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1.
Increasing the complexity of lipoprotein characterization for cardiovascular risk in type 2 diabetes.
Guardiola, M, Rehues, P, Amigó, N, Arrieta, F, Botana, M, Gimeno-Orna, JA, Girona, J, Martínez-Montoro, JI, Ortega, E, Pérez-Pérez, A, et al
European journal of clinical investigation. 2024;:e14214
Abstract
The burden of cardiovascular disease is particularly high among individuals with diabetes, even when LDL cholesterol is normal or within the therapeutic target. Despite this, cholesterol accumulates in their arteries, in part, due to persistent atherogenic dyslipidaemia characterized by elevated triglycerides, remnant cholesterol, smaller LDL particles and reduced HDL cholesterol. The causal link between dyslipidaemia and atherosclerosis in T2DM is complex, and our contention is that a deeper understanding of lipoprotein composition and functionality, the vehicle that delivers cholesterol to the artery, will provide insight for improving our understanding of the hidden cardiovascular risk of diabetes. This narrative review covers three levels of complexity in lipoprotein characterization: 1-the information provided by routine clinical biochemistry, 2-advanced nuclear magnetic resonance (NMR)-based lipoprotein profiling and 3-the identification of minor components or physical properties of lipoproteins that can help explain arterial accumulation in individuals with normal LDLc levels, which is typically the case in individuals with T2DM. This document highlights the importance of incorporating these three layers of lipoprotein-related information into population-based studies on ASCVD in T2DM. Such an attempt should inevitably run in parallel with biotechnological solutions that allow large-scale determination of these sets of methodologically diverse parameters.
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2.
The Consumption of a Synbiotic Does Not Affect the Immune, Inflammatory, and Sympathovagal Parameters in Athletes and Sedentary Individuals: A Triple-Blinded, Randomized, Place-bo-Controlled Pilot Study.
Quero-Calero, CD, Abellán-Aynés, O, Manonelles, P, Ortega, E
International journal of environmental research and public health. 2022;(6)
Abstract
This investigation aimed to identify the effect of a synbiotic in athletes and sedentary people, and their potential varying responses regarding the immune system, autonomic regulation and body composition. Twenty-seven participants were involved in the protocol: 14 sedentary and 13 semi-professional soccer players. Both groups were randomly divided into an experimental and control group. A synbiotic (Gasteel Plus®, Heel España S.A.U.) comprising a blend of probiotic strains, including Bifidobacterium lactis CBP-001010, Lactobacillus rhamnosus CNCM I-4036, and Bifidobacterium longum ES1, was administered to the experimental group, and a placebo was given to the control group for 30 days. Heart rate variability, body composition, and immune/inflammatory cytokines were determined. Statistically significant differences were observed between sedentary individuals and athletes in heart rate variability but not between the experimental and control groups. A difference between the athletic and sedentary group is observed with the influence of training on the effects of the synbiotic on the levels of fat mass and body-fold sum. No significant differences were shown in cytokines after the protocol study. No changes occur with the synbiotic treatment between the athlete and sedentary groups, while no negative effect was produced. Further research will be necessary to see chronic effects in the analyzed biomarkers.
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3.
Compliance with the DPP-4 inhibitors dose adjustment recommendations based on renal function in a population database.
Franch-Nadal, J, Gatius, JR, Mata-Cases, M, Ortega, E, Valles, JA, Vlacho, B, Mauricio, D
Endocrinologia, diabetes y nutricion. 2022;(2):83-91
Abstract
OBJECTIVE To examine the prescription pattern of the different dipeptidyl peptidase-4 inhibitors (DPP4is), depending on the estimated glomerular filtration rate (eGFR) under real-world clinical practice conditions. METHOD This was a descriptive, observational study using a population database (SIDIAP Catalonia). Subjects diagnosed with T2DM with kidney function assessed and on active treatment with DPP4is were enrolled. Patients were included at the time of the measurement of eGFR (CKD-epi) and were monitored for 6 months after enrolment. For each subject, the prescribed daily dose (PDD) of DPP4i, the theoretical dose according to the degree of renal failure established by the recommendations in the summary of product characteristics (DDD-adj), and the PDR ratio (PDD/DDD-adj) were estimated. A subject was considered overtreated if his/her RDR was greater than 1.2 (>20%). RESULTS The study sample consisted of 72,135 subjects with a mean age of 69.7 (±11.6) years and 55.9% males. The proportion of patients overtreated varied depending on the type of DPP4i and the renal function stage. Overall, overdosage was recorded in 7.15% of all DPP4i treatments. In advanced stages (IIIb, IV, and V), overdosage was much higher (36.8% for all DPP4is, and 58.7% if linagliptin is excluded). DISCUSSION Under real-world clinical practice conditions, more than one third of T2DM patients with advanced renal failure were overdosed with DPP4is because the doses were not adequately adjusted to the glomerular filtration rate of each patient.
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4.
Determinants of response to the glucagon-like peptide-1 receptor agonists in a type 2 diabetes population in the real-world.
Franch-Nadal, J, Granado-Casas, M, Mata-Cases, M, Ortega, E, Vlacho, B, Mauricio, D
Primary care diabetes. 2022;(6):810-817
Abstract
AIMS: To identify clinical predictors associated with a response in terms of glycemic control and weight loss in patients with type 2 diabetes treated with glucagon-like peptide-1 receptor agonists (GLP-1RAs). METHODS A retrospective observational study was performed with real-world databases in primary care. Patients with type 2 diabetes-initiated treatment with GLP-1RAs during the study period, and response to GLP-1RAs were determined six months from treatment initiation. An optimal glycated hemoglobin (HbA1c) or weight response was defined as a reduction of ≥ 1% or ≥ 3%, respectively. A "great" response was defined as both an optimal HbA1c and weight response. Bivariate and multivariate analyses with intention-to-treat were performed. RESULTS A sample of 2944 patients with type 2 diabetes was recruited. Higher HbA1c at baseline was the main clinical predictor of an optimal HbA1c response (odds ratio [OR]: 2.30, 95% confidence interval [CI]: 1.96-2.71 in men and OR: 2.03, 95% CI: 1.76-2.33 in women). Treatment without insulin at baseline was associated with a greater weight reduction in men (OR: 2.50, 95% CI: 1.41-4.44). Older age and a higher weight at baseline were related with this in women (OR: 1.02, 95% CI: 1.00-1.05 and OR: 1.01, 95% CI: 1.00-1.02, respectively). CONCLUSIONS A high HbA1c at baseline and previous non-insulin therapy were the main predictors of a greater response (optimal HbA1c and weight response) to GLP1ra in both men and women. This may aid in treatment decision-making before initiating treatment with GLP-1RAs.
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The Influence of Obesity and Weight Loss on the Bioregulation of Innate/Inflammatory Responses: Macrophages and Immunometabolism.
Gálvez, I, Navarro, MC, Martín-Cordero, L, Otero, E, Hinchado, MD, Ortega, E
Nutrients. 2022;(3)
Abstract
Obesity is characterized by low-grade inflammation and more susceptibility to infection, particularly viral infections, as clearly demonstrated in COVID-19. In this context, immunometabolism and metabolic flexibility of macrophages play an important role. Since inflammation is an inherent part of the innate response, strategies for decreasing the inflammatory response must avoid immunocompromise the innate defenses against pathogen challenges. The concept "bioregulation of inflammatory/innate responses" was coined in the context of the effects of exercise on these responses, implying a reduction in excessive inflammatory response, together with the preservation or stimulation of the innate response, with good transitions between pro- and anti-inflammatory macrophages adapted to each individual's inflammatory set-point in inflammatory diseases, particularly in obesity. The question now is whether these responses can be obtained in the context of weight loss by dietary interventions (low-fat diet or abandonment of the high-fat diet) in the absence of exercise, which can be especially relevant for obese individuals with difficulties exercising such as those suffering from persistent COVID-19. Results from recent studies are controversial and do not point to a clear anti-inflammatory effect of these dietary interventions, particularly in the adipose tissue. Further research focusing on the innate response is also necessary.
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Root-System Architectures of Two Cuban Rice Cultivars with Salt Stress at Early Development Stages.
Vázquez-Glaría, A, Eichler-Löbermann, B, Loiret, FG, Ortega, E, Kavka, M
Plants (Basel, Switzerland). 2021;(6)
Abstract
Soil salinity is a critical problem for rice production and is also often associated with phosphors (P) deficiency. Plant hormones, like brassinosteroids, were shown to play a role in plant responses to different stresses and are also expected to mitigate salt stress. The aim of this study was to compare shoot growth and root architecture traits of two rice cultivars (INCA LP-5 and Perla de Cuba) during early plant development in response to salt, P limitation and a brassinosteroid. Seeds were placed in (I) paper rolls for 7 days and (II) mini-rhizotrons for 21 days without or with salt (50 mM NaCl), without or with 24-epibrassinolide (10-6 M) pre-treatment, and with two levels of P (10 or 1 ppm). The root system of LP-5 was larger in size and extent, while the roots of Perla were growing denser. Salt affected mainly the size- and extent-related root characteristics and explained about 70% of the variance. The effect of P was more pronounced without salt treatment. In Perla, P supply reduced the salt effect on root growth. The brassinosteroid had hardly any effect on the development of the plants in both experiments. Due to the high dependence on experimental factors, root length and related traits can be recommended for selecting young rice cultivars regarding salt stress and P deprivation.
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7.
Impact of COVID-19 Lockdown in Eating Disorders: A Multicentre Collaborative International Study.
Baenas, I, Etxandi, M, Munguía, L, Granero, R, Mestre-Bach, G, Sánchez, I, Ortega, E, Andreu, A, Moize, VL, Fernández-Real, JM, et al
Nutrients. 2021;(1)
Abstract
BACKGROUND The COVID-19 lockdown has had a significant impact on mental health. Patients with eating disorders (ED) have been particularly vulnerable. AIMS (1) To explore changes in eating-related symptoms and general psychopathology during lockdown in patients with an ED from various European and Asian countries; and (2) to assess differences related to diagnostic ED subtypes, age, and geography. METHODS The sample comprised 829 participants, diagnosed with an ED according to DSM-5 criteria from specialized ED units in Europe and Asia. Participants were assessed using the COVID-19 Isolation Scale (CIES). RESULTS Patients with binge eating disorder (BED) experienced the highest impact on weight and ED symptoms in comparison with other ED subtypes during lockdown, whereas individuals with other specified feeding and eating disorders (OFSED) had greater deterioration in general psychological functioning than subjects with other ED subtypes. Finally, Asian and younger individuals appeared to be more resilient. CONCLUSIONS The psychopathological changes in ED patients during the COVID-19 lockdown varied by cultural context and individual variation in age and ED diagnosis. Clinical services may need to target preventive measures and adapt therapeutic approaches for the most vulnerable patients.
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Extracellular vesicles in atherothrombosis and cardiovascular disease: Friends and foes.
Giró, O, Jiménez, A, Pané, A, Badimon, L, Ortega, E, Chiva-Blanch, G
Atherosclerosis. 2021;:61-75
Abstract
Extracellular vesicles (EV, exosomes and microvesicles -MV-) are 30-1000 nm particles surrounded by a phospholipid bilayer membrane that are released from almost all cell types through several pathways. EV encapsulate bioactive molecules, and the molecular cargo is determined by the trigger stimulating its release, reflecting its cell origin and biological functions. This review is primarily focused on the latest evidence of the roles of EV, released from cells involved in the different stages of atherothrombosis. The potential translation of this information to the clinical arena is also discussed. EV can have both pro- and anti-atherothrombotic effects depending on several factors, such as the type of vesicle (MV/exosome), its molecular cargo, its cell of origin, and the context in which are generated, i.e., the stimulus triggering its release. In fact, EV actively participate in every step of atherosclerosis onset and progression, and also in thrombus formation leading to a major adverse cardiovascular event. Moreover, EV have a determinant role in fibrous cap stability, thus determining the propensity of the plaque to rupture. On the other hand, and again, conditioned by the context and stimulus instigating its secretion, some EV may have protective biological functions, perhaps as a compensatory mechanism or even with reparative or regenerative potential. Therefore, the study of the implication of EV in atherothrombosis might be of relevance to unveil new therapeutic targets, vectors and biomarkers of cardiovascular disease (CVD).
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Cardiovascular and mortality benefits of sodium-glucose co-transporter-2 inhibitors in patients with type 2 diabetes mellitus: CVD-Real Catalonia.
Real, J, Vlacho, B, Ortega, E, Vallés, JA, Mata-Cases, M, Castelblanco, E, Wittbrodt, ET, Fenici, P, Kosiborod, M, Mauricio, D, et al
Cardiovascular diabetology. 2021;(1):139
Abstract
BACKGROUND Evidence from prospective cardiovascular (CV) outcome trials in type 2 diabetes (T2DM) patients supports the use of sodium-glucose co-transporter-2 inhibitors (SGLT2i) to reduce the risk of CV events. In this study, we compared the risk of several CV outcomes between new users of SGLT2i and other glucose-lowering drugs (oGLDs) in Catalonia, Spain. METHODS CVD-REAL Catalonia was a retrospective cohort study using real-world data routinely collected between 2013 and 2016. The cohorts of new users of SGLT2i and oGLDs were matched by propensity score on a 1:1 ratio. We compared the incidence rates and hazard ratio (HR) for all-cause death, hospitalization for heart failure, chronic kidney disease, and modified major adverse CV event (MACE; all-cause mortality, myocardial infarction, or stroke). RESULTS After propensity score matching, 12,917 new users were included in each group. About 27% of users had a previous history of CV disease. In the SGLT2i group, the exposure time was 60% for dapagliflozin, 26% for empagliflozin and 14% for canagliflozin. The use of SGLT2i was associated with a lower risk of heart failure (HR: 0.59; 95% confidence interval [CI] 0.47-0.74; p < 0.001), all-cause death (HR = 0.41; 95% CI 0.31-0.54; p < 0.001), all-cause death or heart failure (HR = 0.55; 95% CI 0.47-0.63; p < 0.001), modified MACE (HR = 0.62; 95% CI 0.52-0.74; p < 0.001), and chronic kidney disease (HR = 0.66; 95% CI 0.54-0.80; p < 0.001). CONCLUSIONS In this large, retrospective observational study of patients with T2DM from a Catalonia, initiation of SGLT-2i was associated with lower risk of mortality, as well as heart failure and CKD.
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Differential Health Effects on Inflammatory, Immunological and Stress Parameters in Professional Soccer Players and Sedentary Individuals after Consuming a Synbiotic. A Triple-Blinded, Randomized, Placebo-Controlled Pilot Study.
Quero, CD, Manonelles, P, Fernández, M, Abellán-Aynés, O, López-Plaza, D, Andreu-Caravaca, L, Hinchado, MD, Gálvez, I, Ortega, E
Nutrients. 2021;13(4)
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Plain language summary
Synbiotic, a mixture of prebiotics and probiotics, is known to improve neurotransmitter interactions, immune, inflammatory, and stress responses by modulating the gut microbial composition. It is also believed that physical activity plays an important role in the modulation of immune function and stress response. The purpose of this triple-blinded, randomized, placebo-controlled pilot study was to evaluate the health benefits of symbiotic intervention in fourteen sedentary students and thirteen soccer players, especially in terms of improving immunophysiological and metabolic parameters. The 300mg of symbiotic intervention contained Bifidobacterium lactis CBP-001010, Lactobacillus rhamnosus CNCM I-4036, Bifidobacterium longum ES1(109 colony-forming unit), and fructooligosaccharides (200 mg) plus 1.5 mg of zinc, 8.25 µg of selenium, 0.75 µg of vitamin, and maltodextrin. Following a one-month intervention with synbiotic formulation, soccer players showed improvements in anxiety, sleep quality and stress, a slight reduction in proinflammatory cytokine IL-1β, an exercise-induced significant increase in dopamine and a slight elevation of corticotropin-releasing hormone. For confirmation of results of this pilot study and to assess more significant effects of symbiotic intervention in athletes as well as in the general population, longer-term robust studies are required. The findings of this study can help healthcare professionals understand the extensive health benefits of synbiotic intervention and its relationship to physical activity.
Abstract
The main objective of this research was to carry out an experimental study, triple-blind, on the possible immunophysiological effects of a nutritional supplement (synbiotic, Gasteel Plus®, Heel España S.A.U.), containing a mixture of probiotic strains, such as Bifidobacterium lactis CBP-001010, Lactobacillus rhamnosus CNCM I-4036, and Bifidobacterium longum ES1, as well as the prebiotic fructooligosaccharides, on both professional athletes and sedentary people. The effects on some inflammatory/immune (IL-1β, IL-10, and immunoglobulin A) and stress (epinephrine, norepinephrine, dopamine, serotonin, corticotropin-releasing hormone (CRH), Adrenocorticotropic hormone (ACTH), and cortisol) biomarkers were evaluated, determined by flow cytometer and ELISA. The effects on metabolic profile and physical activity, as well as on various parameters that could affect physical and mental health, were also evaluated via the use of accelerometry and validated questionnaires. The participants were professional soccer players in the Second Division B of the Spanish League and sedentary students of the same sex and age range. Both study groups were randomly divided into two groups: a control group-administered with placebo, and an experimental group-administered with the synbiotic. Each participant was evaluated at baseline, as well as after the intervention, which lasted one month. Only in the athlete group did the synbiotic intervention clearly improve objective physical activity and sleep quality, as well as perceived general health, stress, and anxiety levels. Furthermore, the synbiotic induced an immunophysiological bioregulatory effect, depending on the basal situation of each experimental group, particularly in the systemic levels of IL-1β (increased significantly only in the sedentary group), CRH (decreased significantly only in the sedentary group), and dopamine (increased significantly only in the athlete group). There were no significant differences between groups in the levels of immunoglobulin A or in the metabolic profile as a result of the intervention. It is concluded that synbiotic nutritional supplements can improve anxiety, stress, and sleep quality, particularly in sportspeople, which appears to be linked to an improved immuno-neuroendocrine response in which IL-1β, CRH, and dopamine are clearly involved.