Oxidative and inflammatory effects of pulmonary rehabilitation in patients with bronchiectasis. A prospective, randomized study / Efectos oxidativos e inflamatorios de la rehabilitación pulmonar en pacientes con bronquiectasia. Estudio prospectivo aleatorizado

Background: systemic inflammation and oxidative stress are important factors in the pathogenesis of bronchiectasis. Pulmonary rehabilitation (PR) is recommended for bronchiectasis, but there is no data about its effect on the inflammatory and REDOX status of these patients. Aims: to investigate the effect of PR in non-cystic-fibrosis bronchiectasis (NCFB) patients, and to compare it with the effect of PR plus a hyperproteic oral nutritional supplement (PRS) enriched with beta-hydroxy-beta-methylbutyrate (HMB) on serum inflammatory and oxidative biomarkers. Materials and methods: this was an open randomized, controlled trial. Thirty individuals (65 years old or younger with a body mass index over 18.5, older than 65 years with a body mass index over 20) were recruited from September 2013 to September 2014, and randomly assigned to receive PR or PRS. Total neutrophils, and inflammatory and oxidative biomarker levels were measured at baseline, and then at 3 and 6 months. Results: in the PRS group neutrophil levels were decreased from baseline at 6 months. A significantly different fold change was found between the PR and PRS groups. In the PR group, IL-6 and adiponectin were increased by the end of the study while TNFa levels were decreased from baseline at 6 months. REDOX biomarkers remained stable throughout the study except for 8-isoprostane levels, which were increased from baseline at 6 months in both groups of patients. Conclusion: a PR program induced a pro-oxidative effect accompanied by changes in circulating inflammatory cytokine levels in NCFB patients. Our results would also suggest a possible beneficial effect of the HMB enriched supplement on neutrophil level regulation in these patients. The information provided in this study could be useful for choosing the right therapeutic approach in the management of bronchiectasis

Introducción: la inflamación sistémica y el estrés oxidativo son factores importantes en la patogénesis de la bronquiectasia. La rehabilitación pulmonar (PR) está recomendada en los sujetos con bronquiectasias, pero no hay datos sobre sus posibles efectos sobre el estado inflamatorio y REDOX de estos pacientes. Objetivos: investigar el efecto de la PR en pacientes con bronquiectasias no asociadas a fibrosis quística (NCFB) sobre los biomarcadores oxidativos e inflamatorios, y compararlo con los efectos de la PR junto con la suplementación oral de un suplemento hiperproteico (PRS) enriquecido con beta-hidroxi-beta-metilbutirato (HMB). Material y métodos: ensayo clínico abierto, aleatorizado y controlado. Treinta pacientes (de 65 años o menos con un índice de masa corporal por encima de 18,5, y mayores de 65 años con un índice de masa corporal de más de 20) se aleatorizaron para recibir PR o PRS. Los niveles circulantes de neutrófilos totales y los de biomarcadores de estado inflamatorio y oxidativo se determinaron al inicio del estudio y a los 3 y 6 meses. Resultados: los niveles de neutrófilos en el grupo de PRS se redujeron desde el inicio a los 6 meses, presentando una tasa de cambio significativamente diferente según el tratamiento. En el grupo de PR, la IL-6 y la adiponectina aumentaron al final del estudio, mientras que los niveles de TNFa disminuyeron desde el inicio a los 6 meses. Los biomarcadores de estrés oxidativo se mantuvieron estables durante todo el estudio excepto por los niveles de 8-isoprostano, que aumentaron desde el inicio a los 6 meses en ambos grupos de pacientes. Conclusión: el programa de PR indujo un efecto pro-oxidativo acompañado de cambios en los niveles de citoquinas inflamatorias circulantes en pacientes con NCFB. Nuestros resultados también sugieren un posible efecto beneficioso del suplemento nutricional sobre la regulación de los niveles de neutrófilos de estos pacientes

Relationship between glucose control, glycemic variability, and oxidative stress in children with type 1 diabetes / Relación entre control metabólico, variabilidad glucémica y estrés oxidativo en niños con diabetes tipo 1

Introduction: Few studies assessing the relationship between oxidative stress and glycemic variability in children with type 1 diabetes mellitus (T1DM) are available, and most of them reported no significant results. Objective: To assess the relationship between glucose control, glycemic variability, and oxidative stress as measured by urinary excretion of 8-iso-prostanglandin F2-alpha (8-iso-PGF2alfa) in children with T1DM. Materials and methods: A cross-sectional study including 25 children with T1DM. Participants were evaluated during five days in two different situations: 1st phase during a summer camp, and 2nd phase in their everyday life at home. The following data were collected in each study phase:. Six capillary blood glucose measurements per day. Mean blood glucose (MBG) levels and glucose variability parameters, including standard deviation, coefficient of variation, and mean amplitude of glycemic excursions (MAGE), were calculated. - Capillary HbA1c level. - 24-h urine sample to measure 8-iso-PGF2alfa. Results: There were no statistically significant differences in urinary 8-iso-PGF2alfa levels (142 ± 37 vs. 172 ± 61 pg/mg creatinine) and glucose control and glycemic variability parameters between both phases. In the 2nd phase, statistically significant correlations were found between urinary 8-iso-PGF2alfa and HbA1c levels (r = 0.53), MBG (r = 0.72), standard deviation (r = 0.49), and MAGE (r = 0.42). No significant correlations between glucose control, glycemic variability and urinary 8-iso-PGF2alfa excretion were found in the 1st phase. Conclusions: A significant correlation was found between glycemic variability and HbA1c level and urinary 8-iso-PGF2α excretion in a group of children with T1DM during their daily lives. Additional studies are needed to confirm this finding and to explore its long-term impact on health

Introducción: En niños con diabetes tipo 1 (DM1) hay pocos estudios que evalúen la relación entre estrés oxidativo y variabilidad glucémica, y la mayoría de ellos no encuentran resultados significativos. Objetivo: Evaluar la relación entre control metabólico, variabilidad glucémica y estrés oxidativo medido por la excreción urinaria de 8-iso-prostaglandina F2 alfa (8-iso-PGF2alfa) en niños con DM1. Material y método: Estudio transversal que incluyó 25 niños con DM1. Los participantes fueron evaluados durante 5 días en 2 situaciones diferentes: 1.a fase durante un campamento de verano y 2.a fase durante su actividad habitual en domicilio. En cada fase se recogieron:- Seis determinaciones de glucemia capilar diarias. Se calcularon glucemia media y parámetros de variabilidad glucémica: desviación estándar, coeficiente de variación y «mean amplitude of glycemic excursions» (MAGE). - HbA1c capilar. - Muestra de orina de 24h para la determinación de 8-iso-PGF2alfa. Resultados: No se encontraron diferencias estadísticamente significativas en excreción urinaria de 8-iso-PGF2alfa (142 ± 37 vs. 172 ± 61 pg/mg creatinina) y parámetros de control y variabilidad glucémicos entre las fases. En la 2.a fase se observaron correlaciones estadísticamente significativas entre 8-iso-PGF2alfa urinario con HbA1c (r = 0,53), glucemia media (r = 0,72), desviación estándar (r = 0,49) y MAGE (r = 0,42). En la 1.a fase del estudio no se han detectado correlaciones significativas. Conclusiones: Se ha encontrado una correlación significativa entre parámetros de variabilidad glucémica y HbA1c con la excreción urinaria de 8-iso-PGF2alfa en un grupo de niños con DM1 evaluados durante su vida diaria. Son necesarios más estudios para confirmar estos resultados y evaluar el impacto a largo plazo sobre la salud

Relationship between glucose control, glycemic variability, and oxidative stress in children with type 1 diabetes.

INTRODUCTION: Few studies assessing the relationship between oxidative stress and glycemic variability in children with type 1 diabetes mellitus (T1DM) are available, and most of them reported no significant results. OBJECTIVE: To assess the relationship between glucose control, glycemic variability, and oxidative stress as measured by urinary excretion of 8-iso-prostanglandin F2-alpha (8-iso-PGF2α) in children with T1DM. MATERIALS AND METHODS: A cross-sectional study including 25 children with T1DM. Participants were evaluated during five days in two different situations: 1st phase during a summer camp, and 2nd phase in their everyday life at home. The following data were collected in each study phase:. - Six capillary blood glucose measurements per day. Mean blood glucose (MBG) levels and glucose variability parameters, including standard deviation, coefficient of variation, and mean amplitude of glycemic excursions (MAGE), were calculated. - Capillary HbA1c level. - 24-h urine sample to measure 8-iso-PGF2α. RESULTS: There were no statistically significant differences in urinary 8-iso-PGF2α levels (142±37 vs. 172±61pg/mg creatinine) and glucose control and glycemic variability parameters between both phases. In the 2nd phase, statistically significant correlations were found between urinary 8-iso-PGF2α and HbA1c levels (r=0.53), MBG (r=0.72), standard deviation (r=0.49), and MAGE (r=0.42). No significant correlations between glucose control, glycemic variability and urinary 8-iso-PGF2α excretion were found in the 1st phase. CONCLUSIONS: A significant correlation was found between glycemic variability and HbA1c level and urinary 8-iso-PGF2α excretion in a group of children with T1DM during their daily lives. Additional studies are needed to confirm this finding and to explore its long-term impact on health.

Dairy Product Consumption and Metabolic Diseases in the Di@bet.es Study.

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.

Comparison of the Effects of Goat Dairy and Cow Dairy Based Breakfasts on Satiety, Appetite Hormones, and Metabolic Profile.

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, AUCGLP-1 was inversely associated with the AUChunger and AUCdesire-to-eat after the G-Breakfast, whereas triglyceride levels were directly associated with AUCCSI 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.

Inflammation and Oxidation Biomarkers in Patients with Cystic Fibrosis: The Influence of Azithromycin.

OBJECTIVE: In addition to their antibiotic effect, macrolides appear to modulate the inflammatory response in cystic fibrosis (CF) and could influence oxidative stress. The objective of this study was to assess oxidation biomarkers and levels of inflammation and to determine whether there is an association between these parameters and the intake of macrolides. MATERIALS AND METHODS: The subjects included in this cross-sectional study were, on the one hand, clinically stable patients with CF and, on the other, healthy controls. The following serum and plasma inflammatory and oxidative stress biomarkers were measured: interleukin-6 (IL-6), reactive C protein (RCP), tumor necrosis alpha (TNF-α), glutathione peroxidase (GPx), total antioxidant capacity (TAC), catalase (CAT), and superoxide dismutase (SOD), together with markers of lipid peroxidation (8-isoprostanes and thiobarbituric acid reactive substances [TBARS]). Clinical, anthropometric, lung function, radiological, and analytical variables (albumin, prealbumin, vitamins, and zinc) were also recorded. RESULTS: We studied 36 adults with CF and 41 controls. No differences were observed in age, gender, or anthropometric variables. The patients had significantly higher levels of IL-6, TNF-α, RCP, TBARS, and isoprostanes, and lower levels of SOD than the controls. Twenty-three of the patients were treated with azithromycin, and they had more severe clinical and radiological parameters than those who were not but nevertheless presented significantly lower levels of TNF-α. No differences were observed in the markers of oxidation. CONCLUSION: Inflammation and oxidation biomarkers were increased in patients with CF compared with controls. The use of azithromycin was associated with reduced TNF-α levels and did not influence oxidation parameters.

Dietary fatty acids modulate adipocyte TNFa production via regulation of its DNA promoter methylation levels.

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.

[SATISFACTION WITH HOSPITAL MENU AND INCLUSION OF GOAT CHEESE AS DESSERT COMPARED WITH COW CHEESE]. / SATISFACCIÓN CON EL MENÚ HOSPITALARIO E INCORPORACIÓN DEL QUESO DE CABRA COMO POSTRE EN COMPARACIÓN CON EL QUESO DE VACA.

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.

Introducción: la valoración de los menús hospitalarios debe realizarse periódicamente para adecuarlos a las necesidades de los pacientes. El queso de cabra podría tener ventajas nutricionales, en comparación con el de vaca. Objetivos: evaluar la satisfacción de los pacientes con el menú hospitalario y con la incorporación del queso de cabra, dado como postre en el menú hospitalario vs queso de vaca. Material y métodos: se realizó una encuesta de satisfacción del menú hospitalario y del postre (queso de cabra (QC) vs queso de vaca (QV)) en pacientes con dietas basales. Resultados: se analizaron 334 encuestas. El 46,7% fueron mujeres. La edad media fue de 58,16 ± 15,15 años y la estancia media de 11,21 ± 11,53. La aceptación del menú hospitalario fue valorado como buena en un alto porcentaje de los encuestados (temperatura 91%, presentación 94%, humedad 75% y horario 84%). La satisfacción global del almuerzo (1 al 10) fue 7,31 ± 2,10 en QV vs 7,39 ± 1,75 QC (ns) y del postre 6,93 ± 2,89 vs 6,88 ± 3,52 (ns) respectivamente. Los pacientes que habitualmente no toman queso de cabra (57%) tampoco tomaron postre en el 50% de los casos, frente a los que sí toman en su domicilio (42,98%), que no ingirieron nada del postre solo en el 8% (p < 0.01) Conclusiones: la satisfacción global con el menú hospitalario es alta y la aceptación del nuevo postre (QC) es equivalente a la obtenida con el queso de vaca, por lo que podría incluirse en el código de dietas.

Satisfacción con el menú hospitalario e incorporación del queso de cabra como postre en comparación con el queso de vaca / Satisfaction with hospital menu and inclusion of goat cheese as dessert compared with cow cheese

Introducción: la valoración de los menús hospitalarios debe realizarse periódicamente para adecuarlos a las necesidades de los pacientes. El queso de cabra podría tener ventajas nutricionales, en comparación con el de vaca. Objetivos: evaluar la satisfacción de los pacientes con el menú hospitalario y con la incorporación del queso de cabra, dado como postre en el menú hospitalario vs queso de vaca. Material y métodos: se realizó una encuesta de satisfacción del menú hospitalario y del postre (queso de cabra (QC) vs queso de vaca (QV)) en pacientes con dietas basales. Resultados: se analizaron 334 encuestas. El 46,7% fueron mujeres. La edad media fue de 58,16 ± 15,15 años y la estancia media de 11,21 ± 11,53. La aceptación del menú hospitalario fue valorado como buena en un alto porcentaje de los encuestados (temperatura 91%, presentación 94%, humedad 75% y horario 84%). La satisfacción global del almuerzo (1 al 10) fue 7,31 ± 2,10 en QV vs 7,39 ± 1,75 QC (ns) y del postre 6,93 ± 2,89 vs 6,88 ± 3,52 (ns) respectivamente. Los pacientes que habitualmente no toman queso de cabra (57%) tampoco tomaron postre en el 50% de los casos, frente a los que sí toman en su domicilio (42,98%), que no ingirieron nada del postre solo en el 8% (p < 0.01). Conclusiones: la satisfacción global con el menú hospitalario es alta y la aceptación del nuevo postre (QC) es equivalente a la obtenida con el queso de vaca, por lo que podría incluirse en el código de dietas (AU)

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 (AU)

Evolution of urinary iodine excretion over eleven years in an adult population.

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.

Type 2 diabetes mellitus in relation to global LINE-1 DNA methylation in peripheral blood: a cohort study.

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.

Night-time sleep duration and the incidence of obesity and type 2 diabetes. Findings from the prospective Pizarra study.

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.

Methylation levels of the SCD1 gene promoter and LINE-1 repeat region are associated with weight change: an intervention study.

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.

Modifications of the homeostasis model assessment of insulin resistance index with age.

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.

Does dietary iodine regulate oxidative stress and adiponectin levels in human breast milk?

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.

Oleic acid increases hepatic sex hormone binding globulin production in men.

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.

Stress hyperglycaemia in hospitalized patients with coronary artery disease and type 2 diabetes risk.

AIMS: (i) To evaluate glucometabolic status of patients without known diabetes hospitalized due to coronary artery disease (CAD), (ii) to assess markers of systemic inflammation determined during admission and to evaluate their relationship with glucometabolic status and (iii) to analyse usefulness of HbA1c determined during admission in patients with CAD to detect abnormal glucose regulation (AGR). MATERIALS & METHODS: We studied 440 patients with CAD admitted to the cardiology ward. Patients were grouped in four groups during admission according to clinical data, fasting plasma glucose and HbA1c: diabetes, HbA1c > 5·9%, stress hyperglycaemia (SH) and normal. In 199 subjects without known diabetes, an oral glucose tolerance test (OGTT) was performed 3 months after discharge, and they were reclassified according to WHO 1998 criteria. Biochemical and inflammatory markers were measured. RESULTS: The OGTT showed that 27·4% of subjects without known diabetes at admission had diabetes, 11·2% had impaired fasting glucose + impaired glucose tolerance, 33·5% impaired glucose tolerance, 3·6% impaired fasting glucose, and 24·4% normal glucose metabolism. Odds ratio for having diabetes 3 months after discharge in HbA1c > 5·9% group was 5·91 (P < 0·0001) and in SH group was 1·82 (P = 0·38). The best HbA1c cut-off point to predict AGR was 5·85%. HbA1c levels during admission were highly predictive of having AGR (AUC ROC 0·76 [95% CI 0·67-0·84]). CONCLUSION: We reported a high prevalence of AGR in subjects with CAD. Stress hyperglycaemia in patients with CAD was not associated with an increased risk of diabetes 3 months later. HbA1c in patients hospitalized with CAD was a useful tool to detect AGR.

Metabolically healthy but obese, a matter of time? Findings from the prospective Pizarra study.

BACKGROUND: Prospective longitudinal studies evaluating the relevance of "Metabolically Healthy but Obese" (MHO) phenotype at risk for type 2 diabetes mellitus (T2D) and cardiovascular diseases are few and results are contradictory. METHODS: As a representative of the general population, 1051 individuals were evaluated in 1997-1998 and re-evaluated after 6 years and 11 years. Subjects without known T2D were given an oral glucose tolerance test. Anthropometric and biochemical variables were measured. Four sets of criteria were considered to define MHO subjects besides body mass index ≥30 kg/m(2): A: Homeostatic Model of Assessment-Insulin Resistance Index (HOMA-IR) <90th percentile; B: HOMA-IR <90th percentile, high-density lipoprotein cholesterol >40 mg/dL in men and high-density lipoprotein cholesterol >50 mg/dL in women, triglycerides <150 mg/dL, fasting glucose <110 mg/dL, and blood pressure ≤140/90 mm Hg; C: HOMA-IR <90th percentile, triglycerides <150 mg/dL, fasting glucose <110 mg/dL, and blood pressure ≤140/90 mm Hg; D: HOMA-IR <90th percentile, triglycerides <150 mg/dL, and fasting glucose <110 mg/dL. Subjects with T2D at baseline were excluded from the calculations of incidence of T2D. RESULTS: The baseline prevalence of MHO phenotype varied between 3.0% and 16.9%, depending on the set of criteria chosen. Metabolically nonhealthy obese subjects were at highest risk for becoming diabetic after 11 years of follow-up (odds ratio = 8.20; 95% confidence interval = 2.72-24.72; P < .0001). In MHO subjects the risk for becoming diabetic was lower than in metabolically nonhealthy obese subjects, but this risk remained significant (odds ratio = 3.13; 95% confidence interval = 1.07-9.17; P = .02). In subjects who lost weight during the study, the association between MHO phenotype and T2D incidence disappeared, even after adjusting for HOMA-IR. CONCLUSIONS: The results suggest that MHO is a dynamic concept that should be taken into account over time. As a clinical entity, it may be questionable.

C-reactive protein and incidence of type 2 diabetes in the Pizarra study.

AIM: To determine the association between serum levels of high-sensitivity C-reactive protein (hs-CRP) and the incidence of type 2 diabetes in a prospective cohort from southern Spain (Pizarra study). MATERIALS AND METHODS: The study formed part of the Pizarra cohort study, a prospective study started in 1995 with a follow-up of 11 years. Anthropometric and metabolic variables were measured at baseline and at 6 years and 11 years of follow-up. All subjects underwent an oral glucose tolerance test. Serum levels of TNFα and its receptors, hs-CRP, IL-6, leptin, adiponectin and FABP4 were measured at 6 years of follow-up. RESULTS: After adjusting for age, sex and obesity, subjects with levels of hs-CRP> 2.9 mg/L in the second study (2003-4) had a higher risk of developing type 2 diabetes by the third study (2008-9) (OR = 7.97; 95% CI = 1.72-36.89; P = 0.008), and subjects with adiponectin levels > 13.2 mg/L had a lower risk of developing type 2 diabetes (OR = 0.23, P = 0.02). High values of hs-CRP and high values of adiponectin were associated positively (OR = 8.26; 95% CI = 1.84-37.19; P = 0.006) and negatively (OR = 0.17; 95% CI = 0.04-0.69; P = 0.01), respectively, with the risk of having HbA1c ≥ 6.5% at 11 years of follow-up. CONCLUSIONS: Subjects with high serum hs-CRP levels and low serum adiponectin levels have a higher risk of developing type 2 diabetes within five years.

Prevención de la diabetes mellitus tipo 2 / Prevention of diabetes mellitus type 2

La diabetes mellitus tipo 2 (DM2) es uno de los más importantes factores de riesgo de enfermedadcardiovascular. El incremento de la prevalencia en todo el mundo está generando una gran preocupación clínica y sociosanitaria. Los estudios de intervención clínica, como el UKPDS, han demostrado queaunque se puede mejorar el control metabólico de la DM2 con programas de intervención intensiva,estos son muy costosos y no consiguen un óptimo control metabólico. Es por esto que en este momentouno de los grandes objetivos ante la DM2 es el de la prevención. La historia natural de la DM2 essuficientemente conocida y sabemos que cuando se diagnostica hay un período previo en el que haexistido un «estado prediabético» que se comporta como factor de riesgo vascular. En los últimos años numerosos estudios han demostrado que la prevención de la DM2 es posible. En esta revisión se hace unaaproximación crítica de la situación actual (AU)

Diabetes mellitus type 2 (DM2) is one of the most important risk factors for cardiovascular disease. Theincreasing prevalence worldwide is generating a great health and social concern. Clinical interventionstudies such as the UKPDS have shown that although the metabolic control of DM2 may improve withintensive intervention programs, these are highly expensive and do not lead to an optimal metaboliccontrol. For this reason, one of the main challenges in DM2 at present is its prevention. The naturalhistory of DM2 is sufficiently well known and we know that before it is diagnosed, there is a former, oftenlasting years, ‘‘pre-diabetic state’’ that behaves as a vascular risk factor. In recent years numerous studieshave shown that prevention of DM2 is possible. We critically review here the current situation of thedisease (AU)