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Objective:Thyroid hormone receptor-beta resistance has been associated with metabolic traits. THRA gene sequencing of an obese woman (index case) who presented as empirical thyroid hormone receptor-α (THRA) resistance, disclosed a polymorphism (rs12939700) in a critical region involved in TRα alternative processing.Design and subjects:THRA gene variants were evaluated in three independent europid populations (i) in two population cohorts at baseline (n=3417 and n=2265), 6 years later (n=2139) and (ii) in 4734 high cardiovascular risk subjects (HCVR, PREDIMED trial).Results:The minor allele of the index case polymorphism (rs12939700), despite having a very low frequency (4%), was significantly associated with higher body mass index (BMI) (P=0.042) in HCVR subjects. A more frequent THRA polymorphism (rs1568400) was associated with higher BMI in subjects from the population (P=0.00008 and P=0.05) after adjusting for several confounders. Rs1568400 was also strongly associated with fasting triglycerides (P dominant=3.99 × 10−5). In the same sample, 6 years later, age and sex-adjusted risk of developing obesity was significantly increased in GG homozygotes (odds ratio 2.93 (95% confidence interval, 1.05-6.95)). In contrast, no association between rs1568400 and BMI was observed in HCVR subjects, in whom obesity was highly prevalent. This might be explained by the presence of an interaction (P <0.001) among the rs1568400 variant, BMI and saturated fat intake. Only when saturated fat intake was high (>24.5 g d−1), GG carriers showed a significantly higher BMI than A carriers after controlling for energy intake and physical activity.Conclusions:THRA gene polymorphisms are associated with obesity development. This is a novel observation linking the THRA locus to metabolic phenotypes. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the cross-sectional association between severe periodontitis and diabetes mellitus (DM), in a representative sample of Spanish population., Materials and Methods: The di@bet.es epidemiological study is a population-based cohort study aimed to determine the prevalence and incidence of DM in the adult population of Spain. The at-risk sample at the final examination (2016-2017) included 1751 subjects who completed an oral health questionnaire. This questionnaire, together with demographic and risk factors, had been previously validated to build an algorithm to predict severe periodontitis in the Spanish population. Logistic regression models were used to evaluate the association between severe periodontitis and DM with adjustment for confounding factors., Results: In total, 144 subjects developed DM, which yielded 8.2% cumulative incidence. Severe periodontitis was detected in 59.0%, 54.7% or 68.8% of the subjects depending on three different selected criteria at the 2016-2017 exam. All criteria used to define severe periodontitis were associated with DM in unadjusted analysis, but the magnitude of the association decreased after adjusting for significant confounders. The criteria '≥50% of teeth with clinical attachment loss ≥5 mm' presented an odds ratio of 4.9 (95% confidence interval: 2.2-10.7; p ≤ .001) for DM., Conclusions: Severe periodontitis is associated with DM in the Spanish population., (© 2023 The Authors. Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

Background and Aims: We aimed to assess the associations of exposure to air pollutants and standard and advanced lipoprotein measures, in a nationwide sample representative of the adult population of Spain., Methods: We included 4647 adults (>18 years), participants in the national, cross-sectional, population-based di@bet.es study, conducted in 2008-2010. Standard lipid measurements were analysed on an Architect C8000 Analyzer (Abbott Laboratories SA). Lipoprotein analysis was made by an advanced 1 H-NMR lipoprotein test (Liposcale®). Participants were assigned air pollution concentrations for particulate matter <10 μm (PM 10 ), <2.5 μm (PM 2.5 ) and nitrogen dioxide (NO 2 ), corresponding to the health examination year, obtained by modelling combined with measurements taken at air quality stations (CHIMERE chemistry-transport model)., Results: In multivariate linear regression models, each IQR increase in PM 10 , PM 2.5 and NO 2 was associated with 3.3%, 3.3% and 3% lower levels of HDL-c and 1.3%, 1.4% and 1.1% lower HDL particle (HDL-p) concentrations (p < .001 for all associations). In multivariate logistic regression, there was a significant association between PM 10 , PM 2.5 and NO 2 concentrations and the odds of presenting low HDL-c (<40 mg/dL), low HDL-p (10 and NO 2 and low HDL-p in men (p for interaction .008 and .034), and between NO 2 and low HDL-p in individuals with obesity (p for interaction .015)., Conclusions: Our study shows an association between the exposure to air pollutants and blood lipids in the general population of Spain, suggesting a link to atherosclerosis., (© 2023 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

The progression of obesity and type 2 diabetes (T2D) is intricately linked with adipose tissue (AT) angiogenesis. Despite an established network of microRNAs (miRNAs) regulating AT function, the specific role of angiogenic miRNAs remains less understood. The miR-221/222 cluster has recently emerged as being associated with antiangiogenic activity. However, no studies have explored its role in human AT amidst the concurrent development of obesity and T2D. Therefore, this study aims to investigate the association between the miR-221-3p/222-3p cluster in human AT and its regulatory network with obesity and T2D. MiR-221-3p/222-3p and their target gene (TG) expression levels were quantified through qPCR in visceral (VAT) and subcutaneous (SAT) AT from patients ( n = 33) categorized based on BMI as normoweight (NW) and obese (OB) and by glycemic status as normoglycemic (NG) and type 2 diabetic (T2D) subjects. In silico analyses of miR-221-3p/222-3p and their TGs were conducted to identify pertinent signaling pathways. The results of a multivariate analysis, considering the simultaneous expression of miR-221-3p and miR-222-3p as dependent variables, revealed statistically significant distinctions when accounting for variables such as tissue depot, obesity, sex, and T2D as independent factors. Furthermore, both miRNAs and their TGs exhibited differential expression patterns based on obesity severity, glycemic status, sex, and type of AT depot. Our in silico analysis indicated that miR-221-3p/222-3p cluster TGs predominantly participate in angiogenesis, WNT signaling, and apoptosis pathways. In conclusion, these findings underscore a promising avenue for future research, emphasizing the miR-221-3p/222-3p cluster and its associated regulatory networks as potential targets for addressing obesity and related metabolic disorders.

Introduction: The quality of diabetes care varies from region to region. The objective of this study is to analyze the characteristics of care in different hospitals in Spain through a specific survey assessing different aspects of care for both children and adults., Materials and Methods: Cross-sectional observational voluntary survey study, sent to the heads of the Endocrinology and Pediatric Endocrinology Departments or Units in public hospitals with more than 150 beds, during the first semester of 2021. A total of 105 responses were obtained, 55.5% of the 189 requested, which corresponded to a population served of 31,782,409 people, representing almost 80% of the total population served., Results: Patients with diabetes under 15 years of age are cared for by Pediatric Departments, but only 58% of them have a specific Diabetes Education Unit for children, and in 72% of the cases, there is one single nurse dedicated to these tasks, and not always full-time. Those over 15 years of age are attended by specialists in Endocrinology and Nutrition in 94.3 % of hospitals. There are Therapeutic Education Units in Diabetes in practically all hospitals (94.3%). However, Diabetes Day Hospitals exist in only 32 centres and cover 40.3% of the population, since in 22 provinces there are none. Virtual and telematic consultations, as well as retinography, are available in more than 70% of cases, but access to a Diabetic Foot Unit only in 54% of centres. Monographic technological consultations on diabetes have become widespread, but access to mental health specialists with diabetes training remains limited (24% of centres), and interdisciplinary (32%) or interlevel (12%) committees are very scarce., Conclusion: Diabetes care in Spain shows great variability from one region to another, and some deficiencies have been detected that affect a large part of the population, such as access to Diabetic Foot Units, as well as mental health specialists with specific training. The presence of multidisciplinary and mixed committees between levels of care remains scarce., (Copyright © 2023 SEEN and SED. Published by Elsevier España, S.L.U. All rights reserved.)

Aims: 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., Methods: 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., Results: 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., Conclusions: 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., Competing Interests: Declaration of Competing Interest N.A. is stock owner of Biosfer Teslab and has a patent on the method for lipoprotein profiling described in the present manuscript. E.O. was employed at Biosfer Teslab. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Oleocanthal and oleacein are olive oil phenolic compounds with well known anti-inflammatory and anti-oxidant properties. The main evidence, however, is provided by experimental studies. Few human studies have examined the health benefits of olive oils rich in these biophenols. Our aim was to assess the health properties of rich oleocanthal and oleacein extra virgin olive oil (EVOO), compared to those of common olive oil (OO), in people with prediabetes and obesity., Methods: Randomised, double-blind, crossover trial done in people aged 40-65 years with obesity (BMI 30-40 kg/m 2 ) and prediabetes (HbA1c 5.7-6.4%). The intervention consisted in substituting for 1 month the oil used for food, both raw and cooked, by EVOO or OO. No changes in diet or physical activity were recommended. The primary outcome was the inflammatory status. Secondary outcomes were the oxidative status, body weight, glucose handling and lipid profile. An ANCOVA model adjusted for age, sex and treatment administration sequence was used for the statistical analysis., Results: A total of 91 patients were enrolled (33 men and 58 women) and finished the trial. A decrease in interferon-γ was observed after EVOO treatment, reaching inter-treatment differences (P = 0.041). Total antioxidant status increased and lipid and organic peroxides decreased after EVOO treatment, the changes reaching significance compared to OO treatment (P < 0.05). Decreases in weight, BMI and blood glucose (p < 0.05) were found after treatment with EVOO and not with OO., Conclusions: Treatment with EVOO rich in oleocanthal and oleacein differentially improved oxidative and inflammatory status in people with obesity and prediabetes., Competing Interests: Conflict of interest The authors have no conflicts of interest to declare for this study. All co-authors have seen and agree with the contents of the manuscript and there is no financial interest to report. Cortijo Suerte Alta S.L. (Albendín, Baena, Córdoba, Spain) and Jacoliva S.L. (Pozuelo de Zarzón, Cáceres, Spain) supplied for free the olive oils but had no role in the analysis and interpretation of the data as well as in the decision to publish the findings., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aims: To compare efficacy and safety of degludec 100 IU/mL (Deg-100) and glargine 300 IU/mL (Gla-300) in adults with type 1 diabetes., Methods: Open-label, single-center, randomized, parallel-group, 24-week trial in adults with type 1 diabetes, on basal-bolus insulin therapy, HbA1c ≤ 10%, using self-monitoring blood glucose. Participants were randomized 1:1 to a basal-bolus insulin regimen with Deg-100 (N = 129) or Gla-300 (N = 131). Primary efficacy endpoint: mean change in HbA1c from baseline to week-24. Main safety outcome: incidence rate of hypoglycemia during the study. Quality of life (DQOL) and satisfaction with diabetes treatment (DTSQ) were assessed., Results: At week 24, after adjusting for baseline HbA1c, the decrease in HbA1c did not differ between groups: Deg-100 (-0.07 ± 0.7%) and Gla-300 (-0.16 ± 0.77%) (P = 0.320). There were no significant differences between groups in HbA1c, nocturnal hypoglycemia, severe hypoglycemia, DQOL, or DTSQ scores. The incidence rates of hypoglycemia < 3.9 mmol/L (Deg-100: 115.24 events/person-year vs Gla-300: 99.01 events/person-year, p < 0.001); and < 3.0 mmol/L (Deg-100: 41.17 events/person-year vs Gla-300: 34.29 events/person-year, p < 0.001) were different between groups., Conclusions: Deg-100 and Gla-300 have similar metabolic efficacy, incidence ratio of nocturnal and severe hypoglycemia, DQOL and DTSQ scores. Differences in the incidence rate of hypoglycemia < 3.9 mmol/L and < 3.0 mmol/L should be confirmed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background/objectives: Although vascular endothelial growth factor b (VEGFb) might have an impact on the development of obesity, diabetes and related disorders, the possible relationship between VEGFb serum levels and the incidence of these metabolic complications in humans is still unknown. The aim of our study was to evaluate the association between VEGFb serum levels and the new-onset of metabolic syndrome (MS) and its components in the Spanish adult population after 7.5 years of follow-up., Subjects/methods: A total of 908 subjects from the Di@bet.es cohort study without MS at cross-sectional stage according to International Diabetes Federation (IDF) or Adult Treatment Panel III (ATP-III) criteria were included. Additionally, five sub-populations were grouped according to the absence of each MS component at baseline. Socio-demographic, anthropometric and clinical data were recorded. The Short Form of International Physical Activity Questionnaire (SF-IPAQ) was used to estimate physical activity. A fasting blood extraction and an oral glucose tolerance test were performed. Serum determinations of glucose, lipids, hsCRP and insulin were made. VEGFb levels were determined and categorized according to the 75th percentile of the variable. New cases of MS and its components were defined according to ATPIII and IDF criteria., Results: A total of 181 or 146 people developed MS defined by IDF or ATP-III criteria respectively. Serum triglyceride levels, hs-CRP and systolic blood pressure at the baseline study were significantly different according to the VEGFb categories. Adjusted logistic regression analysis showed that the likelihood of developing MS and abdominal obesity was statistically reduced in subjects included in the higher VEGFb category., Conclusion: Low serum levels of VEGFb may be considered as early indicators of incident MS and abdominal obesity in the Spanish adult population free of MS, independently of other important predictor variables., (© 2022. The Author(s).)

Background: Recent reports have suggested that air pollution may impact thyroid function, although the evidence is still scarce and inconclusive. In this study we evaluated the association of exposure to air pollutants to thyroid function parameters in a nationwide sample representative of the adult population of Spain., Methods: The Di@bet.es study is a national, cross-sectional, population-based survey which was conducted in 2008-2010 using a random cluster sampling of the Spanish population. The present analyses included 3859 individuals, without a previous thyroid disease diagnosis, and with negative thyroid peroxidase antibodies (TPO Abs) and thyroid-stimulating hormone (TSH) levels of 0.1-20 mIU/L. Participants were assigned air pollution concentrations for particulate matter <2.5μm (PM 2.5 ) and Nitrogen Dioxide (NO 2 ), corresponding to the health examination year, obtained by means of modeling combined with measurements taken at air quality stations (CHIMERE chemistry-transport model). TSH, free thyroxine (FT4), free triiodothyronine (FT3) and TPO Abs concentrations were analyzed using an electrochemiluminescence immunoassay (Modular Analytics E170 Roche)., Results: In multivariate linear regression models, there was a highly significant negative correlation between PM 2.5 concentrations and both FT4 (p<0.001), and FT3 levels (p<0.001). In multivariate logistic regression, there was a significant association between PM 2.5 concentrations and the odds of presenting high TSH [OR 1.24 (1.01-1.52) p=0.043], lower FT4 [OR 1.25 (1.02-1.54) p=0.032] and low FT3 levels [1.48 (1.19-1.84) p=<0.001] per each IQR increase in PM 2.5 (4.86 μg/m 3 ). There was no association between NO 2 concentrations and thyroid hormone levels. No significant heterogeneity was seen in the results between groups of men, pre-menopausal and post-menopausal women., Conclusions: Exposures to PM 2.5 in the general population were associated with mild alterations in thyroid function., (© 2022. The Author(s).)

The purpose of this study was to identify clinical, analytical, and sociodemographic variables associated with the need for hospital admission in people over 50 years infected with SARS-CoV-2 and to assess whether diabetes mellitus conditions the risk of hospitalization. A multicenter case-control study analyzing electronic medical records in patients with COVID-19 from 1 March 2020 to 30 April 2021 was conducted. We included 790 patients: 295 cases admitted to the hospital and 495 controls. Under half ( n = 386, 48.8%) were women, and 8.5% were active smokers. The main comorbidities were hypertension (50.5%), dyslipidemia, obesity, and diabetes (37.5%). Multivariable logistic regression showed that hospital admission was associated with age above 65 years (OR from 2.45 to 3.89, ascending with age group); male sex (OR 2.15, 95% CI 1.47-3.15), fever (OR 4.31, 95% CI 2.87-6.47), cough (OR 1.89, 95% CI 1.28-2.80), asthenia/malaise (OR 2.04, 95% CI 1.38-3.03), dyspnea (4.69, 95% CI 3.00-7.33), confusion (OR 8.87, 95% CI 1.68-46.78), and a history of hypertension (OR 1.61, 95% CI 1.08-2.41) or immunosuppression (OR 4.97, 95% CI 1.45-17.09). Diabetes was not associated with increased risk of hospital admission (OR 1.18, 95% CI 0.80-1.72; p = 0.38). Diabetes did not increase the risk of hospital admission in people over 50 years old, but advanced age, male sex, fever, cough, asthenia, dyspnea/confusion, and hypertension or immunosuppression did.

The identification of nutritional patterns associated with the development of type 2 diabetes (T2D) might help lead the way to a more efficient and personalized nutritional intervention. Our study is aimed at evaluating the association between fatty acids (FA) in red blood cell (RBC) membranes, as a quantitative biomarker of regular dietary fat intake, and incident type 2 diabetes in a Spanish population. We included 1032 adult Spaniards (57% women, age 49 ± 15 years, 18% prediabetes), without diabetes at study entry, from the Di@bet.es cohort. Incident diabetes was diagnosed at the end of the study follow-up. The FA percentage in RBC was determined at baseline by gas chromatography. Participants were followed on average 7.5 ± 0.6 years. Lower percentages of linoleic acid (LA), α-linolenic (ALA), and eicosapentaenoic acid (EPA), and higher percentages of docosahexaenoic acid (DHA) in RBC membranes were associated, independently of classical risk factors, with worse glucose metabolism at the end of the study follow-up. In addition, higher percentages of ALA and EPA, and moderate percentages of DHA, were associated with lower risk of diabetes. No significant associations were found for LA and diabetes risk. Dietary patterns rich in vegetables are independently associated with lower risk of both deterioration of glucose regulation and incident diabetes, and should be reinforced for the prevention of diabetes.

Introduction and Objectives: Atherosclerotic cardiovascular disease and heart failure are the leading cause of morbidity and mortality in patients with diabetes. The objective of this work is to know the prevalence of atherosclerotic cardiovascular diseases and heart failure in people diagnosed with diabetes in Spain during 2017 and compare them with those not diagnosed with diabetes according to age and sex., Methods: Data for diagnoses of diabetes mellitus (DM), acute myocardial infarction (AMI), stroke, peripheral artery disease (PAD) or heart failure (HF) for 2017 were obtained from the National Health System's Primary Care Clinical Database (BDCAP)., Results: Comparing people with diabetes and people without diabetes over 35 years of age, the Odds Ratio (OR) for being diagnosed with acute myocardial infarction, stroke, peripheral artery disease or heart failure is about 2 in those over 64 years of age and more than 4 in patients under that age. This OR is superior in females versus males for all diagnoses apart from peripheral artery disease., Conclusions: This study shows the high cardiovascular comorbidity of patients with diabetes in Spain, with a greater excess of risk in patients under 65 years of age, more pronounced in women. We should offer more intensive treatment for DM2 in women., (Copyright © 2021 Elsevier España, S.L.U. All rights reserved.)