Physical activity shifts gut microbiota structure in aged subjects with overweight/obesity and metabolic syndrome.

We aimed to identify how physical activity (PA), within the context of a Mediterranean diet, affects metabolic variables and gut microbiota in older individuals with overweight/obesity and metabolic syndrome. Observational analysis was conducted as part of the PREDIMED-Plus study with 152 males and 145 females with overweight/obesity and metabolic syndrome. General assessments, anthropometric and biochemical measurements, and gut microbial 16S rRNA sequencing data were analyzed at baseline and 1-year of follow-up. Participants were stratified by tertiles of 1-year change in total PA-related energy expenditure ranging from -98.77 to 1099.99 METs (min/week). The total PA percentage of change was reduced in tertile 1 (-44.83 ± 24.94), increased in tertile 2 (28.96 ± 23.33) and tertile 3 (273.64 ± 221.42). Beta diversity analysis showed differences in the gut microbiota population within each tertile group. Significant differences were found at phylum, family, and genus levels in the gut microbiota of the three tertile groups at baseline and 1-year timepoint. Tertile 3, the group with the greatest increase in PA, was characterized by increases in their levels of Sutterella, Bilophila, and Lachnospira bacteria as well as a reduction in Collinsella. Moreover, this tertile showed a different pattern in its predicted metabolic capacities to the other groups. Our results have demonstrated that changes in PA such as lifestyle and Mediterranean diet induces specific variations in the gut microbiota profile. This modulation of gut microbiome populations and their metabolic capacities may contribute to the health of the aged individuals with overweight/obesity and metabolic syndrome.

Effect of Semaglutide on Regression and Progression of Glycemia in People With Overweight or Obesity but Without Diabetes in the SELECT Trial.

OBJECTIVE: To determine whether semaglutide slows progression of glycemia in people with cardiovascular disease and overweight or obesity but without diabetes. RESEARCH DESIGN AND METHODS: In a multicenter, double-blind trial, participants aged ≥45 years, with BMI ≥27 kg/m2, and with preexisting cardiovascular disease but without diabetes (HbA1c <6.5%) were randomized to receive subcutaneous semaglutide (2.4 mg weekly) or placebo. Major glycemic outcomes were HbA1c and proportions achieving biochemical normoglycemia (HbA1c <5.7%) and progressing to biochemical diabetes (HbA1c ≥6.5%). RESULTS: Of 17,604 participants, 8,803 were assigned to semaglutide and 8,801 to placebo. Mean ± SD intervention exposure was 152 ± 56 weeks and follow-up 176 ± 40 weeks. In both treatment arms mean nadir HbA1c for participants was at 20 weeks. Thereafter, HbA1c increased similarly in both arms, with a mean difference of -0.32 percentage points (95% CI -0.33 to -0.30; -3.49 mmol/mol [-3.66 to -3.32]) and with the difference favoring semaglutide throughout the study (P < 0.0001). Body weight plateaued at 65 weeks and was 8.9% lower with semaglutide. At week 156, a greater proportion treated with semaglutide were normoglycemic (69.5% vs. 35.8%; P < 0.0001) and a smaller proportion had biochemical diabetes by week 156 (1.5% vs. 6.9%; P < 0.0001). The number needed to treat was 18.5 to prevent a case of diabetes. Both regression and progression were dependent on glycemia at baseline, with the magnitude of weight reduction important in mediating 24.5% of progression and 27.1% of regression. CONCLUSIONS: In people with preexisting cardiovascular disease and overweight or obesity but without diabetes, long-term semaglutide increases regression to biochemical normoglycemia and reduces progression to biochemical diabetes but does not slow glycemic progression over time.

Gut microbiota dynamics and association with chronic kidney disease: A longitudinal study within the PREDIMED-Plus trial.

AIMS: Chronic kidney disease (CKD) represents a global health concern, disproportionately affecting the elderly with heightened cardiovascular risk. The emerging focus on the gut microbiota's role in CKD pathophysiology represents a pivotal area in nephrology; however, the evidence on this topic is limited. This observational prospective study, in the framework of the PREDIMED-Plus trial, investigates associations between gut microbiota composition and the 1-year trajectory of CKD in 343 participants aged 55-75 years with high cardiovascular risk. MATERIALS AND METHODS: Kidney function was assessed at baseline and at 1-year of follow-up through the estimated glomerular filtration rate based on cystatin C (eGFR-CysC) and CKD defined by eGFR-CysC <60 mL/min/1.73 m2. Participants were grouped based on their 1-year CKD trajectory: Group 1 maintained normal status or improved from CKD to normal, while Group 2 maintained CKD or worsened from normal to CKD. Fecal microbiota composition was assessed through 16S sequencing. KEY FINDINGS: We observed differences in gut microbiota composition between CKD trajectory groups. Notably, the baseline relative abundance of Lachnoclostridium and Lachnospira, both butyrate-producing genera, was lower in participants maintaining or progressing to CKD. Longitudinally, a decrease in Lachnospira abundance was associated with CKD progression. The improved Chao1 index after 1-year follow-up suggests a link between enhanced microbial richness and stable/better kidney function. SIGNIFICANCE: The findings underscore the potential of gut microbiota analysis in non-invasively monitoring CKD, especially in older populations, and hint at future interventions targeting gut microbiota to manage CKD progression. Further research is needed for causal relationships and generalizability.

A Systematic Review of Proteomics in Obesity: Unpacking the Molecular Puzzle.

PURPOSE OF REVIEW: The present study aims to review the existing literature to identify pathophysiological proteins in obesity by conducting a systematic review of proteomics studies. Proteomics may reveal the mechanisms of obesity development and clarify the links between obesity and related diseases, improving our comprehension of obesity and its clinical implications. RECENT FINDINGS: Most of the molecular events implicated in obesity development remain incomplete. Proteomics stands as a powerful tool for elucidating the intricate interactions among proteins in the context of obesity. This methodology has the potential to identify proteins involved in pathological processes and to evaluate changes in protein abundance during obesity development, contributing to the identification of early disease predisposition, monitoring the effectiveness of interventions and improving disease management overall. Despite many non-targeted proteomic studies exploring obesity, a comprehensive and up-to-date systematic review of the molecular events implicated in obesity development is lacking. The lack of such a review presents a significant challenge for researchers trying to interpret the existing literature. This systematic review was conducted following the PRISMA guidelines and included sixteen human proteomic studies, each of which delineated proteins exhibiting significant alterations in obesity. A total of 41 proteins were reported to be altered in obesity by at least two or more studies. These proteins were involved in metabolic pathways, oxidative stress responses, inflammatory processes, protein folding, coagulation, as well as structure/cytoskeleton. Many of the identified proteomic biomarkers of obesity have also been reported to be dysregulated in obesity-related disease. Among them, seven proteins, which belong to metabolic pathways (aldehyde dehydrogenase and apolipoprotein A1), the chaperone family (albumin, heat shock protein beta 1, protein disulfide-isomerase A3) and oxidative stress and inflammation proteins (catalase and complement C3), could potentially serve as biomarkers for the progression of obesity and the development of comorbidities, contributing to personalized medicine in the field of obesity. Our systematic review in proteomics represents a substantial step forward in unravelling the complexities of protein alterations associated with obesity. It provides valuable insights into the pathophysiological mechanisms underlying obesity, thereby opening avenues for the discovery of potential biomarkers and the development of personalized medicine in obesity.

Evolutionary analysis of indeterminate cytology and risk of malignancy in a thyroid nodule unit.

OBJECTIVE: The objective of this study was to analyze the evolution in the diagnosis and management of indeterminate thyroid nodules over three time periods. METHODS: 3020 patients with thyroid nodules underwent cytological evaluation during three periods (2006-2008, 2012-2014, 2017-2019). Distribution of diagnostic cytologies, risk of malignancy, diagnostic performance indices of FNA, and cytologic-histologic correlation in indeterminate cytologies were analyzed. RESULTS: only 2.2% of cytology tests were insufficient for a diagnosis. 86.9% cytologies were benign, 1.7% malignant, and 11.4% indeterminate. Indeterminate cytology rates were 15.9% (2006-2008), 10.1% (2012-2014), and 10% (2017-2019). Surgery was performed in 13% of benign cytology, result-ing in malignant histology in 2.7%. All malignant and suspicious cytologies underwent surgery: malig-nancy confirmed in 98% and 77% of cases, respectively. All 'indeterminate with atypia' cytologies (2006-2008) and Bethesda IV (2012-2014; 2017-2019) un-derwent surgery, with malignancy confirmed in 19.6%, 43.8%, and 25.7%, respectively. In the 'inde-terminate without atypia' category (2006-2008) and Bethesda III (2012-2014; 2017-2019), diagnostic surgery was performed in 57.7%, 78.6%, and 59.4%, respectively, with malignancy confirmed in 3.3%, 20.5%, and 31.6%. The FNA sensitivity was 91.6% with a negative predictive value greater than 96% in all periods. The specificity exceeded 75% in the last two periods. CONCLUSION: Bethesda system reduces indeterminate cytologies and improves the accuracy of FNA diagnosis. We reported a higher proportion of malignancy than expected in Bethesda III, underscoring the importance of having institution-specific data to guide decision-making. However, there is a need for risk stratification tools that allow for conservative management in low-risk cases.

Effect of a nutritional intervention based on an energy-reduced Mediterranean diet on environmental impact.

OBJECTIVE: To estimate the environmental impact of a dietary intervention based on an energy-reduced Mediterranean diet (MedDiet) after one year of follow-up. METHODS: Baseline and 1-year follow-up data were used for 5800 participants aged 55-75 years with metabolic syndrome in the PREDIMED-Plus study. Food intake was estimated through a validated semiquantitative food consumption frequency questionnaire, and adherence to the MedDiet was estimated through the Diet Score. Using the EAT-Lancet Commission tables we assessed the influence of dietary intake on environmental impact (through five indicators: greenhouse gas emissions (GHG), land use, energy used, acidification and potential eutrophication). Using multivariable linear regression models, the association between the intervention and changes in each of the environmental factors was assessed. Mediation analyses were carried out to estimate to what extent changes in each of 2 components of the intervention, namely adherence to the MedDiet and caloric reduction, were responsible for the observed reductions in environmental impact. RESULTS: We observed a significant reduction in the intervention group compared to the control group in acidification levels (-13.3 vs. -9.9 g SO2-eq), eutrophication (-5.4 vs. -4.0 g PO4-eq) and land use (-2.7 vs. -1.8 m2). Adherence to the MedDiet partially mediated the association between intervention and reduction of acidification by 15 %, eutrophication by 10 % and land use by 10 %. Caloric reduction partially mediated the association with the same factors by 55 %, 51 % and 38 % respectively. In addition, adherence to the MedDiet fully mediated the association between intervention and reduction in GHG emissions by 56 % and energy use by 53 %. CONCLUSIONS: A nutritional intervention based on consumption of an energy-reduced MedDiet for one year was associated with an improvement in different environmental quality parameters.

Type 1 diabetes-related distress: Current implications in care.

Type 1 diabetes (T1D) is a complex chronic disease associated with major health and economic consequences, also involving important issues in the psychosocial sphere. In this regard, T1D-related distress, defined as the emotional burden of living with T1D, has emerged as a specific entity related to the disease. Diabetes distress (DD) is an overlooked but prevalent condition in people living with T1D, and has significant implications in both glycemic control and mental health in this population. Although overlapping symptoms may be found between DD and mental health disorders, specific approaches should be performed for the diagnosis of this problem. In recent years, different DD-targeted interventions have been postulated, including behavioral and psychosocial strategies. Moreover, new technologies in this field may be helpful to address DD in people living with T1D. In this article, we summarize the current knowledge on T1D-related distress, and we also discuss the current approaches and future perspectives in its management.

Dietary intake of Perfluorooctanesulfonic acid (PFOS) and glucose homeostasis parameters in a non-diabetic senior population.

BACKGROUND: Endocrine disruptors (EDs) have emerged as potential contributors to the development of type-2 diabetes. Perfluorooctane sulfonate (PFOS), is one of these EDs linked with chronic diseases and gathered attention due to its widespread in food. OBJECTIVE: To assess at baseline and after 1-year of follow-up associations between estimated dietary intake (DI) of PFOS, and glucose homeostasis parameters and body-mass-index (BMI) in a senior population of 4600 non-diabetic participants from the PREDIMED-plus study. METHODS: Multivariable linear regression models were conducted to assess associations between baseline PFOS-DI at lower bound (LB) and upper bound (UB) established by the EFSA, glucose homeostasis parameters and BMI. RESULTS: Compared to those in the lowest tertile, participants in the highest tertile of baseline PFOS-DI in LB and UB showed higher levels of HbA1c [ß-coefficient(CI)] [0.01 %(0.002 to 0.026), and [0.06 mg/dL(0.026 to 0.087), both p-trend ≤ 0.001], and fasting plasma glucose in the LB PFOS-DI [1.05 mg/dL(0.050 to 2.046),p-trend = 0.022]. Prospectively, a positive association between LB of PFOS-DI and BMI [0.06 kg/m2(0.014 to 0.106) per 1-SD increment of energy-adjusted PFOS-DI was shown. Participants in the top tertile showed an increase in HOMA-IR [0.06(0.016 to 0.097), p-trend = 0.005] compared to participants in the reference tertile after 1-year of follow-up. DISCUSSION: This is the first study to explore the association between DI of PFOS and glucose homeostasis. In this study, a high baseline DI of PFOS was associated with a higher levels of fasting plasma glucose and HbA1c and with an increase in HOMA-IR and BMI after 1-year of follow-up.

Effect of 1-year lifestyle intervention with energy-reduced Mediterranean diet and physical activity promotion on the gut metabolome and microbiota: a randomized clinical trial.

BACKGROUND: The health benefits of the Mediterranean diet (MedDiet) have been linked to the presence of beneficial gut microbes and related metabolites. However, its impact on the fecal metabolome remains poorly understood. OBJECTIVES: Our goal was to investigate the weight-loss effects of a 1-y lifestyle intervention based on an energy-reduced MedDiet coupled with physical activity (intervention group), compared with an ad libitum MedDiet (control group), on fecal metabolites, fecal microbiota, and their potential association with cardiovascular disease risk factors. METHODS: A total of 400 participants (200 from each study group), aged 55-75 y, and at high cardiovascular disease risk, were included. Dietary and lifestyle information, anthropometric measurements, blood biochemical parameters, and stool samples were collected at baseline and after 1 y of follow-up. Liquid chromatography-tandem mass spectrometry was used to profile endogenous fecal metabolites, and 16S amplicon sequencing was employed to profile the fecal microbiota. RESULTS: Compared with the control group, the intervention group exhibited greater weight loss and improvement in various cardiovascular disease risk factors. We identified intervention effects on 4 stool metabolites and subnetworks primarily composed of bile acids, ceramides, and sphingosines, fatty acids, carnitines, nucleotides, and metabolites of purine and the Krebs cycle. Some of these were associated with changes in several cardiovascular disease risk factors. In addition, we observed a reduction in the abundance of the genera Eubacterium hallii group and Dorea, and an increase in alpha diversity in the intervention group after 1 y of follow-up. Changes in the intervention-related microbiota profiles were also associated with alterations in different fecal metabolite subnetworks and some cardiovascular disease risk factors. CONCLUSIONS: An intervention based on an energy-reduced MedDiet and physical activity promotion, compared with an ad libitum MedDiet, was associated with improvements in cardiometabolic risk factors, potentially through modulation of the fecal microbiota and metabolome. This trial was registered at https://www.isrctn.com/ as ISRCTN89898870 (https://doi.org/10.1186/ISRCTN89898870).

Bone metabolism and inflammatory biomarkers in radiographic and non-radiographic axial spondyloarthritis patients: a comprehensive evaluation.

Introduction: Axial spondyloarthritis (axSpA) is a heterogeneous disease that can be represented by radiographic axSpA (r-axSpA) and non-radiographic axSpA (nr-axSpA). This study aimed to evaluate the relationship between the markers of inflammation and bone turnover in r-axSpA patients and nr-axSpA patients. Methods: A cross-sectional study included 29 r-axSpA patients, 10 nr-axSpA patients, and 20 controls matched for age and sex. Plasma markers related to bone remodeling such as human procollagen type 1 N-terminal propeptide (P1NP), sclerostin, tartrate-resistant acid phosphatase 5b (TRACP5b), receptor activator of nuclear factor kappa B ligand (RANKL), and osteoprotegerin (OPG) were measured by an ELISA kit. A panel of 92 inflammatory molecules was analyzed by proximity extension assay. Results: R-axSpA patients had decreased plasma levels of P1NP, a marker of bone formation, compared to controls. In addition, r-axSpA patients exhibited decreased plasma levels of sclerostin, an anti-anabolic bone hormone, which would not explain the co-existence of decreased plasma P1NP concentration; however, sclerostin levels could also be influenced by inflammatory processes. Plasma markers of osteoclast activity were similar in all groups. Regarding inflammation-related molecules, nr-axSpA patients showed increased levels of serum interleukin 13 (IL13) as compared with both r-axSpA patients and controls, which may participate in the prevention of inflammation. On the other hand, r-axSpA patients had higher levels of pro-inflammatory molecules compared to controls (i.e., IL6, Oncostatin M, and TNF receptor superfamily member 9). Correlation analysis showed that sclerostin was inversely associated with IL6 and Oncostatin M among others. Conclusion: Altogether, different inflammatory profiles may play a role in the development of the skeletal features in axSpA patients particularly related to decreased bone formation. The relationship between sclerostin and inflammation and the protective actions of IL13 could be of relevance in the axSpA pathology, which is a topic for further investigation.

Non-alcoholic fatty liver disease in patients with morbid obesity: the gut microbiota axis as a potential pathophysiology mechanism.

BACKGROUND/AIM: Alterations in gut microbiota are associated with the pathogenesis of metabolic diseases, including metabolic-associated fatty liver disease (MAFLD). The aim of this study was to evaluate gut microbiota composition and functionality in patients with morbid obesity with different degrees of MAFLD, as assessed by biopsy. SUBJECTS/METHODS: 110 patients with morbid obesity were evaluated by biopsy obtained during bariatric surgery for MAFLD. Stool samples were collected prior to surgery for microbiota analysis. RESULTS: Gut microbiota from patients with steatosis and non-alcoholic steatohepatitis (NASH) were characterized by an enrichment in Enterobacteriaceae (an ethanol-producing bacteria), Acidaminococcus and Megasphaera and the depletion of Eggerthellaceae and Ruminococcaceae (SCFA-producing bacteria). MAFLD was also associated with enrichment of pathways related to proteinogenic amino acid degradation, succinate production, menaquinol-7 (K2-vitamin) biosynthesis, and saccharolytic and proteolytic fermentation. Basic histological hepatic alterations (steatosis, necroinflammatory activity, or fibrosis) were associated with specific changes in microbiota patterns. Overall, the core microbiome related to basic histological alterations in MAFLD showed an increase in Enterobacteriaceae and a decrease in Ruminococcaceae. Specifically, Escherichia coli was associated with steatosis and necroinflammatory activity, whilst Escherichia-shigella was associated with fibrosis and necroinflammatory activity. CONCLUSIONS: We established a link between gut microbiota alterations and histological injury in liver diagnosis using biopsy. Harmful products such as ethanol or succinate may be involved in the pathogenesis and progression of MAFLD. Thus, these alterations in gut microbiota patterns and their possible metabolic pathways could add information to the classical predictors of MAFLD severity and suggest novel metabolic targets.

Coronavirus disease 2019 is associated with long-term depressive symptoms in Spanish older adults with overweight/obesity and metabolic syndrome.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has serious physiological and psychological consequences. The long-term (>12 weeks post-infection) impact of COVID-19 on mental health, specifically in older adults, is unclear. We longitudinally assessed the association of COVID-19 with depression symptomatology in community-dwelling older adults with metabolic syndrome within the framework of the PREDIMED-Plus cohort. METHODS: Participants (n = 5486) aged 55-75 years were included in this longitudinal cohort. COVID-19 status (positive/negative) determined by tests (e.g. polymerase chain reaction severe acute respiratory syndrome coronavirus 2, IgG) was confirmed via event adjudication (410 cases). Pre- and post-COVID-19 depressive symptomatology was ascertained from annual assessments conducted using a validated 21-item Spanish Beck Depression Inventory-II (BDI-II). Multivariable linear and logistic regression models assessed the association between COVID-19 and depression symptomatology. RESULTS: COVID-19 in older adults was associated with higher post-COVID-19 BDI-II scores measured at a median (interquartile range) of 29 (15-40) weeks post-infection [fully adjusted ß = 0.65 points, 95% confidence interval (CI) 0.15-1.15; p = 0.011]. This association was particularly prominent in women (ß = 1.38 points, 95% CI 0.44-2.33, p = 0.004). COVID-19 was associated with 62% increased odds of elevated depression risk (BDI-II ≥ 14) post-COVID-19 when adjusted for confounders (odds ratio; 95% CI 1.13-2.30, p = 0.008). CONCLUSIONS: COVID-19 was associated with long-term depression risk in older adults with overweight/obesity and metabolic syndrome, particularly in women. Thus, long-term evaluations of the impact of COVID-19 on mental health and preventive public health initiatives are warranted in older adults.

Microbial Phenolic Metabolites Are Associated with Improved Cognitive Health.

SCOPE: Diets rich in polyphenols has been associated with better cognitive performance. The aim of this study is to assess the relationship between microbial phenolic metabolites (MPM) in urine and cognition in the context of an older population at high cardiovascular risk. METHODS AND RESULTS: A cross-sectional analysis is conducted in 400 individuals of the PREDIMED-Plus study. Liquid chromatography coupled to mass spectrometry is used to identify urinary MPM. Mediterranean diet (MedDiet) adherence is estimated with a 17-item questionnaire and cognitive function is evaluated with a battery of neuropsychological tests. Multivariable-adjusted linear regression models are fitted to assess the relationship of urinary MPM with the MedDiet and cognitive tests. Protocatechuic acid and enterolactone glucuronide are associated with higher adherence to the MedDiet. Regarding cognitive function, protocatechuic acid, vanillic acid glucuronide, 3-hydroxybenzoic acid, enterodiol glucuronide, and enterolactone glucuronide are directly associated with a global composite score of all the cognitive tests. Furthermore, protocatechuic acid and enterolactone glucuronide are associated with higher scores in the Mini-Mental State Examination, whereas enterodiol glucuronide is associated with improved Clock Drawing Test scores. CONCLUSIONS: These results suggest that the MedDiet is linked to MPM associated with better cognitive performance in an older population.

Changes in Oxidative Stress and Intestinal Permeability during Pregnancy in Women with Gestational Diabetes Mellitus Treated with Metformin or Insulin and Healthy Controls: A Randomized Controlled Trial.

Both oxidative stress and intestinal permeability are increased in hyperglycemic situations and have been shown to be reduced by metformin in type 2 diabetes mellitus (T2DM) patients. The aim of this study was to elucidate the effect of metformin on oxidative stress and intestinal permeability in women with gestational diabetes mellitus (GDM) treated with metformin compared to those treated with insulin and healthy controls. A total of 120 women were included from August 2016 to February 2022: 41 received metformin (MET group), 38 received insulin (INS group), and 41 were healthy controls. Baseline and antenatal visits were carried out at 25.4 ± 4.8 and 36.1 ± 0.8 weeks of pregnancy, respectively. Advanced oxidation protein products (AOPPs), total antioxidant capacity (TAC), and zonulin levels were measured at every visit. Zonulin levels from baseline to prepartum visit increased significantly in both healthy controls (0.6 ± 0.9 to 1.2 ± 1.7 ng/mL, p = 0.004) and the INS group (0.4 ± 0.3 to 0.6 ± 0.5 ng/mL, p = 0.034) but did not significantly change in the MET group (0.4 ± 0.4 to 0.5 ± 0.4 ng/mL, p = 0.202). However, TAC and AOPP levels significantly increased in women with GDM, both in the INS and MET groups but not in the healthy controls. In conclusion, in our population, metformin has been shown to avoid an increase in intestinal permeability but failed to avoid an increase in oxidative stress related to hyperglycemia.

The Relationship between Depressive Symptoms, Quality of Life and miRNAs 8 Years after Bariatric Surgery.

(1) Background: There are conflicting results on whether weight loss after bariatric surgery (BS) might be associated with quality of life (QoL)/depressive symptomatology. We aim to determine whether BS outcomes are associated with QoL/depressive symptomatology in studied patients at the 8-year follow-up after BS, as well as their relationship with different serum proteins and miRNAs. (2) Methods: A total of 53 patients with class III obesity who underwent BS, and then classified into "good responders" and "non-responders" depending on the percentage of excess weight lost (%EWL) 8 years after BS (%EWL ≥ 50% and %EWL < 50%, respectively), were included. Basal serum miRNAs and different proteins were analysed, and patients completed tests to evaluate QoL/depressive symptomatology at 8 years after BS. (3) Results: The good responders group showed higher scores on SF-36 scales of physical functioning, role functioning-physical, role functioning-emotional, body pain and global general health compared with the non-responders. The expression of hsa-miR-101-3p, hsa-miR-15a-5p, hsa-miR-29c-3p, hsa-miR-144-3p and hsa-miR-19b-3p were lower in non-responders. Hsa-miR-19b-3p was the variable associated with the response to BS in a logistic regression model. (4) Conclusions: The mental health of patients after BS is limited by the success of the intervention. In addition, the expression of basal serum miRNAs related to depression/anxiety could predict the success of BS.

Associations between ultra-processed food consumption and kidney function in an older adult population with metabolic syndrome.

BACKGROUND & AIMS: Ultra-processed food (UPF) consumption has increased dramatically over the last decades worldwide. Although it has been linked to some cardiometabolic comorbidities, there is limited evidence regarding kidney function. This study aimed to cross-sectionally and longitudinally assess the association between UPF consumption and estimated-glomerular filtration rate (eGFR) based on Cystatin C (CysC). METHODS: Older adults (mean age 65 ± 5.0 years, 46% women) with overweight/obesity and metabolic syndrome (MetS) who had available data of CysC at baseline (n = 1909), at one-year and at 3-years of follow-up (n = 1700) were analyzed. Food consumption was assessed using a validated 143-item semi-quantitative food frequency questionnaire and UPF consumption (% of g/d) at baseline and changes after one-year of follow-up were estimated according to NOVA classification system. Multivariable-adjusted linear and logistic regression models were performed to evaluate the cross-sectional associations between UPF consumption with eGFR levels and decreased kidney function (eGFR <60 ml/min/1.73 m2) at baseline. Multivariable-adjusted mixed-effects linear regression models were fitted to investigate the associations between one-year changes in UPF and eGFR over 3-years of follow-up. RESULTS: Individuals with the highest baseline UPF consumption showed lower eGFR (ß: -3.39 ml/min/1.73 m2; 95% CI: -5.59 to -1.20) and higher odds of decreased kidney function (OR: 1.64; 95% CI: 1.21 to 2.22) at baseline, compared to individuals in the lowest tertile. Participants in the highest tertile of one-year changes in UPF consumption presented a significant decrease in eGFR after one-year of follow-up (ß: -1.45 ml/min/1.73 m2; 95% CI: -2.90 to -0.01) as well as after 3-years of follow-up (ß: -2.18 ml/min/1.73 m2; 95% CI: -3.71 to -0.65) compared to those in the reference category. CONCLUSIONS: In a Mediterranean population of older adults with overweight/obesity and MetS, higher UPF consumption at baseline and one-year changes towards higher consumption of UPF were associated with worse kidney function at baseline and over 3-years of follow-up, respectively. CLINICAL TRIAL REGISTRY NUMBER: ISRCTN89898870.

Association of adiposity and its changes over time with COVID-19 risk in older adults with overweight/obesity and metabolic syndrome: a longitudinal evaluation in the PREDIMED-Plus cohort.

BACKGROUND: Cross-sectionally, older age and obesity are associated with increased coronavirus disease-2019 (COVID-19) risk. We assessed the longitudinal associations of baseline and changes in adiposity parameters with COVID-19 incidence in older adults at high cardiovascular risk. METHODS: This analysis included 6874 men and women (aged 55-75 years) with overweight/obesity and metabolic syndrome in the PREDIMED-Plus lifestyle intervention trial for cardiovascular risk reduction. Body weight, body-mass-index (BMI), waist circumference, waist-to-height ratio (WHtR), and a body shape index (ABSI) were measured at baseline and annual follow-up visits. COVID-19 was ascertained by an independent Event Committee until 31 December 2021. Cox regression models were fitted to evaluate the risk of COVID-19 incidence based on baseline adiposity parameters measured 5-6 years before the pandemic and their changes at the visit prior to censoring. RESULTS: At the time of censoring, 653 incident COVID-19 cases occurred. Higher baseline body weight, BMI, waist circumference, and WHtR were associated with increased COVID-19 risk. During the follow-up, every unit increase in body weight (HRadj (95%CI): 1.01 (1.00, 1.03)) and BMI (HRadj: 1.04 (1.003, 1.08)) was associated with increased COVID-19 risk. CONCLUSIONS: In older adults with overweight/obesity, clinically significant weight loss may protect against COVID-19. TRIAL REGISTRATION: This study is registered at the International Standard Randomized Controlled Trial (ISRCT; http://www.isrctn.com/ISRCTN89898870 ).

Epigenetic Marks as Predictors of Metabolic Response to Bariatric Surgery: Validation from an Epigenome Wide Association Study.

Little is known about the potential role of epigenetic marks as predictors of the resolution of obesity-related comorbidities after bariatric surgery. In this study, 20 patients were classified according to the metabolic improvement observed 6 months after sleeve gastrectomy, based on the diagnosis of metabolic syndrome, into responders if metabolic syndrome reversed after bariatric surgery (n = 10) and non-responders if they had metabolic syndrome bariatric surgery (n = 10). Blood DNA methylation was analyzed at both study points using the Infinium Methylation EPIC Bead Chip array-based platform. Twenty-six CpG sites and their annotated genes, which were previously described to be associated with metabolic status, were evaluated. Cg11445109 and cg19469447 (annotated to Cytochrome P450 2E1 (CYP2E1) gene) were significantly more hypomethylated in the responder group than in the non-responder group at both study points, whilst cg25828445 (annotated to Nucleolar Protein Interacting With The FHA Domain Of MKI67 Pseudogene 3 (NIFKP3) gene) showed to be significantly more hypermethylated in the non-responder group compared to the responder group at both study points. The analysis of the methylation sites annotated to the associated genes showed that CYP2E1 had 40% of the differentially methylated CpG sites, followed by Major Histocompatibility Complex, Class II, DR Beta 1 (HLA-DRB1) (33.33%) and Zinc Finger Protein, FOG Family Member 2 (ZFPM2) (26.83%). Cg11445109, cg19469447 and cg25828445 could have a role in the prediction of metabolic status and potential value as biomarkers of response to bariatric surgery.