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Role of Advanced Glycation End Products as New Biomarkers in Systemic Lupus Erythematosus.
Carrión-Barberà, I, Triginer, L, Tío, L, Pérez-García, C, Ribes, A, Abad, V, Pros, A, Bermúdez-López, M, Castro-Boqué, E, Lecube, A, et al
International journal of molecular sciences. 2024;(5)
Abstract
Advanced glycation end-products (AGEs) may play a relevant role as inducers in the chronic inflammatory pathway present in immune-mediated diseases, such as systemic lupus erythematosus (SLE). AGEs concentrations have been associated, with discrepant results to date, with some parameters such as disease activity or accrual damage, suggesting their potential usefulness as biomarkers of the disease. Our objectives are to confirm differences in AGEs levels measured by cutaneous autofluorescence between SLE patients and healthy controls (HC) and to study their correlation with various disease parameters. Cross-sectional study, where AGEs levels were measured by skin autofluorescence, and SLE patients' data were compared with those of sex- and age-matched HC in a 1:3 proportion through a multiple linear regression model. Associations of AGEs levels with demographic and clinical data were analyzed through ANOVA tests. Both analyses were adjusted for confounders. AGEs levels in SLE patients were significantly higher than in HC (p < 0.001). We found statistically significant positive associations with SLE disease activity index (SLEDAI) and damage index (SDI), physician and patient global assessment, C-reactive protein, leukocyturia, complement C4, IL-6 and oral ulcers. We also found a negative statistically significant association with current positivity of anti-nuclear and anti-Ro60 antibodies. AGEs seem to have a contribution in LES pathophysiology, being associated with activity and damage and having a role as a new management and prognosis biomarker in this disease. The association with specific antibodies and disease manifestations may indicate a specific clinical phenotype related to higher or lower AGEs levels.
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Association between adherence to the mediterranean diet, physical activity, and sleep apnea-hypopnea syndrome (SAHS) in a middle-aged population with cardiovascular risk: Insights from the ILERVAS cohort.
Salinas-Roca, B, Sánchez, E, Bermúdez-López, M, Valdivielso, JM, Farràs-Sallés, C, Pamplona, R, Torres, G, Mauricio, D, Castro, E, Fernández, E, et al
Sleep medicine. 2024;:19-26
Abstract
INTRODUCTION Sleep Apnea-Hypopnea Syndrome (SAHS) is a common sleep disorder influenced by factors like age, gender, and obesity. The Mediterranean Diet (MedDiet) and physical activity have shown health benefits in lung diseases, but their effects on SAHS remain underexplored. METHODS In a cross-sectional analysis of 678 middle-aged individuals with low-to-moderate cardiovascular risk from the ILERVAS cohort, we assessed adherence to the MedDiet and physical activity levels using validated tools. Sleep parameters, SAHS severity, and excessive daytime sleepiness were evaluated through non-attended cardiorespiratory polygraphy and the Epworth Sleepiness Scale. Multinomial logistic regression models were employed to assess the relationship between MedDiet adherence, physical activity, and SAHS severity. RESULTS The prevalence of severe, moderate, and mild SAHS was 15.5%, 23.2% and 36.1%, respectively. We found no significant associations between adherence to the MedDiet, physical activity levels, and the presence or severity of SAHS. However, we noted a significant interaction between MedDiet and physical activity with minimum SpO2 values (p = 0.049). Notably, consuming more than one serving of red meat per day was independently associated with a higher risk of moderate SAHS [OR = 2.65 (1.29-5.44), p = 0.008]. CONCLUSION Individually, MedDiet adherence and physical activity did not show independent correlations with SAHS. However, when considered together, a minimal but significant effect on minimum SpO2 was observed. Additionally, red meat consumption was associated with a moderate risk of SAHS. Further research is necessary to comprehend the intricate connections between lifestyle factors and sleep-breathing disorders, with a focus on personalized approaches for high-risk populations.
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Low adherence to the Mediterranean diet is associated with increased prevalence and number of atherosclerotic plaques in the ILERVAS cohort.
Rojo-López, MI, Bermúdez-López, M, Castro, E, Farràs, C, Torres, G, Pamplona, R, Lecube, A, Valdivielso, JM, Fernández, E, Julve, J, et al
Atherosclerosis. 2023;:117191
Abstract
BACKGROUND AND AIMS Current research on the association between dietary patterns and subclinical atherosclerotic disease (SAD) is still limited, and published results are inconsistent and often consist of small population sizes. We aimed to evaluate the association between the Mediterranean diet (MDiet) and SAD in a large cohort of Mediterranean individuals. METHODS This was a cross-sectional study that included 8116 subjects from the ILERVAS cohort. The presence of atherosclerotic plaques (AP) was assessed by ultrasound examination. Adherence to the MDiet was assessed using the 14-item Mediterranean Diet Adherence Score (MEDAS). Inclusion criteria were subjects with at least one cardiovascular risk factor. Exclusion criteria were a clinical history of diabetes, chronic kidney disease, or a prior cardiovascular event. Bivariable and multivariable models were performed. RESULTS Compared with subjects without SAD, participants with SAD were older and had a higher frequency of smoking habit, hypertension, dyslipidemia, HbA1c and waist circumference. The adjusted multivariable analysis showed that a higher MEDAS was associated with a lower risk of AP (incidence rate ratios [IRR] 0.97, 95% CI [0.96-0.98]; p<0.001). Furthermore, moderate or high adherence to the MDiet was associated with a lower number of AP compared with a low MDiet adherence (IRR 0.90, 95% CI [0.87-0.94]; p<0.001). In both models, female sex was associated with a lower risk of AP. CONCLUSIONS Our findings point to a potentially protective role of MDiet for SAD in a Mediterranean population with low-to-moderate cardiovascular risk. Further research is needed to establish a causal relationship between both variables.
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Cumulative tobacco consumption has a dose-dependent effect on atheromatosis burden and improves severe atheromatosis prediction in asymptomatic middle-aged individuals: The ILERVAS study.
Bermúdez-López, M, Martí-Antonio, M, Castro-Boqué, E, Bretones, MDM, Farràs, C, Gonzalez, J, Pamplona, R, Lecube, A, Mauricio, D, Cambray, S, et al
Atherosclerosis. 2023;:75-83
Abstract
BACKGROUND AND AIMS Sex-specific impact of cumulative tobacco consumption (CTC) on atheromatosis extension and total plaque area remains unknown. We aimed to determine the impact of CTC in atheromatosis localization and burden. METHODS We performed a cross-sectional analysis in 8330 asymptomatic middle-aged individuals. 12-territory vascular ultrasounds in carotid and femoral arteries were performed to detect atheromatous plaque presence and to measure total plaque area. Adjusted regressions and conditional predictions by smoking habit or CTC (stratified in terciles as low (≤13.53), medium (13.54-29.3), and high (>29.3 packs-year)) were calculated. Severe atheromatosis (SA, ≥3 territories with atheroma plaque) was predicted with the Systematic COronary Risk Evaluation 2 (SCORE2) model. The improvement of SA prediction after adding CTC was evaluated. RESULTS CTC was associated with an increased risk of atheromatosis, stronger in femoral than in carotid artery, but similar in both sexes. A dose-dependent effect of CTC on the number of territories with atheroma plaque and total plaque area was observed. Addition of CTC to the SCORE2 showed a higher sensitivity, accuracy, and negative predictive value in males, and a higher specificity and positive predictive value in females. In both sexes, the new SCORE2-CTC model showed a significant increase in AUC (males: 0.033, females: 0.038), and in the integrated discrimination index (males: 0.072; females: 0.058, p < 0.001). Age and CTC were the most important clinical predictors of SA in both sexes. CONCLUSIONS CTC shows a dose-dependent association with atheromatosis burden, impacts more strongly in femoral arteries, and improves SA prediction.
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Liraglutide Improves Forced Vital Capacity in Individuals With Type 2 Diabetes: Data From the Randomized Crossover LIRALUNG Study.
López-Cano, C, Ciudin, A, Sánchez, E, Tinahones, FJ, Barbé, F, Dalmases, M, García-Ramírez, M, Soto, A, Gaeta, AM, Pellitero, S, et al
Diabetes. 2022;(2):315-320
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Abstract
To evaluate the effect of liraglutide, a glucagon-like peptide 1 receptor agonist, on pulmonary function and serum levels of surfactant protein D (SP-D) in type 2 diabetes. A double-blind, randomized, crossover, placebo-controlled clinical trial comprising 76 patients with a baseline forced expiratory volume in 1 s <90% of that predicted. Liraglutide was administered for 7 weeks (2 weeks of titration plus 5 weeks at 1.8 mg daily). This short duration was intentional to minimize weight loss as a potential confounding factor. Serum level of SP-D was used as a biomarker of alveolar-capillary barrier integrity. Liraglutide exerted a positive impact on forced vital capacity (FVC) in comparison with placebo (ΔFVC 5.2% of predicted [from 0.8 to 9.6]; P = 0.009). No differences in the other pulmonary variables were observed. Participants under liraglutide treatment also experienced a decrease in serum SP-D (P = 0.038). The absolute change in FVC correlated with final serum SP-D in participants receiving liraglutide (r = -0.313, P = 0.036). Stepwise multivariate regression analysis showed that final serum SP-D independently predicted changes in FVC. In conclusion, liraglutide increased FVC in patients with type 2 diabetes. This effect was associated with a significant decrease of circulating SP-D, thus pointing to a beneficial effect in the alveolar-capillary function.
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Weak Association between Skin Autofluorescence Levels and Prediabetes with an ILERVAS Cross-Sectional Study.
Sánchez, E, Kerkeni, M, Hernández, M, Gavaldà, R, Rius, F, Sauret, A, Torres, G, Bermúdez-López, M, Fernández, E, Castro-Boqué, E, et al
Nutrients. 2022;(5)
Abstract
A large body of evidence demonstrates a relationship between hyperglycemia and increased concentrations of advanced glycation end-products (AGEs). However, there is little information about subcutaneous AGE accumulation in subjects with prediabetes, and whether or not this measurement could assist in the diagnosis of prediabetes is unclear. A cross-sectional study was conducted in 4181 middle-aged subjects without diabetes. Prediabetes (n = 1444) was defined as a glycosylated hemoglobin (HbA1c) level between 39 and 47 mmol/mol (5.7 to 6.4%), and skin autofluorescence (SAF) measurement was performed to assess AGEs. A multivariable logistic regression model and receiver operating characteristic curve were used. The cohort consisted of 50.1% women with an age of 57 [52;62] years, a BMI of 28.3 [25.4;31.6] kg/m2, and a prevalence of prediabetes of 34.5%. Participants with prediabetes showed higher SAF than control participants (2.0 [1.7;2.2] vs. 1.9 [1.7;2.2], p < 0.001). However, HbA1c was not significantly correlated with SAF levels (r = 0.026, p = 0.090). In addition, the SAF level was not independently associated with prediabetes (OR = 1.12 (0.96 to 1.30)). Finally, there was no good cutoff point for SAF to identify patients with prediabetes (AUC = 0.52 (0.50 to 0.54), sensitivity = 0.61, and 1-specificity = 0.56). Given all of this evidence, we can conclude that although there is an increase in SAF levels in participants with prediabetes, the applicability and clinical relevance of the results is low in this population.
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Is There a Link between Obesity Indices and Skin Autofluorescence? A Response from the ILERVAS Project.
Sánchez, E, Sánchez, M, López-Cano, C, Bermúdez-López, M, Valdivielso, JM, Farràs-Sallés, C, Pamplona, R, Torres, G, Mauricio, D, Castro, E, et al
Nutrients. 2022;(1)
Abstract
There is controversial information about the accumulation of advanced glycation end-products (AGEs) in obesity. We assessed the impact of total and abdominal adiposity on AGE levels via a cross-sectional investigation with 4254 middle-aged subjects from the ILERVAS project. Skin autofluorescence (SAF), a non-invasive assessment of subcutaneous AGEs, was measured. Total adiposity indices (BMI and Clínica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE)) and abdominal adiposity (waist circumference and body roundness index (BRI)) were assessed. Lean mass was estimated using the Hume index. The area under the receiver operating characteristic (ROC) curve was evaluated for each index. Different cardiovascular risk factors (smoking, prediabetes, hypertension and dyslipidemia) were evaluated. In the study population, 26.2% showed elevated SAF values. No differences in total body fat, visceral adiposity and lean body mass were detected between patients with normal and high SAF values. SAF levels showed a very slight but positive correlation with total body fat percentage (estimated by the CUN-BAE formula) and abdominal adiposity (estimated by the BRI). However, none of them had sufficient power to identify patients with high SAF levels (area under the ROC curve <0.52 in all cases). Finally, a progressive increase in SAF levels was observed in parallel with cardiovascular risk factors in the entire population and when patients with normal weight, overweight and obesity were evaluated separately. In conclusion, total obesity and visceral adiposity are not associated with a greater deposit of AGE. The elevation of AGE in obesity is related to the presence of cardiometabolic risk.
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Development and Validation of a Personalized, Sex-Specific Prediction Algorithm of Severe Atheromatosis in Middle-Aged Asymptomatic Individuals: The ILERVAS Study.
Bermúdez-López, M, Martí-Antonio, M, Castro-Boqué, E, Bretones, MDM, Farràs, C, Torres, G, Pamplona, R, Lecube, A, Mauricio, D, Valdivielso, JM, et al
Frontiers in cardiovascular medicine. 2022;:895917
Abstract
BACKGROUND Although European guidelines recommend vascular ultrasound for the assessment of cardiovascular risk in low-to-moderate risk individuals, no algorithm properly identifies patients who could benefit from it. The aim of this study is to develop a sex-specific algorithm to identify those patients, especially women who are usually underdiagnosed. METHODS Clinical, anthropometrical, and biochemical data were combined with a 12-territory vascular ultrasound to predict severe atheromatosis (SA: ≥ 3 territories with plaque). A Personalized Algorithm for Severe Atheromatosis Prediction (PASAP-ILERVAS) was obtained by machine learning. Models were trained in the ILERVAS cohort (n = 8,330; 51% women) and validated in the control subpopulation of the NEFRONA cohort (n = 559; 47% women). Performance was compared to the Systematic COronary Risk Evaluation (SCORE) model. RESULTS The PASAP-ILERVAS is a sex-specific, easy-to-interpret predictive model that stratifies individuals according to their risk of SA in low, intermediate, or high risk. New clinical predictors beyond traditional factors were uncovered. In low- and high-risk (L&H-risk) men, the net reclassification index (NRI) was 0.044 (95% CI: 0.020-0.068), and the integrated discrimination index (IDI) was 0.038 (95% CI: 0.029-0.048) compared to the SCORE. In L&H-risk women, PASAP-ILERVAS showed a significant increase in the area under the curve (AUC, 0.074 (95% CI: 0.062-0.087), p-value: < 0.001), an NRI of 0.193 (95% CI: 0.162-0.224), and an IDI of 0.119 (95% CI: 0.109-0.129). CONCLUSION The PASAP-ILERVAS improves SA prediction, especially in women. Thus, it could reduce the number of unnecessary complementary explorations selecting patients for a further imaging study within the intermediate risk group, increasing cost-effectiveness and optimizing health resources. CLINICAL TRIAL REGISTRATION [www.ClinicalTrials.gov], identifier [NCT03228459].
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Recommendations for the diagnosis and treatment of hypoglycaemia after bariatric surgery.
Vilarrasa, N, Bretón, I, Ballesteros-Pomar, M, Lecube, A, Goday, A, Pellitero, S, Sánchez, R, Zugasti, A, Ciudin, A, de Hollanda, A, et al
Endocrinologia, diabetes y nutricion. 2022;(9):723-731
Abstract
Postprandial hyperinsulinaemic hypoglycaemia is a common complication of bariatric surgery. Although in general its evolution is mild and self-limited, it can lead to neuroglycopaenia and compromise the patient's safety and quality of life. The aim of this document is to offer some recommendations to facilitate the clinical care of these complex patients, reviewing the aetiopathogenesis, its diagnosis and treatment that, sequentially, will include dietary and pharmacological measures and surgery in refractory cases. In the absence of high-quality studies, the diagnostic and therapeutic approach proposed is based on the consensus of experts of the Grupo de Obesidad de la Sociedad Española de Endocrinología y Nutrición [Obesity Group of the Spanish Society of Endocrinology and Nutrition], GOSEEN. Those undergoing bariatric surgery should be informed of the possibility of developing this complication.
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Prediabetes Is Associated with Increased Prevalence of Sleep-Disordered Breathing.
Sánchez, E, Sapiña-Beltrán, E, Gavaldà, R, Barbé, F, Torres, G, Sauret, A, Dalmases, M, López-Cano, C, Gutiérrez-Carrasquilla, L, Bermúdez-López, M, et al
Journal of clinical medicine. 2022;(5)
Abstract
Type 2 diabetes leads to severe nocturnal hypoxemia, with an increase in apnea events and daytime sleepiness. Hence, we assessed sleep breathing parameters in the prediabetes stage. A cross-sectional study conducted on 966 middle-aged subjects without known pulmonary disease (311 patients with prediabetes and 655 controls with normal glucose metabolism) was conducted. Prediabetes was defined by glycated hemoglobin (HbA1c), and a nonattended overnight home sleep study was performed. Participants with prediabetes (n = 311) displayed a higher apnea−hypopnea index (AHI: 12.7 (6.1;24.3) vs. 9.5 (4.2;19.6) events/h, p < 0.001) and hypopnea index (HI: 8.4 (4.0;14.9) vs. 6.0 (2.7;12.6) events/h, p < 0.001) than controls, without differences in the apnea index. Altogether, the prevalence of obstructive sleep apnea was higher in subjects with prediabetes than in controls (78.1 vs. 69.9%, p = 0.007). Additionally, subjects with prediabetes presented impaired measurements of the median and minimum nocturnal oxygen saturation, the percentage of time spent with oxygen saturations below 90%, and the 4% oxygen desaturation index in comparison with individuals without prediabetes (p < 0.001 for all). After adjusting for age, sex, and the presence of obesity, HbA1c correlated with the HI in the entire population (r = 0.141, p < 0.001), and the presence of prediabetes was independently associated with the AHI (B = 2.20 (0.10 to 4.31), p = 0.040) as well as the HI (B = 1.87 (0.61 to 3.14), p = 0.004) in the multiple linear regression model. We conclude that prediabetes is an independent risk factor for an increased AHI after adjusting for age, sex, and obesity. The enhanced AHI is mainly associated with increments in the hypopnea events.