/very-high, moderate, and low-risk were 22.8%, 43.5%, and 33.7%, respectively. Most men were at moderate (56.2%), while 55.4% of women were at low risk. Low-density lipoprotein cholesterol (< 70,<100, < 115 mg/dL) and blood pressure (<140/90 mmHg) goals for very-high, high and moderate risk were met in 15%, 26% and 46%, and 77%, 68% and 85% of the individuals, respectively. Body mass index, high triglycerides concentrations, diastolic blood pressure, and low Mediterranean diet adherence (in women) were independently associated with moderate (versus low) risk., Conclusions: Cardiovascular risk in Spain is mainly moderate in men and low in women. Achievement of treatment goals in high-risk individuals should be improved. The prevalence of non-classical cardiovascular risk factors is elevated in subjects at moderate risk, an important aspect to consider in a population-based strategy to decrease cardiovascular disease in the most prevalent group., (Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

The aim of the study was to analyze the association between aging and insulin resistance estimated by the homeostasis model assessment of insulin resistance (HOMA-IR). This work involved two studies: (1) the Di@bet.es study is a cross-sectional study including 4,948 subjects, comprising a representative sample of the adult Spanish population; (2) the Pizarra study is a population-based cohort study undertaken in Pizarra (Spain), in which 1,051 subjects were evaluated at baseline and 714 completed the 6-year follow-up study. Study variables included a clinical and demographic structured survey, a lifestyle survey, a physical examination, and an oral glucose tolerance test in subjects without diabetes. In the Di@bet.es study overall, an increase occurred in blood glucose until the age of 50, after which it remained stable (data adjusted for gender, body mass index, abnormal glucose regulation [AGR]). The HOMA-IR increased significantly with age (p = 0.01), due to a higher prevalence of obesity (p < 0.0001) and AGR (p < 0.001). In non-obese subjects without AGR, HOMA-IR values were not modified with age (p = 0.30), but they were with body mass index (p < 0.001). In the Pizarra study, the HOMA-IR was significantly lower after 6-year follow-up in the whole study population. Subjects with a HOMA-IR level higher than the 75th percentile at baseline were more likely to develop diabetes (OR 2.2, 95 % CI 1.2-3.9; p = 0.007) than subjects with a lower HOMA-IR. We concluded that age per se did not increase HOMA-IR levels, changes that might be related to higher rates of obesity and AGR in older subjects. The HOMA-IR was associated with an increased risk of developing type 2 diabetes 6 years later.

Hypoglycemia is one of the main burdens for type I Diabetes Mellitus (DM I) patients. The consequences of hypoglycemia can be quite unpleasant due to the variety of disagreeable physical and psychological symptoms it triggers. The patient's previous experience with hypoglycemia episodes will condition his psychological reaction to future episodes, promoting behavioral modifications that associate with poor glycemic control and worse prognosis, and even with developing psychological disorders, leading to fear of hypoglycemia (FH). To be able to provide tailored prevention and treatment of patients with FH it is necessary to identify the risk factors in DM I patients. We developed and validated the FH-15 scale, a novel instrument to assess FH, which showed good concurrent and predictive validity in DM I patients. In this work we aim to identify the risk factors for suffering FH by detecting DM I patients with FH using the FH-15 scale and then analyzing the association of clinical and sociodemographic variables. We found that age, needing help to resolve an episode of hypoglycemia, and a perceived lack of social support are risk factors for suffering FH., (© 2014 Scandinavian Psychological Associations and John Wiley & Sons Ltd.)

Background: Several recent studies have related short sleep duration with different health problems, though the results related with the risk of obesity and type 2 diabetes (T2D) are far from conclusive. The aim of this study was to investigate the association between night-time sleep duration and the incidence of obesity and T2D in a prospective study with a follow-up of 11 years., Material and Methods: The study comprised 1145 people evaluated in 1997-1998 and re-evaluated after 6 years and 11 years. At the three study points, subjects without known diabetes mellitus (KDM) were given an oral glucose tolerance test (OGTT). Anthropometric and biochemical variables were measured. The subjects were asked about their number of hours of night-time sleep., Results: After adjustment, the OR of becoming obese was significantly higher in subjects who slept ≤ 7 hours per night, at both the 6-year follow-up (OR = 1.99; 95% CI = 1.12-3.55) and the 11-year follow-up (OR = 2.73; 95% CI = 1.47-5.04). The incidence of T2D at the 6-year follow-up in subjects without T2D at baseline was higher in those who slept ≤ 7 hours per night (OR = 1.96; 95% CI = 1.10-3.50). However, this association was not independent of obesity, weight gain or abnormal glucose regulation at baseline. At the 11-year follow-up however there was no association between night-time sleep duration and the incidence of T2D., Conclusions: The incidence of obesity over the 11-year follow-up increased in subjects with fewer hours of night-time sleep. The incidence of T2D according to the hours of night-time sleep depended on obesity and the carbohydrate metabolism phenotype., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objective: The aim of this study was to examine possible associations between ambient temperature and obesity in the Spanish population using an ecological focus., Methods: The Di@bet.es study is a national, cross-sectional, population-based survey of cardiometabolic risk factors and their association with lifestyle., Sample: 5,061 subjects in 100 clusters., Variables: Clinical, demographic and lifestyle survey, physical examination, and blood sampling. The mean annual temperature (°C) for each study site was collected from the Spanish National Meteorology Agency (1971-2000)., Results: The prevalence rates of obesity in the different geographical areas divided according to mean annual temperature quartiles were 26.9% in quartile 1 (10.4-14.5°C), 30.5% in quartile 2 (14.5-15.5°C), 32% in quartile 3 (15.5-17.8°C), and 33.6% in quartile 4 (17.8-21.3°C) (P = 0.003). Logistic regression analyses including multiple socio-demographic (age, gender, educational level, marital status) and lifestyle (physical activity, Mediterranean diet score, smoking) variables showed that, as compared with quartile 1, the odd ratios for obesity were 1.20 (1.01-1.42), 1.35 (1.12-1.61), and 1.38 (1.14-1.67) in quartiles 2, 3, and 4, respectively (P = 0.001 for difference, P < 0.001 for trend)., Conclusions: Our study reports an association between ambient temperature and obesity in the Spanish population controlled for known confounders., (© 2014 The Obesity Society.)

Introduction: Irisin activates the thermogenic function in adipose tissues. However, little is known on the association between human irisin and different cardiometabolic risk factors. We analyse the influence of morbid obesity on irisin levels and its relation with leptin and different cardiovascular risk factors., Material and Methods: We measured the serum irisin level and the fibronectin type III domain containing 5 (FNDC5) expression in adipose tissue from 33 morbidly obese subjects and 12 nonobese subjects. We also studied the effect of leptin on FNDC5 expression., Results: Serum irisin was higher in the nonobese subjects than in morbidly obese subjects, both before (P = 0·043) and after bariatric surgery (P = 0·042). The variable that best explained the serum irisin levels in a multiple linear regression model was the waist-to-hip ratio (WHR) (R(2) = 0·201) (Beta = -0·357, P = 0·046). Those morbidly obese subjects with android-type obesity had lower serum irisin levels than those with gynecoid-type obesity, both before (P = 0·027) and after bariatric surgery (P = 0·006). Only the percentage change in WHR was associated with serum irisin levels after bariatric surgery (r = -0·529, P = 0·005). FNDC5 expression levels in subcutaneous adipose tissue (SAT) were higher in the nonobese than in the morbidly obese subjects (P = 0·042). In SAT explants from nonobese subjects, leptin (20 and 150 ng/mL) produced a decrease in FNDC5 expression (P = 0·009 and P = 0·037, respectively)., Conclusions: We showed decreased serum irisin levels in morbidly obese subjects, related mainly to WHR. FNDC5 expression could be regulated by leptin., (© 2014 Stichting European Society for Clinical Investigation Journal Foundation.)

In the last years, epigenetic processes have emerged as a promising area of complex diseases research. DNA methylation measured in Long Interspersed Nucleotide Element 1 (LINE-1) sequences has been considered a surrogate marker for global genome methylation. New findings have suggested the potential involvement of epigenetic mechanisms in Type 2 diabetes (T2DM) as a crucial interface between the effects of genetic predisposition and environmental influences. Our study evaluated whether global DNA methylation predicted increased risk from T2DM or other carbohydrate metabolism disorders in a cohort study. We used a prospective cohort intervention study and a control group. We collected phenotypic, anthropometric, biochemical, and nutritional information from all subjects. Global LINE-1 DNA methylation was quantified by pyrosequencing technology. Subjects that did not improve their carbohydrate metabolism status showed lower levels of global LINE-1 DNA methylation (63.9 ± 1.7 vs. 64.7 ± 2.4) and they practiced less intense physical activity (5.8% vs. 21.5%). Logistic regression analyses showed a significant association between LINE-1 DNA methylation and metabolic status after adjustment for sex, age, BMI, and physical activity. Our study showed that lower LINE-1 DNA methylation levels were associated with a higher risk metabolic status worsening, independent of other classic risk factors. This finding highlights the potential role for epigenetic biomarkers as predictors of T2DM risk or other related metabolic disorders.

Scope: The effects that fatty acids (FAs) exert on G protein-coupled receptor-120 (GPR120) levels, a receptor for FAs, are still unknown. We analyzed the association between GPR120 and obesity, and the FA effects on its expression., Methods and Results: GPR120 levels were analyzed in visceral adipose tissue (VAT) from nonobese and morbidly obese subject. VAT GPR120 mRNA and protein levels were lower in morbidly obese subjects (p = 0.004). After, these subjects underwent a high-fat meal. GPR120 mRNA expression in peripheral blood mononuclear cells in the fasting state was lower in morbidly obese subjects (p = 0.04), with a decrease 3 h after a high-fat meal only in morbidly obese subjects (p = 0.043). Also, incubations of visceral adipocytes from these subjects were made with different FAs. In nonobese subjects, palmitic, oleic, linoleic, and docosahexaenoic acids produced an increase in GPR120 mRNA and protein levels (p < 0.05). In morbidly obese subjects, only linoleic acid produced an increase in GPR120 mRNA and protein levels (p < 0.05)., Conclusion: Morbidly obese subjects had lower GPR120 mRNA and protein levels in VAT and a lower mRNA expression after a high-fat meal in peripheral blood mononuclear cells. The FAs effect on GPR120 mRNA and protein levels in visceral adipocytes was lower in morbidly obese subjects., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: To assess glycemic variability, oxidative stress and their relationship in children and adolescents with type 1 diabetes (T1DM) attending a summer camp., Patients and Method: Cross-sectional study that included 54 children and adolescents with T1DM aged 7-16, attending a 7 day summer camp. Sociodemographic information, clinical data, and blood glucose values measured using an Accu-Chek Nano® glucose meter were recorded. Glucose variability markers (standard deviation [SD], low blood glucose index [LBGI], high blood glucose index [HBGI], mean amplitude of glycemic excursions [MAGE] and mean of daily differences [MODD]) were calculated. Oxidative stress was assessed by the measurement of 8-iso-prostaglandin F2 alpha (PGF2α) in a 24-hour urine sample collected at the end of the camp in 14 children., Results: The Median SD, MAGE and MODD indexes were in the high range (61, 131 and 58 mg/dl, respectively), LBGI in the moderate range (3.3), and HBGI in the low range (4.5). The mean HbA1c was 7.6% and the median urinary excretion rate of 8-iso-PGF2α was 864.39 pg/mg creatinine. The Spearman correlation coefficients between markers of glycemic variability (SD, HBGI, MAGE, MODD) were significant. Non-significant correlations were found between markers of glycemic variability and urinary 8-iso-PGF2α., Conclusions: High glycemic variability was observed in children and adolescents attending a summer camp. However, no correlations were found between markers of glycemic variability and oxidative stress measured by urinary 8-iso-PGF2α. Further studies are needed to address the relationship between oxidative stress and glycemic variability in children with T1DM., (Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.)

Background and Aim: Prevalence rates of "metabolically healthy obese" (MHO) subjects vary depending on the criteria used. This study examined the prevalence and characteristics of MHO subjects and metabolically abnormal normal-weight subjects and compared the findings with the NHANES 1999-2004 study. The aims of the present study were, first, to determine the prevalence rates of MHO and MNHNO subjects using the same criteria as those of the National Health and Nutrition Examination Survey (NHANES) (1999-2004) study, and second to compare the prevalence and correlates of obese subjects who are resistant to the development of adiposity-associated cardiometabolic abnormalities (CA) and normal-weight individuals who display cardiometabolic risk factor clustering between the Spanish and the US populations., Methods and Results: Di@bet.es study is a national, cross-sectional population-based survey of 5728 adults conducted in 2009-2010. Clinical, metabolic, sociodemographic, and anthropometric data and information about lifestyle habits, such as physical activity, smoking habit, alcohol intake and food consumption, were collected. Subjects were classified according to their body mass index (BMI) (normal-weight, <25 kg/m(2); overweight, 25-29.9 kg/m(2); and obese, >30 kg/m(2)). CA included elevated blood pressure; elevated levels of triglycerides, fasting glucose, and high-sensitivity C-reactive protein (hs-CRP); and elevated homeostasis model assessment of insulin resistance (HOMA-IR) value and low high-density lipoprotein cholesterol (HDL-c) level. Two phenotypes were defined: metabolically healthy phenotype (0-1 CA) and metabolically abnormal phenotype (≥2 CA). The prevalence of metabolically abnormal normal-weight phenotype was slightly lower in the Spanish population (6.5% vs. 8.1%). The prevalence of metabolically healthy overweight and MHO subjects was 20.9% and 7.0%, respectively, while in NHANES study it was 17.9% and 9.7%, respectively. Cigarette smoking was associated with CA in each phenotype, while moderate physical activity and moderate alcohol intake were associated with being metabolically healthy. Olive oil intake was negatively associated with the prevalence of CA., Conclusions: Smoking, physical activity level, and alcohol intake contribute to the explanation of the prevalence of CA in the Spanish population, as in the US population. However in Spain, olive oil intake contributes significantly to the explanation of the variance in the prevalence of CA., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Scope: Epigenetic processes may be affected by environmental factors. DNA methylation measured in LINE-1 elements (LINE-1, long interspersed nucleotide element-1) correlates with LINE-1 DNA methylation. Variations in stearoyl CoA desaturase (SCD) activity (a key enzyme in the fatty acid metabolism) may be involved in various processes that can lead to diseases such as obesity. We evaluated whether changes in diet after a nutritional intervention would be associated with changes in LINE-1 DNA methylation and/or specific methylation of SCD1 gene promoter., Design: Prospective cohort intervention study with a control group. We recorded phenotypic, anthropometric, biochemical, and nutritional information at baseline and 1 year later. DNA methylation was quantified by pyrosequencing. LINE-1 DNA methylation and SCD1 gene promoter methylation levels were similar at the beginning of the study in both populations, whereas after a year these levels were higher in the control group (p < 0.001). In the intervention group, those subjects who lost weight showed higher levels of SCD1 gene promoter methylation after the intervention. Subjects with lower adherence to a Mediterranean diet experienced larger changes in LINE-1 methylation., Conclusion: DNA methylation levels were associated with weight change and with adherence to a Mediterranean diet., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Aims: Retinal vein occlusion (RVO) is the most frequent retinal vascular disease after diabetic retinopathy in which arterial risk factors are much more relevant than venous factors. The objective was to evaluate the role of risk factors in the development of the first episode of RVO., Subjects and Methods: One hundred patients with RVO [mean age 56 years, 42% females and mean body mass index (BMI) 27.5 kg/m(2)] were recruited consecutively from the outpatient clinic of a tertiary hospital in Valencia (Spain). All subjects underwent clinical assessment including anthropometric and blood pressure measurements and laboratory test including homocysteine, antiphospholipid antibodies (aPLAs) and thrombophilia studies. In half of the subjects, a carotid ultrasonography was performed. Three control populations matched by age, sex and BMI from different population-based studies were used to compare the levels and prevalence of arterial risk factors. One cohort of young patients with venous thromboembolic disease was used to compare the venous risk factors., Results: Blood pressure levels and the prevalence of hypertension were significantly higher in the RVO population when compared with those for the general populations. There was also a large proportion of undiagnosed hypertension within the RVO group. Moreover, carotid evaluation revealed that a large proportion of patients with RVO had evidence of subclinical organ damage. In addition, homocysteine levels and prevalence of aPLAs were similar to the results obtained in our cohort of venous thromboembolic disease., Conclusions: The results indicate that hypertension is the key factor in the development of RVO, and that RVO can be the first manifestation of an undiagnosed hypertension. Furthermore, the majority of these patients had evidence of atherosclerotic disease. Among the venous factors, a thrombophilia study does not seem to be useful and only the prevalence of hyperhomocysteinaemia and aPLAs is higher than in the general population., (© 2014 John Wiley & Sons Ltd.)

Objective: Serum levels of soluble TNF-like weak inducer of apoptosis (sTWEAK) and its scavenger receptor CD163 (sCD163) have been linked to insulin resistance. We analysed the usefulness of these cytokines as biomarkers of type 2 diabetes in a Spanish cohort, together with their relationship to food consumption in the setting of the Di@bet.es study., Research Design and Methods: This is a cross-sectional, matched case-control study of 514 type 2 diabetes subjects and 517 controls with a Normal Oral Glucose Tolerance Test (NOGTT), using data from the Di@bet.es study. Study variables included clinical and demographic structured survey, food frequency questionnaire and physical examination. Serum concentrations of sTWEAK and sCD163 were measured by ELISA. Linear regression analysis determined which variables were related to sTWEAK and sCD163 levels. Logistic regression analysis was used to estimate odd ratios of presenting type 2 diabetes., Results: sCD163 concentrations and sCD163/sTWEAK ratio were 11.0% and 15.0% higher, respectively, (P<0.001) in type 2 diabetes than in controls. Following adjustment for various confounders, the OR for presenting type 2 diabetes in subjects in the highest vs the lowest tertile of sCD163 was [(OR), 2,01 (95%CI, 1,46-2,97); P for trend <0.001]. Coffee and red wine consumption was negatively associated with serum levels of sCD163 (P = 0.0001 and; P = 0.002 for coffee and red wine intake, respectively)., Conclusions: High circulating levels of sCD163 are associated with type 2 diabetes in the Spanish population. The association between coffee and red wine intake and these biomarkers deserves further study to confirm its potential role in type 2 diabetes.

Background and Objective: Vitamin D deficiency and metabolic syndrome are 2 very common health problems in the Spanish population. It has been suggested that patients with metabolic syndrome may be vitamin D deficient more often than subjects without it and that low vitamin D levels may predispose to metabolic syndrome development. However, the results of prospective and intervention studies have been different and such relationship remains unclear. We assessed the relationship between 25-hydroxyvitamin D levels and the prevalence and incidence of metabolic syndrome., Patients and Methods: We undertook a population-based cohort study in Spain. At baseline (1996-1998), 1,226 subjects were evaluated. Follow-up visits were performed in 2002-2004 and 2005-2007.At baseline and follow-up, participants underwent an interview and a standardized clinical examination with an oral glucose tolerance test in those subjects without known diabetes. At the second visit, 25-hydroxyvitamin D levels and intact parathyroid hormone levels were measured., Results: The prevalence of metabolic syndrome at the second and third visit was 29.4 and 42.5%, respectively. Mean levels of 25-hydroxyvitamin D were lower in subjects with metabolic syndrome: 21.7 (6.21) vs 23.35 (6.29) ng/ml, P<.001.The prevalence of vitamin D deficiency (25-hydroxyvitamin D<20 ng/ml) at the second evaluation was 34.7%, with significant differences between subjects with and without metabolic syndrome(34.6 vs 26.5%, P<.01). Men with vitamin D deficiency had more frequently hypertension and metabolic syndrome than men with normal levels. Women with vitamin D deficiency had more frequently hyperglycemia, hypertension, increased waist circumference and hypertriglyceridemia. In a prospective study, 25-hydroxyvitamin D values<20 ng/ml were not significantly associated with an increased risk of developing metabolic syndrome in the next 5 years (odds ratio 0,99, 95% confidence interval 0.57-1.7, P=.97) after adjusting by sex and age., Conclusions: Vitamin D deficiency is associated with an increased prevalence but not with an increased incidence of metabolic syndrome., (Copyright © 2013 Elsevier España, S.L. All rights reserved.)

Introduction and Objectives: The aim of this study was to compare the prevalences of obesity, diabetes and other cardiovascular risk factors in the region of Andalusia with those in the rest of Spain., Methods: The Di@bet.es study is a national, cross-sectional, population-based survey of cardiometabolic risk factors and their association with lifestyle. The sample consisted of 5103 participants ≥ 18 years. The variables analyzed were clinical, demographic and lifestyle survey, physical examination, and oral glucose tolerance test. The prevalence of cardiovascular risk factors in Andalusia (n=1517) was compared with that for the rest of Spain (n=3586)., Results: In data adjusted to the Spanish population, the prevalence of diabetes (World Health Organization, 1999), hypertension (blood pressure ≥ 140/90 mmHg), high-sensitivity CRP levels (≥ 3 mg/L) and obesity (body mass index ≥ 30 kg/m(2)) were 16.3%, 43.9%, 32.0%, and 37.0% in Andalusia compared with 12.5%, 39.9%, 28.3%, and 26.6% in the rest of Spain (P<.001 for differences except P=.01 for the difference in high-sensitivity CRP levels). The corresponding figures for the Andalusia data adjusted to the Andalusian population were 15.3%, 42.3%, 31.4%, and 34.0%, respectively. Differences in diabetes, hypertension and high-sensitivity CRP were not significant in models adjusted for age, sex, and adiposity measurements. Differences in obesity were not significant in models adjusted for age, sex, educational level, marital status, work status, and physical activity (P=.086) CONCLUSIONS: This study contributes information from a national study perspective and shows a higher prevalence of cardiovascular risk factors in southern Spain, in close relation to obesity, a sedentary lifestyle, and markers of socioeconomic disadvantage., (Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.)

Introduction: Dyslipidemia is a significant contributor to the elevated CVD risk observed in type 2 diabetes mellitus. We assessed the prevalence of dyslipidemia and its association with glucose metabolism status in a representative sample of the adult population in Spain and the percentage of subjects at guideline-recommended LDL-C goals., Material and Methods: The di@bet.es study is a national, cross-sectional population-based survey of 5728 adults., Results: A total of 4776 subjects were studied. Dyslipidemia was diagnosed in 56.8% of subjects; only 13.2% of subjects were treated with lipid lowering drugs. Lipid abnormalities were found in 56.8% of Spanish adults: 23.3% with high LDL-C, 21.5% high TG, 35.8% high non-HDL-C, and 17.2% low HDL-C. Most normal subjects showed an LDL-C ≤ 3.36 mmol/l. Pre-diabetics presented similar proportion when considering a goal of 3.36 mmol/l, but only 35% of them reached an LDL-C goal ≤ 2.6 mmol/l. Finally, 45.3% of diabetics had an LDL-C ≤ 2.6 mmol/l, and only 11.3% achieved an LDL-C ≤ 1.8 mmol/l., Conclusions: Our study demonstrates a high prevalence of dyslipidemia in the adult Spanish population, and a low use of lipid-lowering drugs. Moreover, the number of subjects achieving their corresponding LDL-C goal is small, particularly in subjects at high cardiovascular risk, such as diabetics., (Copyright © 2013 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.)

Scope: Low circulating sex hormone-binding globulin (SHBG) is an independent risk factor for cardiovascular disease. Mediterranean diet has been associated with a decreased risk of cardiovascular disease. We aimed to test the hypothesis that the increase of circulating MUFA associated with olive oil consumption (primary fat source in Mediterranean diet) increases SHBG serum levels., Methods and Results: A total of 315 men were included. In these patients, nutrition data and plasma samples for SHBG assessment were obtained. In vitro studies to examine the effects of oleic and linoleic acid on SHBG production using HepG2 cells were performed. We provided evidence that SHBG serum levels were significantly higher in subjects using olive oil for cooking in comparison with subjects using sunflower oil. The SHBG levels correlated positively with MUFA (p < 0.001) and negatively with saturated fatty acids (p = 0.003). In the multiple regression analysis, MUFA were independently associated with SHBG levels and accounted for the 20.4% of SHBG variance. In vitro studies revealed that oleoyl-CoA increases SHBG production by downregulating PPAR-γ levels in HepG2 cells., Conclusion: Olive oil consumption is associated with elevated SHBG serum levels. PPAR-γ downregulation induced by oleoyl-CoA is an important underlying mechanism of such regulation., (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Little is known about the association between iodine and human milk composition. In this study, we investigated the association between iodine and different markers of oxidative stress and obesity-related hormones in human breast milk. This work is composed of two cross-sectional studies (in lactating women and in the general population), one prospective and one in vitro. In the cross-sectional study in lactating women, the breast milk iodine correlated negatively with superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-Px) activities, and with adiponectin levels. An in vitro culture of human adipocytes with 1 μM potassium iodide (KI, dose similar to the human breast milk iodine concentration) produced a significant decrease in adiponectin, GSH-Px, SOD1, and SOD2 mRNA expression. However, after 2 months of treatment with KI in the prospective study, a positive correlation was found between 24-h urinary iodine and serum adiponectin. Our observations lead to the hypothesis that iodine may be a factor directly involved in the regulation of oxidative stress and adiponectin levels in human breast milk.