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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.

This investigation has been supported by CIBERDEM (Ministerio de Economía, Industria y Competitividad-ISCIII), Ministerio de Sanidad, Servicios Sociales e Igualdad-ISCIII, Instituto de Salud Carlos III (research Grants PI18/01165, PI17/02136, PI14/00710, PI14/01104, PI14/00970, PI14/00874, PIE14/00031) and cofunding by the European Regional Development Fund (ERDF) “A way to build Europe”. LifeScan España (Madrid, Spain) kindly donated the glucometers and test strips for capillary glucose measurements. Cristina Maldonado-Araque is a researcher in the ‘Rio Hortega’ program (CM19/00186) financed by the Instituto de Salud Carlos III. Gemma Rojo-Martinez belongs to the Nicolás Monardes research program of the Consejería de Salud (C-0060-2012; Junta de Andalucía, Spain)., García-Escobar E., Valdés S., Soriguer F., Vendrell J., Urrutia-Etxebarria I.M., Maldonado-Araque C., Ortega E., Ocón P., Montanya E., Menéndez E., Lago-Sampedro A., González-Frutos T., Gomis R., Goday A., García-Serrano S., Galán-García J.L., Castell C., Bordiú E., Badía R., Aguilera-Venegas G., Girbés J., Gaztambide S., Delgado E., Chaves F.J., Castaño L., Calle-Pascual A., Rojo-Martínez G., Franch-Nadal J.

Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (Ministerio de Economía, Industria y Competitividad-Instituto de Salud Carlos III), Instituto de Salud Carlos III (PI11-02755), (PI17-02136), Consejería de Salud y familias (PI-0144-2018), European Regional Development Fund ‘‘A way to build Europe.’’, Maldonado-Araque, C., Valdés, S., Badiá-Guillén, R., Lago-Sampedro, A., Colomo, N., Garcia-Fuentes, E., Gutierrez-Repiso, C., Goday, A., Calle-Pascual, A., Castaño, L., Castell, C., Delgado, E., Menendez, E., Franch-Nadal, J., Gaztambide, S., Girbés, J., Chaves, F.J., Soriguer, F., Rojo-Martínez, G.

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

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.

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 mu g/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 mu g/g, there was a positive correlation between UI and thyrotropin levels (beta = 0.152, p < 0.001) and a negative correlation between UI and free triiodothyronine levels (beta=-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.

Resumen Introduccion y objetivos El Di@bet.es es un estudio nacional disenado con el objetivo de estimar la prevalencia de diabetes mellitus y otros factores de riesgo cardiovascular en la poblacion adulta espanola. Se presenta la prevalencia de hipertension arterial y en que grado se reconoce, se trata y se controla. Metodos Se incluye una muestra de la poblacion espanola con 5.048 adultos de edad ≥ 18 anos. Se realizo un interrogatorio clinico y una exploracion que incluyo 3 lecturas de presion arterial en reposo y sedestacion para calcular la media de las 3 lecturas. Se definio hipertension como presion arterial sistolica ≥ 140 mmHg y/o presion arterial diastolica ≥ 90 mmHg y/o en tratamiento farmacologico antihipertensivo. Resultados El 42,6% de la poblacion adulta espanola de edad ≥ 18 anos es hipertensa, mas los varones (49,9%) que las mujeres (37,1%). La prevalencia fue superior entre los prediabeticos (67,9%) y diabeticos (79,4%). El 37,4% de los hipertensos estan sin diagnosticar, mas los varones (43,3%) que las mujeres (31,5%). Toman tratamiento farmacologico el 88,3% de los hipertensos conocidos y solo el 30% tiene la presion arterial controlada, mas las mujeres (24,9%) que los varones (16%). Conclusiones La prevalencia de hipertension en Espana es alta y un importante porcentaje de pacientes hipertensos aun estan sin diagnosticar. La hipertension se asocio con diabetes y prediabetes, y aunque el tratamiento farmacologico es cada vez mas frecuente, no logra mejorar el grado de control, que continua siendo bajo. Es importante desarrollar y promocionar campanas poblacionales de prevencion, deteccion y tratamiento de la hipertension arterial.

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).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.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; p0.028), a 0.5% decrease in HbA1c values (8.4±1.2 vs. 7.9±0.7% [68±9.7 vs. 63±5.5mmol/mol]; p0.032), an improvement in glycaemic variability (standard deviation 66.9±14 vs. 59.4±16mg/dl; p0.05), a decrease in insulin requirements (0.87±0.29 vs. 0.80±0.25U/kg; p0.049), a decrease in number of severe hypoglycaemia episodes (0.44±0.9 vs. 0.05±0.2; p0.014), and an increase in periods of normoglycaemia measured with CGSM (15.8±10.9% vs. 23±18.4%; p0.003). 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]; p0.001) and EsQOL (91.66±22 vs. 84.53±1.63; p0.045) 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]; p0.03).Intensive insulin therapy with CSII vs. MDI/G was associated with better levels of HbA1c in patients with long-term type 1 diabetes.

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 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.

We have investigated the epigenetic regulation by dietary fatty acids of Vegfb levels in rats’ white adipose tissue and 3T3-L1 cells. 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. 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. 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.

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.

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.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 excretion400 μg/L were excluded.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; p0.0001). Urinary iodine was significantly higher in subjects who reported iodized salt consumption and in subjects with a higher intake of dairy products (p0.05). 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.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.

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.

A B S T R A C T 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 (

Resumen Introduccion y objetivos En Espana no se dispone de estudios poblacionales de ambito nacional en los que se haya evaluado el riesgo cardiovascular total. El objetivo del estudio es describir el riesgo cardiovascular y la consecucion de los objetivos terapeuticos segun lo establecido en la guia europea de 2012 para la estrategia de prevencion de la enfermedad cardiovascular. Se investigaron tambien las caracteristicas clinicas (factores de riesgo no clasicos) asociadas a un riesgo moderado. Metodos Se selecciono a los participantes (n = 2.310; el 58% mujeres), de entre 40 y 65 anos de edad, de un estudio de base poblacional de ambito nacional (estudio Di@bet.es). En primer lugar, se identifico a los sujetos con un riesgo a priori alto o muy alto. A continuacion, se utilizo el riesgo cardiovascular total (ecuacion Systematic Coronary Risk Evaluation con inclusion del colesterol unido a lipoproteinas de alta densidad) para evaluar el riesgo de los individuos con un riesgo a priori no alto. Se investigaron las variables con asociacion independiente con el riesgo moderado frente al riesgo bajo, utilizando para ello un analisis de regresion logistica multiple. Resultados Los porcentajes estandarizados respecto a edad y sexo (metodo directo) de los participantes con riesgo alto/muy alto, moderado y bajo fueron del 22,8, el 43,5 y el 33,7% respectivamente. La mayoria de los varones tenian un riesgo moderado (56,2%), mientras que el 55,4% de las mujeres tenian riesgo bajo. Alcanzaron los objetivos de colesterol unido a lipoproteinas de baja densidad ( Conclusiones El riesgo cardiovascular en Espana es principalmente moderado en los varones y bajo en las mujeres. Debe mejorarse la consecucion de los objetivos terapeuticos por los individuos de alto riesgo. La prevalencia de factores de riesgo cardiovascular no clasicos esta aumentada en los individuos de riesgo moderado, lo cual es un aspecto importante que tener en cuenta en una estrategia de base poblacional para reducir las enfermedades cardiovasculares en el grupo de mayor prevalencia.

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.

Objective: To assess glycaemic variability, oxidative stress and their relationship in children and adolescents with type 1 diabetes (T1DM) attending a summer camp. Patients and methods: 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 metre were recorded. Glucose variability markers (standard deviation [SD], low blood glucose index [LBGI], high blood glucose index [HBGI], mean amplitude of glyacemic 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-h 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 glycaemic variability (SD, HBGI, MAGE, MODD) were significant. Non-significant correlations were found between markers of glycaemic variability and urinary 8-iso-PGF2α. Conclusions: High glycaemic variability was observed in children and adolescents attending a summer camp. However, no correlations were found between markers of glycaemic variability and oxidative stress measured by urinary 8-iso-PGF2α. Further studies are needed to address the relationship between oxidative stress and glycaemic variability in children with T1DM. Resumen: Objetivos: Analizar variabilidad glucémica, el estrés oxidativo y la relación entre ambos en un grupo de en niños y adolescentes con diabetes tipo 1 (DM1) que asistieron a un campamento. Pacientes y método: Estudio transversal que incluyó a 54 niños con DM1 entre 7 y 16 años de edad que asistieron a un campamento de verano de 7 días. Se recogieron datos sociodemográficos, clínicos y valores de glucemia capilar medidos con un glucómetro Accu-Chek Nano®. Se calcularon los marcadores de variabilidad glucémica: desviación estándar (DE), índice de glucemia baja (LBGI), índice de glucemia elevada (HBGI), amplitud media de las excursiones glucémicas (MAGE) y media de las diferencias diarias (MOOD). El estrés oxidativo fue evaluado mediante la medición de 8-iso-prostaglandina F2 alfa (PGF2α) en una muestra de orina de 24 h recogida en 14 niños al final del campamento. Resultados: La mediana de DE, MAGE y MOOD se encontraron en un rango elevado (61, 131 y 59 mg/dl, respectivamente), LBGI en la categoría de riesgo moderado (3,3) y HBGI en la categoría de riesgo bajo (4,5). La media de HbA1c fue del 7,6%. La media de la tasa de excreción urinaria de 8-iso-PGF2α fue 864,39 pg/mg creatinina. No se encontraron correlaciones estadísticamente significativas entre marcadores de variabilidad glucémica y 8-iso PGF2α urinario. Conclusiones: Se ha objetivado una alta variabilidad glucémica en niños y adolescentes con DM1 asistentes a un campamento de verano. Sin embargo, no se han encontrado correlaciones entre marcadores de variabilidad glucémica y de estrés oxidativo medido por 8-iso-PGF2α urinario.

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

cope 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.

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.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).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.

Resumen Introduccion y objetivos El objetivo de este estudio fue comparar la prevalencia de obesidad, diabetes mellitus y otros factores de riesgo cardiovascular en la region de Andalucia con las prevalencias en el resto de Espana. Metodos El estudio Di@bet.es es un estudio poblacional transversal de ambito nacional sobre prevalencia de factores de riesgo cardiometabolicos y su asociacion con el estilo de vida. Formaron la muestra 5.103 participantes de edad ≥ 18 anos. Se realizo una encuesta clinica, demografica y de estilo de vida, una exploracion fisica y una prueba de sobrecarga oral de glucosa. La prevalencia de factores de riesgo cardiovascular en Andalucia (n = 1.517) se comparo con la del resto de Espana (n = 3.586). Resultados Segun los datos ajustados para la poblacion espanola, las prevalencias de diabetes mellitus (Organizacion Mundial de la Salud, 1999), hipertension (presion arterial ≥ 140/90 mmHg), titulos elevados de PCR ultrasensible (≥ 3 mg/l) y obesidad (indice de masa corporal ≥ 30) fueron del 16,3, el 43,9, el 32,0 y el 37,0% en Andalucia, en comparacion con el 12,5, el 39,9, el 28,3 y el 26,6% en el resto de Espana (p Conclusiones Este estudio aporta informacion desde una perspectiva nacional y muestra una prevalencia de factores de riesgo cardiovascular superior en el sur de Espana, con estrecha correlacion con la obesidad, el estilo de vida sedentario e indicadores de una situacion socioeconomica desfavorecida.

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. Methods and results 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.

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.

Summary 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/m2] 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.

Introduction and objectives To assess the patterns of use of 8 therapeutic drug groups for the treatment of diabetes mellitus and other cardiovascular risk factors, and to identify sociodemographic and health determinants of their use in the overall Spanish population. Methods A representative sample of the Spanish population within the Di@bet.es study, a cross-sectional population-based survey, was included. Study variables: sociodemographic, clinical, and lifestyle data; physical examination, and an oral glucose tolerance test in patients without known diabetes mellitus. Furthermore, patients were systematically queried about current medication use, and 8 pharmacotherapeutic groups were evaluated: lipid-lowering therapy, antihypertensives, oral hypoglycemic agents, insulin, thyroid hormone, uricosurics, psychoactive drugs, and nonsteroidal anti-inflammatory drugs. Results Sixty-six percent of the Spanish population was taking at least one medication. Therapeutic drug use was associated with age, independently of the higher prevalence of diabetes mellitus, hypertension, or hyperlipidemia in older patients. Sex disparities were found in the use of lipid-lowering agents, allopurinol, levothyroxine, nonsteroidal anti-inflammatory drugs, and psychoactive drugs. Use of psychoactive drugs was related to education level, work status, physical activity, smoking, and alcohol consumption. Almost 30% of patients with diabetes mellitus were taking 6 or more medications daily. Diabetes mellitus was associated with greater use of antihypertensives, lipid-lowering agents, and nonsteroidal anti-inflammatory drugs. Conclusions Age and sex are the most important factors determining therapeutic drug use. Lifestyle patterns and sociocultural factors have an impact only on psychoactive drug use. Diabetes mellitus is associated with greater use of antihypertensives, lipid-lowering agents, and nonsteroidal anti-inflammatory drugs.

Resumen Introduccion y objetivos Evaluar el patron de consumo de ocho grupos de farmacos para el tratamiento de la diabetes mellitus y otros factores de riesgo cardiovascular; identificar en la poblacion espanola los determinantes sociodemograficos y de salud asociados al consumo de aquellos. Metodos El estudio Di@bet.es es una encuesta poblacional transversal que comprende una muestra significativa de la poblacion adulta espanola. Variables de estudio: datos sociodemograficos, clinicos y de estilo de vida; exploracion fisica, y sobrecarga oral de glucosa. Ademas, se pregunto sistematicamente la medicacion consumida y se analizaron ocho grupos de farmacos: hipolipemiantes, antihipertensivos, antidiabeticos orales, insulina, hormona tiroidea, uricosuricos, psicofarmacos y antiinflamatorios no esteroideos. Resultados El 66% de la poblacion toma alguno de los farmacos estudiados. El consumo de dichos medicamentos se asocia con la edad, independientemente de la prevalencia de diabetes mellitus, hipertension o dislipemia. Se han encontrado diferencias significativas entre sexos en el consumo de hipolipemiantes, hormona tiroidea, uricosuricos, antiinflamatorios no esteroideos y psicofarmacos. El consumo de psicofarmacos se asocio significativamente con nivel educativo, situacion laboral, actividad fisica y consumo de tabaco y alcohol. El 30% de los sujetos con diabetes mellitus tomo mas de seis farmacos diarios. La diabetes mellitus se asocio significativamente con un mayor consumo de antihipertensivos, hipolipemiantes y antiinflamatorios no esteroideos. Conclusiones La edad y el sexo son los factores mas importantes que determinan el consumo de farmacos. El estilo de vida y el nivel sociocultural afectan solo al uso de psicofarmacos. La diabetes mellitus se asocia a un mayor consumo de antihipertensivos, hipolipemiantes y antiinflamatorios no esteroideos.

cope 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.

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.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-IR90th percentile, high-density lipoprotein cholesterol40 mg/dL in men and high-density lipoprotein cholesterol50 mg/dL in women, triglycerides150 mg/dL, fasting glucose110 mg/dL, and blood pressure ≤140/90 mm Hg; C: HOMA-IR90th percentile, triglycerides150 mg/dL, fasting glucose110 mg/dL, and blood pressure ≤140/90 mm Hg; D: HOMA-IR90th percentile, triglycerides150 mg/dL, and fasting glucose110 mg/dL. Subjects with T2D at baseline were excluded from the calculations of incidence of T2D.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.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.

SummaryObjective Modifications in lifestyle, diet and certain clinical events are major contributors for the high prevalence of obesity. The aim of this study was to assess factors associated with weight gain in a population of Spanish adults. Design The study was undertaken in two population-based cohorts from the north and the south of Spain (baseline and after 6 years). The Asturias Study, in the north, included 1034 persons aged 30–75 years, of whom 701 were reassessed. The Pizarra Study, in the south, included 1226 persons aged 18–65 years, of whom 783 were re-evaluated. Both studies involved a nutritional questionnaire, a physical examination and an oral glucose tolerance test (OGTT). Results During the follow-up, 32·3% of the participants lost weight, 34·5% gained fewer than 4 kg and 33·2% gained more than 4 kg. Weight gain was greater in persons younger than 50 years and in those with an initial body mass index below 30. Weight gain was associated with a greater incidence of type 2 diabetes mellitus (T2DM) and abnormal glucose tolerance, whereas weight loss in persons with these disorders was associated with a normal OGTT 6 years later. Persons who took less exercise and those who reported a higher daily calorie intake experienced greater weight gain. Conclusion The longitudinal changes in weight affect the development of T2DM and abnormal glucose tolerance. The weight is a dynamic phenomenon affected by several social customs.

Summary Background & aims Oxidative stress is believed to play an important role in the pathophysiology of bronchiectasis. The aims of this study were to evaluate the oxidative stress status in bronchiectasis patients. Methods This cross-sectional study included 90 clinically stable adults with bronchiectasis of any aetiology (36 with cystic fibrosis [CF] and 54 without CF) plus 50 healthy controls. Plasma and serum oxidative stress biomarkers were measured using commercial kits. Cellular oxidative stress biomarkers in white blood cells (mitochondrial membrane potential, intracellular glutathione, superoxide anion and hydrogen peroxide) were analyzed by flow cytometry. Results Compared with the control group, the catalase activity and lipid peroxidation (TBARs and 8-isoprostanes) were significantly increased in the patient group and the total antioxidant capacity and the activity of superoxide dismutase were decreased. Intracellular superoxide anion and hydrogen peroxide were significantly elevated in the patients versus the controls in total leukocytes, lymphocytes, monocytes and neutrophils. Compared to the controls, the mitochondrial membrane potential was significantly lower in neutrophils and intracellular glutathione in monocytes. No significant differences were observed between CF and non-CF bronchiectasis patients in the oxidative stress biomarkers studied. Conclusions Biomarkers of oxidative stress, both in plasma and intracellular were raised in patients with bronchiectasis compared with controls. No differences were seen in the CF patients compared with the others.

Background and Aims: Mediterranean diet (MedDiet) is causally related to diabetes and is a dietary pattern recommended to individuals with diabetes. We investigated MedDiet adherence in individuals with prediabetes and unknown (PREDM/UKDM) or known diabetes (KDM) compared to those with normal glucose metabolism (NORMAL). Methods: This was a national, population-based, cross-sectional, cluster-sampling study. MedDiet adherence was scored (MedScore, mean ± SD 24 ± 5) using a qualitative food frequency questionnaire. Logistic regression was used to examine the association between MedScore and PREDM/UKDM or KDM versus control subjects. Results: We evaluated 5,076 individuals. Mean age was 50 years, 57% were female, 826 (582/244) were PREDM/UKDM, 478 were KDM and 3,772 were NORMAL. Mean age increased across MedScore tertiles (46, 51 and 56 years, p < 0.0001). Higher age-adjusted adherence to MedDiet (5-unit increment in the MedScore) was associated with lower and nondifferent odds (OR, 95% CI) of prevalent PREDM/UKDM (0.88, 0.81-0.96, p = 0.001) and KDM (0.97, 0.87-1.07, p = 0.279), respectively, compared to individuals in the NORMAL group. Conclusions: In a representative sample of the whole Spanish population, MedDiet adherence is independently associated with PREDM/UKDM. Therapeutic intervention may be, in part, responsible for the lack of differences in adherence observed between the KDM and NORMAL groups. However, reverse causation bias cannot be ruled out in cross-sectional studies.

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.

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.

Fat-free mass depletion has been related to increased inflammatory activity and to increased morbidity and mortality in chronic respiratory diseases. The aims of our study were to determine the nutritional status and serum levels of adipocytokines and inflammatory cytokines in patients with bronchiectasis of any etiology and their relation with respiratory parameters. A cross-sectional study was designed that included patients aged >14 years with diagnostic criteria for bronchiectasis. Anthropometric parameters; a diet questionnaire; hand grip dynamometry; levels of leptin, adiponectin, interleukin-6 (IL-6), tumor necrosis factor-α, and ultrasensitive C-reactive protein; as well as respiratory parameters (ie, clinical, radiologic, and spirometric values) were assessed. Ninety-three clinically stable patients were recruited, 43 with cystic fibrosis, 31 with noncystic fibrosis bronchiectasis, and 19 with cystic fibrosis transmembrane conductance regulator-related bronchiectasis. Fat-free mass depletion was present in 31% of patients, with no differences according to the etiology of the bronchiectasis. Correlations were found between inflammatory cytokines (ie, IL-6) and exacerbations, bronchorrea, forced expiratory volume in 1 second, and Bhalla score. Patients with worse respiratory disease severity, malnutrition, and diabetes had significantly higher levels of IL-6. Adiponectin correlated significantly and positively with fat mass and fat mass index and negatively with fat-free mass, fat-free mass index, and hand dynamometry. Leptin correlated positively with body mass index, fat mass and fat mass index, and negatively with fat-free mass, fat-free mass index, and dynamometry. Patients with bronchiectasis present a high percentage of fat-free mass depletion, independent of the etiology of the disease. The levels of inflammatory cytokines (especially IL-6) may be useful markers of disease severity. Adiponectin levels were higher in patients with fat-free mass depletion.

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

Eur J Clin Invest 2012 Abstract Background Although high-sensitivity C-reactive protein (hs-CRP) is currently used as a risk marker of cardiovascular disease, it has been suggested that genetic, clinical, biochemical or environmental factors could modify hs-CRP levels. The aim of this study was to investigate sources of interindividual hs-CRP variability in the Spanish population. Materials and methods A representative sample of the Spanish population within the di@bet.es study was used. Study variables included a clinical and demographic structured survey, a lifestyle survey, a physical examination, plasmatic hs-CRP and other biochemical parameters. Results Median and interquartile range of plasma hs-CRP values were 1·73 ± 2·75 mg/dL. Thirty per cent of the study population had hs-CRP levels above 3 mg/dL and 38% from 1 to 3 mg/dL. Body mass index was the strongest factor associated with moderate and high hs-CRP levels. Age, sex, waist-to-hip ratio, weight increase, plasma lipid levels, glucose metabolism (HOMA-IR and abnormal glucose regulation categories), pharmacological treatment (lipid-lowering agents, psychotropic drugs and levothyroxine), smoking, physical activity, different dietary patterns, quality of life and educational level were all significantly associated with hs-CRP levels. Interactions were observed between variables. These interactions modulated the effect of previously described factors on hs-CRP. Conclusions Thirty per cent of the Spanish population have hs-CRP levels considered to represent a cardiovascular risk. Different clinical, anthropometric, biochemical and environmental variables modulate hs-CRP levels. In addition, multiple interactions between variables complicate the interpretation of hs-CRP values.

The aim of this prospective, adult population-based study was to analyse the prevalence of type 2 diabetes mellitus in relation to the intake of cows' milk and the prevalence of anti-beta-lactoglobulin (anti-β-LG) antibodies. Measurements were made of weight, height, levels of anti-islet antibodies, anti-β-LG antibodies and tumour necrosis factor alpha (TNF-α) in all the participants. The likelihood of having positive anti-β-LG antibodies was higher in subjects who consumed milk more frequently. Subjects who consumed milk less than once per day were more likely to have type 2 diabetes than those who consumed milk more than once per day. The levels of TNF-α were significantly higher in individuals with positive anti-β-LG antibodies and in those who consumed milk more often. The prevalence of anti-β-LG antibodies was associated with the intake of milk and with the TNF-α levels, but not with the prevalence of type 2 diabetes. © 2012 Elsevier Ltd., This study was supported by the CIBER in Diabetes and Associated Metabolic Disorders (Instituto de Salud Carlos III); Ministerio de Ciencia e Innovación (JCI-2010-08372) and Consejería Innovación, Ciencia y Empresa (P09-CTS-5125).

We evaluated a telemedicine system in patients with type 1 diabetes who had optimized treatment with an insulin pump and a real-time continuous glucose monitoring system. We conducted a prospective, one-year study of 15 subjects. Three medical visits took place: pre-baseline, baseline and at 6 months. Each month the subjects transmitted information from the glucose meter, glucose sensor and insulin pump. We adjusted the treatment and returned the information by email. We evaluated psychological and metabolic variables, including HbA1c, hypoglycaemia, hyperglycaemia and glucose variability. At baseline the mean age of the subjects was 40 years and the mean duration of diabetes was 22 years. There was a significant reduction in HbA1c (7.50 to 6.97%) at 6 months, a significant increase in the number of self-monitoring blood glucose checks per day (5.2 to 6.2), and significant improvements in variability: MODD, mean of daily difference (67 to 53) and MAGE, mean amplitude of glycaemic excursions (136 to 102). There were significant improvements in quality of life (92 to 87), satisfaction with the treatment (34 to 32) and less fear of hypoglycaemia (36 to 32). Adult subjects with type 1 diabetes on treatment with a continuous insulin infusion system and a real time glucose sensor and who have acceptable metabolic control and optimized treatment can benefit from the addition of a telemetry system to their usual outpatient follow-up.

Background and objetive: The aim of this study was to validate the ability of the Finnish Diabetes Risk Score (FINDRISC) to predict the risk of DM2 in a population of south-eastern Spain (Pizarra Study). Subjects and methods: The Pizarra Study is a population-based prospective study developed in the town of Pizarra (Malaga). The first phase of the study was conducted in 1997-1998, including 1051 individuals aged 18-65 years randomly selected from the municipal census of the town. In 2003-2004 the subjects participating in the first study were reassessed. 824 individuals completed the second phase of the study (78.4%). All participants without known diabetes underwent an oral glucose tolerance test both at baseline and follow-up. We evaluated the ability of the FINDRISC to detect undiagnosed DM2 (first phase: cross-sectional study) and in predicting the incidence of DM2 (second phase: cohort study). Results: The test showed good results both to detect undiagnosed DM2 (ROC-AUC 0.74) and to predict incident DM2 (ROC-AUC 0.75). The best prediction of risk of incident DM2 was found in those subjects with fasting glucose > 100 mg/dl and a FINDRISC 9 (OR: 19.37; 95%IC: 8,86-42,34; P < .0001).

Aims We studied the changes in the incidence of lower limb amputation (LLA) in Andalusia from 1998 to 2006 in the population with and without diabetes. Methods We undertook a retrospective study of all LLA performed in Andalusia in people aged 30 years old, with or without diabetes, between 1 January 1998 and 31 December 2006. We obtained the crude and standardized incidence rates by year, and sex for three periods: 1998–2000, 2001–2003 and 2004–2006 and calculated the RR of requiring LLA in patients with diabetes. To test for time trend, Poisson regression models were fitted. Results A total of 16,210 LLA were carried out in Andalusia, 72.6% in patients with diabetes mellitus and 66.4% in men. In the population with diabetes the standardized incidence of all LLA was found to be 344.0 per 100,000 (95% CI, 315.4–372.4) in 2004–2006. There was an estimated incidence increase for all LLA by 14% and for minor LLA by 13.6% in 2004–2006. In people with diabetes the RR increased by 31.6% as compared to the first period. Conclusions Despite the implementation of a care plan for patients with diabetes, the incidence of LLA has not fallen in Andalusia in recent years.

ObjectiveChanges in eating habits may be influential in the ever-increasing rate of childhood obesity. Our aim was to determine whether those children who consume olive oil have a lower risk of weight gain compared with children who consume other oils.Design and methodsThe study included 18 girls and 74 boys, all aged 13–166 months. A survey was completed for each subject about eating habits and physical activity. A sample of subcutaneous adipose tissue was also obtained for cellular study. Data were recorded on the mean size of the adipocytes, the number of preadipocytes, and the concentration of particular fatty acids. The weight and height of the children were measured 13 months later.ResultsThe likelihood that after 1 year the children would have increased their body mass index (BMI)Z-score above the initial score was less in the children who consumed only olive oil (odds ratio (OR)=0.22; 95% confidence interval (CI): 0.08–0.63;P=0.005). These results remained after adjusting for age, physical activity and BMI (OR=0.19; 95% CI: 0.06–0.61;P=0.005) and after adjusting for age, physical activity and adipocyte volume (OR=0.15; 95% CI: 0.04–0.52;P=0.003).ConclusionsDiets with mono unsaturated fatty acid (MUFA)-rich olive oil could reduce the risk of obesity in childhood.

Eur J Clin Invest 2011 Abstract Background Increased accumulation of fat results from an imbalance between energy expenditure and intake, being modulated by different environmental and genetic factors. Uncoupling proteins (UCPs) are mitochondrial carrier proteins able to spend energy generating heat. Therefore, variations in these genes are good candidates as potential modulators of body fat accumulation. Our aim was to investigate the possible association of genetic variations of the gene codifying the UCP2 protein with obesity and fat distribution. Design We performed a cross-sectional study in 2367 individuals from two population-based studies from different regions of Spain. The Hortega Study included 1436 individuals (693 women) 21–85 years old, and the Pizarra Study included 931 individuals (584 women) 18–65 years old. We evaluated three polymorphisms of the UCP2 gene. Results The TT genotype of the rs660339 polymorphism and the AA genotype of the rs659366 polymorphism of the UCP2 gene were significantly associated with higher waist circumference in the Hortega Study. Furthermore, subjects carrying both genotypes (TT+AA) also showed higher central adiposity compared with other genotypes. This association was also present in the Pizarra Study. Moreover, in the pooled population, we found a stronger association with waist circumference. Even, we found association with BMI. Furthermore, rs659366 polymorphism was associated with the risk of abdominal obesity (P = 0·04: OR = 1·3; CI = 1·01–1·67). Conclusions Polymorphisms of the UCP2 gene (rs660339 and rs659366) were associated with central obesity. This study shows association between the UCP2 gene and the susceptibility to obesity and body fat distribution in a south European population.

Eur J Clin Invest 2012; 42 (1): 79–85 Abstract Aim To evaluate the association between serum levels of testosterone, sex hormone-binding globulin (SHBG) and calculated bioavailable testosterone (bioT), and the risk of type 2 diabetes mellitus (T2D) in a prospective cohort from southern Spain (Pizarra study). Research design and methods The study was performed in 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 and 11 years of follow-up. Total testosterone (TT), SHBG and calculated bioT were determined at the 6-year follow-up. Results The levels of TT and bioT in men were negatively associated with the risk of obesity, T2D and the metabolic syndrome. In women, the levels of TT and bioT were associated positively with the risk of insulin resistance. The levels of SHBG were associated negatively with the risk of T2D, obesity and insulin resistance in both men and women. For all groups, the association was higher at the 11-year follow-up. Conclusions Low levels of testosterone and SHBG increase the risk of T2D in men, and high levels of testosterone increase the risk of insulin resistance in women. The association between TT levels and the risk of T2D is not completely independent of other variables, such as exposure time, adiposity, insulin resistance or SHBG levels. This study also shows that the different responses between men and women are probably because of the protective effect of SHBG, levels of which are higher in women than in men.

Eur J Clin Invest 2011; 41 (11): 1202–1209 Abstract Background Different studies, mostly cross-sectional, have found an association between low levels of thyroid hormones, even within the normal range, and a greater body mass index. The aim of this study was to determine the association between thyroid function and the risk for obesity. Materials and methods In this population-based prospective study, measurements were made of anthropometric parameters, thyroid hormone function and urinary iodine in a cohort of the Pizarra Study (n = 937), and repeated 6 years later (n = 784). At the second point, measurements were also made of leptin and adiponectin. Results Among the persons who were not obese at the start of the study, the odds ratio (OR) of becoming obese for those in the fourth quartile (Q4) for free triiodothyronine (FT3) (versus those in Q1) was 2·94 (1·46–5·90) (P = 0·005). The OR of becoming obese in persons in Q4 of FT4 (versus those in Q1) was 3·06 (1·23–7·43) (P = 0·01). Those persons in Q4 of weight gain had a higher FT3 at the 6-year follow-up than those whose weight gain was in Q1 (P

Fundamento y objetivo Evaluar la hipotesis de que valores elevados de glucemia se asocian con menores valores sericos de acido urico, en 2 poblaciones independientes. Pacientes y metodo La primera poblacion procede del Estudio Pizarra, estudio prospectivo con 1.226 sujetos que se clasificaron segun su situacion metabolica tras una sobrecarga oral de glucosa. Se midieron variables antropometricas, valores basales de insulina, acido urico y resistencia a la insulina segun el Homeostasis Model Assessment (HOMA-IR). La segunda muestra procede de la base de datos del Hospital Universitario Carlos Haya (Malaga), que recoge 81.754 sucesivas peticiones analiticas de hemoglobina glucosilada (HbA1c) realizadas a lo largo de 30 meses. Resultados En el Estudio Pizarra los valores de glucosa se relacionaron con los valores de acido urico en ambos sexos. En la segunda muestra los valores de acido urico de mujeres siguieron una relacion en forma de campana con la HbA1c, incrementandose hasta valores de HbA1c del 7% y descendiendo a medida que la HbA1c aumentaba (p

Background Insulin has several biological functions besides glycaemic control. We investigated and compared the effects of six different commercial insulins on adipocyte cell differentiation, the lipolytic activity of differentiated cells, and the expression levels of genes involved in adipogenesis and associated with insulin activity. Materials and methods 3T3-L1 cells were induced to differentiate with six commercial insulins: glargine, lispro, aspart, detemir, NPH and regular recombinant human insulin (used as control). Cell differentiation, lipolysis and gene expression were measured at day 7 (D7) and day 10 (D10) after induction of differentiation in these cells. Results The highest values of cell differentiation and lipolysis were found at D10 for all the insulins used. Preadipocyte differentiation differed at both times depending on the insulin used, with detemir insulin being the least adipogenic. The PPARγ mRNA level varied according to the insulin and was a good genetic marker of adipogenesis at D7. Cells treated with glargine insulin showed the highest lipolysis and HSL expression on both days. Gene expression levels of InsR, SREBP-1c and SCD-1 differed depending on the insulin studied. Conclusions Detemir insulin was the least adipogenic of the insulins tested, whereas treatment with glargine insulin tended to produce the highest lipolysis levels. Under these experimental conditions, the modifications made in commercial insulins to improve glycaemic control also affect adipocyte differentiation, the lipolysis level of differentiated cells, and the expression of different genes that can modify metabolic pathways independently of glucose metabolism. © 2011 The Authors. European Journal of Clinical Investigation © 2011 Stichting European Society for Clinical Investigation Journal Foundation.

Resumen Objetivo Valorar la funcion tiroidea en los tres trimestres de gestacion en mujeres sanas suplementadas con yodo y definir los limites de referencia de la normalidad de esta poblacion. Diseno Estudio descriptivo sobre la mujer gestante para definir los limites de normalidad de hormonas tiroideas en esta poblacion. Emplazamiento Jaen y Osuna. Poblacion Gestantes sanas. Metodos Determinacion de hormonas tiroideas en los tres trimestres de gestacion en mujeres sanas suplementadas con yodo. Resultados Cuatrocientas veintinueve gestantes fueron suplementadas con yodo para mantener nivel de yoduria en los limites de normalidad. Las concentraciones de T4-l estuvieron entre 0,60 y 1,06 para el primer trimestre, entre 0,43 y 0,85 ng/dl en el segundo trimestre y entre 0,40 y 0,82 ng/dl en el tercer trimestre. Para la TSH los valores de referencia son: 0,23 y 4,18 μUI/ml en el primer trimestre, 1,78 y 3,89 μUI/ml en el segundo trimestre y 2,01 y 4,30 μUI/ml en el tercer trimestre. Para T3-l los limites en el primer trimestre es de 2,33 a 3,84 pg/ml, entre 2,04 y 3,51 pg/ml en el segundo trimestre y entre 1,99 y 3,46 pg/ml en el tercer trimestre. Conclusion Los limites de referencia para nuestra poblacion teniendo en cuenta los percentiles 3 y 97 estan muy por debajo del recomendado por nuestro laboratorio de referencia, lo que obliga a redefinir estas concentraciones para evitar diagnosticar de forma incorrecta de hipotiroxinemia a la mujer gestante sana.

Hypoglycemia is the most common adverse event associated with insulin treatment in diabetes. The consequences of hypoglycemia can be quite aversive and potentially life threatening. The physical sequelae provide ample reason for patients to fear hypoglycemia and avoid episodes. For these reasons, our purpose in this study was to develop a new measure that explores specific fear of hypoglycemia (FH) in adult patients with type 1 diabetes and to examine its psychometric properties. The instrument developed to assess FH was initially made up of 20 items, of which 18 were negative and 2 were positive, assessed on a 5-point Likert scale (1-5). This scale was completed by 229 patients with type 1 diabetes. Additionally, a structured interview and a closed question called subjective fear of hypoglycemia were included as diagnostic criteria. A factor analysis employing the principal-components method and promax rotation was carried out, resulting in a new scale composed of 15 items. Three factors (fear, avoidance, and interference) were obtained and explained 58.27% of the variance. The scale showed good internal consistency (Cronbach's α = .891) and test-retest reliability (r = .908, p < .001), as well as adequate concurrent and predictive validity. The cutoff score that provided the highest overall sensitivity and specificity was set at 28 points. The Fear of Hypoglycemia 15-item scale (FH-15) demonstrated good reliability and validity. This study suggests that the new instrument may serve as a valuable measure of specific FH for use in research and clinical practice.