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The aim of this study was to combine nuclear magnetic resonance-based metabolomics and machine learning to find a glucose-independent molecular signature associated with future type 2 diabetes mellitus development in a subgroup of individuals from the Di@bet.es study.The study group included 145 individuals developing type 2 diabetes mellitus during the 8-year follow-up, 145 individuals matched by age, sex and BMI who did not develop diabetes during the follow-up but had equal glucose concentrations to those who did and 145 controls matched by age and sex. A metabolomic analysis of serum was performed to obtain the lipoprotein and glycoprotein profiles and 15 low molecular weight metabolites. Several machine learning-based models were trained.Logistic regression performed the best classification between individuals developing type 2 diabetes during the follow-up and glucose-matched individuals. The area under the curve was 0.628, and its 95% confidence interval was 0.510-0.746. Glycoprotein-related variables, creatinine, creatine, small HDL particles and the Johnson-Neyman intervals of the interaction of Glyc A and Glyc B were statistically significant.The model highlighted a relevant contribution of inflammation (glycosylation pattern and HDL) and muscle (creatinine and creatine) in the development of type 2 diabetes as independent factors of hyperglycemia.Copyright © 2023. Published by Elsevier B.V.

BackgroundAssociations between increased dietary fat and decreased carbohydrate intake with circulating HDL and non-HDL cholesterol have not been conclusively determined.ObjectiveWe assessed these relations in 8 European observational human studies participating in the European Nutritional Phenotype Assessment and Data Sharing Initiative (ENPADASI) using harmonized data.MethodsDietary macronutrient intake was recorded using study-specific dietary assessment tools. Main outcome measures were lipoprotein cholesterol concentrations: HDL cholesterol (mg/dL) and non-HDL cholesterol (mg/dL). A cross-sectional analysis on 5919 participants (54% female) aged 13–80 y was undertaken using the statistical platform DataSHIELD that allows remote/federated nondisclosive analysis of individual-level data. Generalized linear models (GLM) were fitted to assess associations between replacing 5% of energy from carbohydrates with equivalent energy from total fats, SFAs, MUFAs, or PUFAs with circulating HDL cholesterol and non-HDL cholesterol. GLM were adjusted for study source, age, sex, smoking status, alcohol intake and BMI.ResultsThe replacement of 5% of energy from carbohydrates with total fats or MUFAs was statistically significantly associated with 0.67 mg/dL (95% CI: 0.40, 0.94) or 0.99 mg/dL (95% CI: 0.37, 1.60) higher HDL cholesterol, respectively, but not with non-HDL cholesterol concentrations. The replacement of 5% of energy from carbohydrates with SFAs or PUFAs was not associated with HDL cholesterol, but SFAs were statistically significantly associated with 1.94 mg/dL (95% CI: 0.08, 3.79) higher non-HDL cholesterol, and PUFAs with –3.91 mg/dL (95% CI: –6.98, –0.84) lower non-HDL cholesterol concentrations. A statistically significant interaction by sex for the association of replacing carbohydrates with MUFAs and non-HDL cholesterol was observed, showing a statistically significant inverse association in males and no statistically signi

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

Background: Joint data analysis from multiple nutrition studies may improve the ability to answer complex questions regarding the role of nutritional status and diet in health and disease. Objective: The objective was to identify nutritional observational studies from partners participating in the European Nutritional Phenotype Assessment and Data Sharing Initiative (ENPADASI) Consortium, as well as minimal requirements for joint data analysis. Methods: A predefined template containing information on study design, exposure measurements (dietary intake, alcohol and tobacco consumption, physical activity, sedentary behavior, anthropometric measures, and sociodemographic and health status), main health-related outcomes, and laboratory measurements (traditional and omics biomarkers) was developed and circulated to those European research groups participating in the ENPADASI under the strategic research area of 'diet-related chronic diseases.' Information about raw data disposition and metadata sharing was requested. A set of minimal requirements was abstracted from the gathered information. Results: Studies (12 cohort, 12 cross-sectional, and 2 case-control) were identified. Two studies recruited children only and the rest recruited adults. All studies included dietary intake data. Twenty studies collected blood samples. Data on traditional biomarkers were available for 20 studies, of which 17 measured lipoproteins, glucose, and insulin and 13 measured inflammatory biomarkers. Metabolomics, proteomics, and genomics or transcriptomics data were available in 5, 3, and 12 studies, respectively. Although the study authors were willing to share metadata, most refused, were hesitant, or had legal or ethical issues related to sharing raw data. Forty-one descriptors of minimal requ

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

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.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.Age-and-sex standardized (direct method) percentages of high/very-high, moderate, and low-risk were 22.8%, 43.5%, and 33.7%, respectively. Most men were at moderate (56.2%), while 55.4% of women were at low risk. Low-density lipoprotein cholesterol (< 70,<100, < 115 mg/dL) and blood pressure (<140/90 mmHg) goals for very-high, high and moderate risk were met in 15%, 26% and 46%, and 77%, 68% and 85% of the individuals, respectively. Body mass index, high triglycerides concentrations, diastolic blood pressure, and low Mediterranean diet adherence (in women) were independently associated with moderate (versus low) risk.Cardiovascular risk in Spain is mainly moderate in men and low in women. Achievement of treatment goals in high-risk individuals should be improved. The prevalence of non-classical cardiovascular risk factors is elevated in subjects at moderate risk, an important aspect to consider in a population-based

Objective: Serum levels of soluble TNF-like weak inducer of apoptosis (sTWEAK) and its scavenger receptor CD163 (sCD163) have been linked to insulin resistance. We analysed the usefulness of these cytokines as biomarkers of type 2 diabetes in a Spanish cohort, together with their relationship to food consumption in the setting of the Di@bet.es study. Research Design and Methods: This is a cross-sectional, matched case-control study of 514 type 2 diabetes subjects and 517 controls with a Normal Oral Glucose Tolerance Test (NOGTT), using data from the Di@bet.es study. Study variables included clinical and demographic structured survey, food frequency questionnaire and physical examination. Serum concentrations of sTWEAK and sCD163 were measured by ELISA. Linear regression analysis determined which variables were related to sTWEAK and sCD163 levels. Logistic regression analysis was used to estimate odd ratios of presenting type 2 diabetes. Results: sCD163 concentrations and sCD163/sTWEAK ratio were 11.0% and 15.0% higher, respectively, (P<0.001) in type 2 diabetes than in controls. Following adjustment for various confounders, the OR for presenting type 2 diabetes in subjects in the highest vs the lowest tertile of sCD163 was [(OR), 2,01 (95%CI, 1,46-2,97); P for trend <0.001]. Coffee and red wine consumption was negatively associated with serum levels of sCD163 (P = 0.0001 and; P = 0.002 for coffee and red wine intake, respectively). Conclusions: High circulating levels of sCD163 are associated with type 2 diabetes in the Spanish population. The association between coffee and red wine intake and these biomarkers deserves further study to confirm its potential role in type 2 diabetes. © 2014 Rojo-Martínez et al.

10.1371/journal.pone.0101250, Objective: Serum levels of soluble TNF-like weak inducer of apoptosis (sTWEAK) and its scavenger receptor CD163 (sCD163) have been linked to insulin resistance. We analysed the usefulness of these cytokines as biomarkers of type 2 diabetes in a Spanish cohort, together with their relationship to food consumption in the setting of the Di@bet.es study. Research Design and Methods: This is a cross-sectional, matched case-control study of 514 type 2 diabetes subjects and 517 controls with a Normal Oral Glucose Tolerance Test (NOGTT), using data from the Di@bet.es study. Study variables included clinical and demographic structured survey, food frequency questionnaire and physical examination. Serum concentrations of sTWEAK and sCD163 were measured by ELISA. Linear regression analysis determined which variables were related to sTWEAK and sCD163 levels. Logistic regression analysis was used to estimate odd ratios of presenting type 2 diabetes. Results: sCD163 concentrations and sCD163/sTWEAK ratio were 11.0% and 15.0% higher, respectively, (P,0.001) in type 2 diabetes than in controls. Following adjustment for various confounders, the OR for presenting type 2 diabetes in subjects in the highest vs the lowest tertile of sCD163 was [(OR), 2,01 (95%CI, 1,46–2,97); P for trend ,0.001]. Coffee and red wine consumption was negatively associated with serum levels of sCD163 (P = 0.0001 and; P = 0.002 for coffee and red wine intake, respectively). Conclusions: High circulating levels of sCD163 are associated with type 2 diabetes in the Spanish population. The association between coffee and red wine intake and these biomarkers deserves further study to confirm its potential role in type 2 diabetes.

Acknowledgments: Sara Borrell Postdoctoral program; BFU 2011 and CIBER Obesidad y Nutricion (Instituto de Salud Carlos Tercero (ISCIII), Ministerio de Ciencia e Innovacion). Juan de la Cierva Program (Ministerio de Educación y Ciencia)., The adipokine resistin is an insulin-antagonizing factor that also plays a regulatory role in inflammation, immunity, food intake, and gonadal function and also regulates growth hormone (GH) secretion in rat adenopituitary cells cultures with the adipokine. Although adipose tissue is the primary source of resistin, it is also expressed in other tissues, including the pituitary. The aim of this study is to investigate the possible action of resistin on the lipid metabolism in the pituitary gland in vivo (rats in two different nutritional status, fed and fast, treated with resistin on acute and a chronic way) and in vitro (adenopituitary cell cultures treated with the adipokine). Here, by a combination of in vivo and in vitro experimental models, we demonstrated that central acute and chronic administration of resistin enhance mRNA levels of the lipid metabolic enzymes which participated on lipolysis and moreover inhibiting mRNA levels of the lipid metabolic enzymes involved in lipogenesis. Taken together, our results demonstrate for the first time that resistin has a regulatory role on lipid metabolism in the pituitary gland providing a novel insight in relation to the mechanism by which this adipokine can participate in the integrated control of lipid metabolism., Depto. de Genética, Fisiología y Microbiología, Fac. de Ciencias Biológicas, TRUE, pub

The adipokine resistin is an insulin-antagonizing factor that also plays a regulatory role in inflammation, immunity, food intake, and gonadal function and also regulates growth hormone (GH) secretion in rat adenopituitary cells cultures with the adipokine. Although adipose tissue is the primary source of resistin, it is also expressed in other tissues, including the pituitary. The aim of this study is to investigate the possible action of resistin on the lipid metabolism in the pituitary gland in vivo (rats in two different nutritional status, fed and fast, treated with resistin on acute and a chronic way) and in vitro (adenopituitary cell cultures treated with the adipokine). Here, by a combination of in vivo and in vitro experimental models, we demonstrated that central acute and chronic administration of resistin enhance mRNA levels of the lipid metabolic enzymes which participated on lipolysis and moreover inhibiting mRNA levels of the lipid metabolic enzymes involved in lipogenesis. Taken together, our results demonstrate for the first time that resistin has a regulatory role on lipid metabolism in the pituitary gland providing a novel insight in relation to the mechanism by which this adipokine can participate in the integrated control of lipid metabolism.

Objective. To evaluate the association between diabetes mellitus and health-related quality of life (HRQOL) controlled for several sociodemographic and anthropometric variables, in a representative sample of the Spanish population. Methods. A population-based, cross-sectional, and cluster sampling study, with the entire Spanish population as the target population. Five thousand and forty-seven participants (2162/2885 men/women) answered the HRQOL short form 12-questionnaire (SF-12). The physical (PCS-12) and the mental component summary (MCS-12) scores were assessed. Subjects were divided into four groups according to carbohydrate metabolism status: normal, prediabetes, unknown diabetes (UNKDM), and known diabetes (KDM). Logistic regression analyses were conducted. Results. Mean PCS-12/MCS-12 values were 50.9 ± 8.5/ 47.6 ± 10.2, respectively. Men had higher scores than women in both PCS-12 (51.8 ± 7.2 versus 50.3 ± 9.2; P < 0.001) and MCS-12 (50.2 ± 8.5 versus 45.5 ± 10.8; P < 0.001). Increasing age and obesity were associated with a poorer PCS-12 score. In women lower PCS-12 and MCS-12 scores were associated with a higher level of glucose metabolism abnormality (prediabetes and diabetes), (P < 0.0001 for trend), but only the PCS-12 score was associated with altered glucose levels in men (P < 0.001 for trend). The Odds Ratio adjusted for age, body mass index (BMI) and educational level, for a PCS-12 score below the median was 1.62 (CI 95%: 1.2-2.19; P < 0.002) for men with KDM and 1.75 for women with KDM (CI 95%: 1.26-2.43; P < 0.001), respectively. Conclusion. Current study indicates that increasing levels of altered carbohydrate metabolism are accompanied by a trend towards decreasing quality of life, mainly in women, in a representative sample of Spanish population.

10.1155/2012/872305, Objective. To evaluate the association between diabetes mellitus and health-related quality of life (HRQOL) controlled for several sociodemographic and anthropometric variables, in a representative sample of the Spanish population. Methods. A population-based, cross-sectional, and cluster sampling study, with the entire Spanish population as the target population. Five thousand and forty-seven participants (2162/2885 men/women) answered the HRQOL short form 12-questionnaire (SF-12). The physical (PCS-12) and the mental component summary (MCS-12) scores were assessed. Subjects were divided into four groups according to carbohydrate metabolism status: normal, prediabetes, unknown diabetes (UNKDM), and known diabetes (KDM). Logistic regression analyses were conducted. Results. Mean PCS-12/MCS-12 values were /, respectively. Men had higher scores than women in both PCS-12 ( versus ; ) and MCS-12 ( versus ; ). Increasing age and obesity were associated with a poorer PCS-12 score. In women lower PCS-12 and MCS-12 scores were associated with a higher level of glucose metabolism abnormality (prediabetes and diabetes), ( for trend), but only the PCS-12 score was associated with altered glucose levels in men ( for trend). The Odds Ratio adjusted for age, body mass index (BMI) and educational level, for a PCS-12 score below the median was 1.62 (CI 95%: 1.2–2.19; ) for men with KDM and 1.75 for women with KDM (CI 95%: 1.26–2.43; ), respectively. Conclusion. Current study indicates that increasing levels of altered carbohydrate metabolism are accompanied by a trend towards decreasing quality of life, mainly in women, in a representative sample of Spanish population.