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Background: Bariatric surgery (BS) is the most effective intervention for severe obesity, leading to sustained weight loss, reduced obesity-related comorbidities, and cardiovascular mortality., Aim: To assess changes in high-density lipoprotein (HDL) functions [cholesterol efflux capacity (CEC) and anti-inflammatory capacity] at different follow-up times in patients with severe obesity undergoing BS., Methods: A prospective observational study within a cohort of consecutively enrolled patients with severe obesity scheduled to undergo BS. In total, 62 participants (77% women), with a mean age of 42.1 years (SD 9.33 years) underwent BS. Regarding the surgical procedure, 27 (43.5%) underwent sleeve gastrectomy and 35 (56.5%) Roux-en-Y gastric bypass. All patients were evaluated preoperatively and at 1, 3, 6, and 12 months after surgery., Results: A decrease in body mass index and an improvement in the systemic lipid profile, indicated by reductions in total cholesterol, low-density lipoprotein cholesterol (LDLc), and remnant cholesterol, and an increase in HDL cholesterol (HDLc) was observed (all p trend < 0.001). Time-series comparisons vs. baseline showed that, in general, anthropometric measures, glycemia, total cholesterol, LDLc, and remnant cholesterol decreased at all follow-ups, whereas HDLc and triglyceride concentrations significantly improved vs. baseline from 6 months, reaching at 12 months the highest HDLc levels (29.6%, p  < 0.001) and the lowest circulating triglycerides (-30%, p  < 0.001). Although HDL's anti-inflammatory ability worsens after surgery, the HDL-mediated CEC linearly increased after surgery (for both p trend < 0.013)., Conclusion: BS improves the lipid profile both quantitatively and qualitatively after 1 year, specifically enhancing HDL-mediated cholesterol efflux capacity, which may contribute to a reduced cardiovascular risk in individuals with severe obesity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Castañer, Pérez-Vega, Álvarez, Vázquez, Casajoana, Blanchart, Gaixas, Schröder, Zomeño, Subirana, Muñoz-Aguayo, Fitó, Benaiges, Goday and Oliveras.)

Introduction: Distinct androgen formulations have been used as gender-affirming hormone treatment, but little is known about the specific changes that may occur in the ovary depending on the testosterone preparation used. The study aims to evaluate the histological modifications of the ovarian tissue and the hormonal changes after gender-affirming surgery based on the testosterone preparation employed, such as testosterone cypionate or undecanoate., Design: Unicenter transversal cohort study., Materials and Methods: Sixty transmasculine persons before and after gender-affirming surgery. A histological examination of the ovaries was conducted, including the follicular population and the characterization of the ovarian stroma. Hormonal status (testosterone, estradiol, FSH, and LH) were also assessed before and after the procedure., Results: The median age of participants was similar between the two groups (27.9 vs. 26.7 years, p = 0.27). There were no differences in all hormonal determinations before gender-affirming surgery between the groups. After surgery, FSH levels increased significantly, especially in the testosterone undecanoate group compared to the cypionate group (72.3 vs. 38.3 U/L, p = 0.02), consistent with LH determinations (43.0 vs. 23.4 U/L, p = 0.02). However, no regimen modification was required for any individual. No statistical differences were observed in any parameter concerning the follicular population, nor were there any variances in the thickness of the tunica albuginea (p = 0.85) or the proportion of luteinized stromal cells. Nevertheless, there was a tendency toward increased luteinization in the testosterone cypionate group (88.2% vs. 76.9%, p > 0.05)., Conclusions: In a cohort of transmasculine individuals using different androgen preparations, histological analysis of ovarian tissue revealed comparable findings. Both groups exhibited similar follicular populations and comparable modifications in stromal tissue. However, significant differences were observed in hormonal profiles, although no modification in testosterone dosage was needed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Borrás, Barral, Fabregues, Casals, Mora, Orois, Méndez, Saco, Goday and Manau.)

This project aims to establish the acceptability and satiety of a hybrid snack containing plant protein and a small percentage of animal protein compared to a meat-based snack., Design: Randomised, crossover, double-blind, controlled post-prandial trial involving 24 participants (18-30 years), with two interventions: (a) a hybrid snack containing plant protein derived from chickpeas and 6.6% lean high-quality pork meat; and (b) a meat-based snack containing 90% lean pork meat., Methods: General, life-style, sensory acceptability questionnaire, and the following laboratory analyses were performed: lipid profile, endocannabinoids, and related compounds., Results: Sensory questionnaires showed in general good acceptability for both bars. Additionally, there was a greater increase in glycemia at 30, 60, and 90 min after consuming the hybrid snack compared to the meat-based snack, with no changes in the lipid profile. Regarding the endocannabinoid compounds and related compounds, the compound N-palmitoleoyl ethanolamine in the acylethanolamide group showed higher levels overall following the consumption of the hybrid snack compared to the meat-based snack, particularly at 2 h., Conclusions: The hybrid snack was associated with changes in endocannabinoid-like compounds. Therefore, it may provide a lasting satiating effect, while complementing the protein profile of plant-based foods with the quality of animal protein.

Objectives: The evidence on water intake in the prevention of kidney function decline is scarce at population level in well-being individuals at high cardiovascular risk. Therefore, we aimed to longitudinally evaluate the associations between total water intake and subtypes and kidney function, through estimated-Glomerular Filtration Rate (eGFR)., Methods: Three-year prospective analysis conducted in 1986 older adults (aged 55-75 year) with overweight/obesity and metabolic syndrome from the PREDIMED-Plus study. Water intake was assessed using validated beverage and food frequency questionnaires. Serum creatinine-based eGFR (SCr-based eGFR; ml/min/1.73 m 2 ) was estimated using the CKD-EPI equation at baseline, one-year and 3-years of follow-up. Mixed-effects linear regression models were fitted to evaluate the associations between baseline total water intake and subtypes, and SCr-based eGFR over 3-years of follow-up., Results: Participants in the highest baseline tertile of total water intake, plain water and water from all fluids showed a lower decrease in SCr-based eGFR after 3-years of follow-up, compared to those in the lowest tertile. Participants with the highest tap water consumption showed a lower SCr-based eGFR decline after 1-year and 3-years of follow-up, in comparerd to participants in the lowest intake category (T3 vs. T1: β: 1.4 ml/min/1.73 m 2 ; 95%CI: 0.5-2.3, β: 1.0; 95%CI: 0.1-2.0, respectively)., Conclusions: Plain water rather than other water sources, and especially tap water, was associated with lower kidney function decline assessed through eGFR over 3-years of follow-up, in older individuals at high cardiovascular risk., Trial Registration: ISRCTN89898870. Retrospectively registered on 24 July 2014., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The relationship between premature ovarian insufficiency (FXPOI) and premutation in the FMR1 gene is well established. In recent years, though, a potential relationship between the latter and a low ovarian reserve has been suggested. To explore it, we conducted a retrospective study in an IVF program at a university tertiary referral center in Barcelona (Spain). Data were obtained retrospectively from a total of 385 women referred for FMR1 gene testing at our institution from January 2018 to December 2021. We compared the prevalence of FMR1 gene premutation between 93 of them, younger than 35 years, with a diminished ovarian reserve (DOR), characterized by levels of anti-Mullerian hormone < 1.1 ng/mL and antral follicle count < 5; and 132 egg donors screened by protocol that served as the controls. We found a higher prevalence of FMR1 premutation in the DOR group (seven patients (7.69%)) than in the control group (one patient (1.32%)), Fisher-exact test p -value = 0.012). We concluded that compared with the general population represented by young egg donors, the prevalence of FMR1 gene premutation is higher in young patients with a diminished ovarian reserve. Although these findings warrant further prospective validation in a larger cohort of patients within DOR, they suggest that, in clinical practice, FMR1 premutation should be determined in infertile young patients with DOR in order to give them adequate genetic counselling.

Background: The COVID-19 lockdown represented an immense impact on human health, which was characterized by lifestyle and dietary changes, social distancing and isolation at home. Some evidence suggests that these consequences mainly affected women and altered relevant ongoing clinical trials. The aim of this study was to evaluate the status and changes in diet, physical activity (PA), sleep and self-reported health status (SRH) as perceived by older adult men and women with metabolic syndrome during the COVID-19 lockdown., Methods: We analyzed data from 4681 Spanish adults with metabolic syndrome. We carried out a telephone survey during May and June 2020 to collect information on demographics, dietary habits, PA, sleep, SRH and anthropometric data., Results: The mean age of participants was 64.9 years at recruitment, and 52% of participants were men. Most participants (64.1%) perceived a decrease in their PA during confinement. Regarding gender-specific differences, a higher proportion of women than men perceived a decrease in their PA (67.5% vs. 61.1%), Mediterranean diet adherence (20.9% vs. 16.8%), sleep hours (30.3% vs. 19.1%), sleep quality (31.6% vs. 18.2%) and SRH (25.9% vs. 11.9%) (all p < 0.001)., Conclusions: The COVID-19 lockdown affected women more negatively, particularly their self-reported diet, PA, sleep and health status.

Background: There has been a substantial increase in the use of laparoscopic sleeve gastrectomy (SG) to treat morbid obesity despite observational evidence demonstrating the superiority of Roux-en-Y gastric bypass (RYGB) for reducing low-density lipoprotein (LDL) cholesterol. The main aim was to ascertain whether high LDL cholesterol levels should be considered when selecting the most appropriate surgical procedure for each patient (RYGB or SG)., Methods: In this single-center, randomized clinical trial using intention-to-treat analysis, 38 patients with severe obesity and elevated levels of LDL cholesterol were randomly assigned to undergo RYGB or SG. The primary outcome was LDL cholesterol remission at 12 months, defined as LDL cholesterol < 3.36 nmol/l without lipid-lowering medications. Secondary outcomes included changes in weight, other comorbidities, qualitative lipoprotein traits, cholesterol esters, glycoproteins, cholesterol absorption and synthesis metabolites and complications., Results: Intention-to-treat analysis revealed that LDL cholesterol remission occurred in 66.6% of RYGB patients compared to 27.8% of SG patients (p = 0.019). Among patients completing follow-up, RYGB demonstrated superior remission (80.0% vs. 29.4%, p = 0.005). Exclusive benefits of RYGB included a reduction in large, medium, and small LDL particles. Cholesterol absorption markers showed differential behavior after both techniques: campesterol (Δ -15.2 µg/mg, 95% CI -30.2 to -0.1) decreased after RYGB, and sitosterol (Δ 21.1 µg/mg, 95% CI 0.9 to 41.2), cholestanol (Δ 30.6 µg/mg, 95% CI 14.8 to 57.9) and campesterol (Δ 18.4 µg/mg, 95% CI 4.4 to 32.3) increased after SG. No differences in weight loss, cholesterol esters, glycoproteins, cholesterol synthesis metabolites or postoperative complications were observed between techniques., Conclusion: In conclusion, RYGB is superior to SG in terms of short-term of high LDL cholesterol remission. Furthermore, RYGB also led to a greater improvement in lipoprotein parameters that confer an atherogenic profile. Therefore, the presence of elevated levels of LDL cholesterol should be considered when determining the optimal bariatric surgery procedure for each patient., Trial Registration: Clinicaltrials.gov number, NCT03975478)., (© 2024. The Author(s).)

Background: The Mediterranean diet (MedDiet) has demonstrated efficacy in preventing age-related cognitive decline and modulating plasma concentrations of endocannabinoids (eCBs) and N-acylethanolamines (NAEs, or eCB-like compounds), which are lipid mediators involved in multiple neurological disorders and metabolic processes. Hypothesizing that eCBs and NAEs will be biomarkers of a MedDiet intervention and will be related to the cognitive response, we investigated this relationship according to sex and apolipoprotein E (APOE) genotype, which may affect eCBs and cognitive performance., Methods: This was a prospective cohort study of 102 participants (53.9% women, 18.8% APOE-ɛ4 carriers, aged 65.6 ± 4.5 years) from the PREDIMED-Plus-Cognition substudy, who were recruited at the Hospital del Mar Research Institute (Barcelona). All of them presented metabolic syndrome plus overweight/obesity (inclusion criteria of the PREDIMED-Plus) and normal cognitive performance at baseline (inclusion criteria of this substudy). A comprehensive battery of neuropsychological tests was administered at baseline and after 1 and 3 years. Plasma concentrations of eCBs and NAEs, including 2-arachidonoylglycerol (2-AG), anandamide (AEA), oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and N-docosahexaenoylethanolamine (DHEA), were also monitored. Baseline cognition, cognitive changes, and the association between eCBs/NAEs and cognition were evaluated according to gender (crude models), sex (adjusted models), and APOE genotype., Results: At baseline, men had better executive function and global cognition than women (the effect size of gender differences was - 0.49, p = 0.015; and - 0.42, p = 0.036); however, these differences became nonsignificant in models of sex differences. After 3 years of MedDiet intervention, participants exhibited modest improvements in memory and global cognition. However, greater memory changes were observed in men than in women (Cohen's d of 0.40 vs. 0.25; p = 0.017). In men and APOE-ε4 carriers, 2-AG concentrations were inversely associated with baseline cognition and cognitive changes, while in women, cognitive changes were positively linked to changes in DHEA and the DHEA/AEA ratio. In men, changes in the OEA/AEA and OEA/PEA ratios were positively associated with cognitive changes., Conclusions: The MedDiet improved participants' cognitive performance but the effect size was small and negatively influenced by female sex. Changes in 2-AG, DHEA, the OEA/AEA, the OEA/PEA and the DHEA/AEA ratios were associated with cognitive changes in a sex- and APOE-dependent fashion. These results support the modulation of the endocannabinoid system as a potential therapeutic approach to prevent cognitive decline in at-risk populations., Trial Registration: ISRCTN89898870., (© 2024. The Author(s).)

Background: Fragile X-associated primary ovarian insufficiency (FXPOI), characterized by amenorrhea before age 40 years, occurs in 20% of female FMR1 premutation carriers. Presently, there are no molecular or biomarkers that can help predicting which FMR1 premutation women will develop FXPOI. We previously demonstrated that high FMR4 levels can discriminate between FMR1 premutation carriers with and without FXPOI. In the present study the relationship between the expression levels of FMR4 and the ovarian reserve markers was assessed in female FMR1 premutation carriers under age of 35 years., Methods: We examined the association between FMR4 transcript levels and the measures of total antral follicle count (AFC) and serum anti-müllerian hormone (AMH) levels as markers of ovarian follicle reserve., Results: Results revealed a negative association between FMR4 levels and AMH (r = 0.45) and AFC (r = 0.64). Statistically significant higher FMR4 transcript levels were found among those FMR1 premutation women with both, low AFCs and AMH levels., Conclusions: These findings reinforce previous studies supporting the association between high levels of FMR4 and the risk of developing FXPOI in FMR1 premutation carriers., (© 2024. The Author(s).)

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 [β-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/m 2 (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., 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 © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: To assess the effects of Helicobacter pylori (HP) eradication with an omeprazole, clarithromycin, amoxicillin, and metronidazole (OCAM) regimen on the metabolic profile and weight loss 12 months after bariatric surgery (BS)., Methods: Retrospective analysis of a prospective cohort of patients with morbid obesity undergoing BS. HP presence was tested preoperatively by gastric biopsy and treated with OCAM when positive. Short-term metabolic outcomes and weight loss were evaluated., Results: HP infection was detected in 75 (45.7%) of the 164 patients included. OCAM effectiveness was 90.1%. HP-negative patients had a greater reduction in glucose levels at 3 (-14.6 ± 27.5 mg/dL HP-treated vs -22.0 ± 37.1 mg/dL HP-negative, p=0.045) and 6 months (-13.7 ± 29.4 mg/dL HP-treated vs -26.4 ± 42.6 mg/dL HP-negative, p= 0.021) and greater total weight loss (%TWL) at 6 (28.7 ± 6.7% HP-treated vs 30.45 ± 6.48% HP-negative, p= 0.04) and 12 months (32.21 ± 8.11% HP-treated vs 35.14 ± 8.63% HP-negative, p= 0.023)., Conclusions: Preoperative treatment with OCAM has been associated to poorer glycemic and weight loss outcomes after BS. More research is needed on the influence of OCAM on gut microbiota, and in turn, the effect of the latter on metabolic and weight loss outcomes after BS., (© 2024. The Author(s).)

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 β = 0.65 points, 95% confidence interval (CI) 0.15-1.15; p = 0.011]. This association was particularly prominent in women ( β = 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.

Psoriasis and hidradenitis suppurativa are often associated with obesity. Because chronic low-grade inflammation underlies these 2 diseases, they can progress to more severe forms in patients with obesity if weight-reduction measures are not taken. This review covers pharmacologic alternatives for treating obesity, with emphasis on the benefits associated with the novel use of glucagon-like peptide-1 (GLP-1) agonists that act on satiety receptors. These drugs have led to greater weight loss in clinical trials and real-world settings than orlistat, which until recently was the only drug approved for treating obesity in the European Union. Although experience with GLP-1 agonists in patients with obesity and inflammatory skin diseases is currently scarce, the promising results reported suggest they may offer a useful tool for managing obesity., (Copyright © 2023 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

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 (β: -3.39 ml/min/1.73 m 2 ; 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 (β: -1.45 ml/min/1.73 m 2 ; 95% CI: -2.90 to -0.01) as well as after 3-years of follow-up (β: -2.18 ml/min/1.73 m 2 ; 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., Competing Interests: Conflict of interest JS-S reported receiving research support from the California Walnut Commission, Patrimonio Comunal Olivarero, La Morella Nuts, and Borges S.A; receiving consulting fees or travel expenses from Instituto Danone, Abbott Laboratories and Mundifarma, receiving nonfinancial support from Hojiblanca, Patrimonio Comunal Olivarero, and Almond Board of California; serving on the board of and receiving grant support through his institution from the International Nut and Dried Foundation and the Eroski Foundation. All other authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: A major barrier to a healthy diet may be the higher price of healthy foods compared to low-quality foods., Objectives: This study aimed to assess the association between the monetary cost of food and diet quality in Spanish older adults at high risk of cardiovascular disease., Methods: Cross-sectional analysis was carried out in Spanish older adults ( n = 6,838; 48.6% female). A validated food frequency questionnaire was used to assess dietary intake. Metabolic syndrome severity, adherence to the Mediterranean diet (MedDiet), adherence to a provegetarian dietary pattern, and dietary inflammatory index were assessed. The economic cost of the foods was obtained from the Spanish Ministry of Agriculture Fisheries and Food database (2015-2017, the period of time when the participants were recruited). The total cost of diet adjusted per 1,000 kcal was computed., Results: The healthier dietary pattern was associated with a higher cost of the diet. Higher adherence to the MedDiet, anti-inflammatory diet, and the healthy version of the provegetarian dietary pattern were related to higher costs of the diet., Conclusion: Higher diet quality was associated with a higher dietary cost of the diet per 1,000 kcal/day. Food prices can be an important component of interventions and policies aimed at improving people's diets and preventing diet-related chronic diseases., Clinical Trial Registry Number: The trial was registered in 2014 at the International Standard Randomized Controlled Trial (ISRCT; http://www.isrctn.com/ISRCTN89898870) with the number 89898870., Competing Interests: JS-S reports serving on the board of and receiving grant support through his institution from the International Nut and Dried Fruit Council, and Eroski Foundation. Reports serving in the Executive Committee of the Instituto Danone Spain and on the Scientific Committee of the Danone International Institute. He has received research support from Patrimonio Comunal Olivarero, Spain and Borges SA, Spain. Reports receiving consulting fees or travel expenses from Danone; Eroski Foundation, Instituto Danone, Spain, and Abbot Laboratories. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer MM-A declared a shared affiliation with the author BR-G to the handling editor at the time of review., (Copyright © 2023 Bouzas, Pastor, García, Monserrat-Mesquida, Martínez-González, Salas-Salvadó, Corella, Schröder, Martínez, Alonso-Gómez, Wärnberg, Vioque, Romaguera, Lopez-Miranda, Estruch, Tinahones, Lapetra, Serra-Majem, Riquelme-Gallego, Romero-Secin, Pintó, Gaforio, Matía, Vidal, Zapatero, Daimiel, Ros, García-Arellano, Babio, Gonzalez-Monje, Castañer, Abete, Tojal-Sierra, Benavente-Marín, Signes-Pastor, Konieczna, García-Ríos, Castro-Barquero, Fernández-García, Santos-Lozano, Bes-Rastrollo, Mestres, Guillem-Saiz, Goday, Goicolea-Güemez, Puig-Aguiló, Ruiz-Canela, Palau-Galindo, Fitó and Tur.)

Background: Metabolic syndrome (MetS) has become a growing risk factor of some non-communicable diseases. Increase of greenhouse gas emissions affects the planet., Aims: To assess the association between MetS severity and amount of carbon dioxide (CO 2 ) emitted in an adult population., Design: Cross-sectional study (n = 6646; 55-76-year-old-men; 60-75-year-old-women with MetS)., Methods: Dietary habits were assessed using a pre-validated semi quantitative 143-item food frequency questionnaire. The amount of CO 2 emitted due to the production of food consumed by person and day was calculated using a European database, and the severity of the MetS was calculated with the MetS Severity Score., Results: Higher glycaemia levels were found in people with higher CO 2 emissions. The risk of having high severe MetS was related to high CO 2 emissions., Conclusions: Low CO 2 emissions diet would help to reduce MetS severity. Advantages for both health and the environment were found following a more sustainable diet., Trial Registration: ISRCTN, ISRCTN89898870 . Registered 05 September 2013., (© 2023. The Author(s).)

Introduction: The principal source of exposure to Polychlorinated dibenzo-p-dioxins and polychlorinated dibenzo-p-furans (PCDD/Fs) in humans comes from food intake. PCDD/Fs, are a family of potential endocrine disruptors and have been associated with different chronic diseases such as diabetes and hypertension. However, studies assessing the relationship between dietary exposure to PCDD/Fs and adiposity or obesity status in a middle-aged population are limited., Objective: To assess cross-sectionally and longitudinally the associations between estimated dietary intake (DI) of PCDD/Fs and body mass index (BMI), waist circumference, and the prevalence/incidence of obesity and abdominal obesity in a middle-aged population., Methods: In 5899 participants aged 55-75 years (48% women) living with overweight/obesity from the PREDIMED-plus cohort, PCDD/Fs DI was estimated using a 143-item validated food-frequency questionnaire, and the levels of food PCDD/F expressed as Toxic Equivalents (TEQ). Consequently, cross-sectional and prospective associations between baseline PCDD/Fs DI (in pgTEQ/week) and adiposity or obesity status were assessed at baseline and after 1-year follow-up using multivariable cox, logistic or linear regression models., Results: Compared to participants in the first PCDD/F DI tertile, those in the highest tertile presented a higher BMI (β-coefficient [confidence interval]) (0.43kg/m2 [0.22; 0.64]; P-trend <0.001), a higher waist circumference (1.11 cm [0.55; 1.66]; P-trend <0.001), and a higher prevalence of obesity and abdominal obesity (1.05 [1.01; 1.09] and 1.02 [1.00; 1.03]; P-trend = 0.09 and 0.027, respectively). In the prospective analysis, participants in the top PCDD/F DI baseline tertile showed an increase in waist circumference compared with those in the first tertile after 1-year of follow-up (β-coefficient 0.37 cm [0.06; 0.70]; P-trend = 0.015)., Conclusion: Higher DI of PCDD/Fs was positively associated with adiposity parameters and obesity status at baseline and with changes in waist circumference after 1-year of follow-up in subjects living with overweight/obesity. Further large prospective studies using a different population with longer follow-up periods are warranted in the future to strengthen our results., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Adipose tissue from pheochromocytoma patients acquires brown fat features, making it a valuable model for studying the mechanisms that control thermogenic adipose plasticity in humans. Transcriptomic analyses revealed a massive downregulation of splicing machinery components and splicing regulatory factors in browned adipose tissue from patients, with upregulation of a few genes encoding RNA-binding proteins potentially involved in splicing regulation. These changes were also observed in cell culture models of human brown adipocyte differentiation, confirming a potential involvement of splicing in the cell-autonomous control of adipose browning. The coordinated changes in splicing are associated with a profound modification in the expression levels of splicing-driven transcript isoforms for genes involved in the specialized metabolism of brown adipocytes and those encoding master transcriptional regulators of adipose browning. Splicing control appears to be a relevant component of the coordinated gene expression changes that allow human adipose tissue to acquire a brown phenotype., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)

Aims: To assess the comparative effects of glucagon-like peptide-1 receptor agonists (GLP-1RA), 4-dipeptidyl peptidase inhibitors (DPP-4I), and metformin treatment during one year on metabolic syndrome (MetS) components and severity in MetS patients., Methods: Prospective study (n = 6165 adults) within the frame of PREDIMED-Plus trial. The major end-point was changes on MetS components and severity after one- year treatment of GLP-1RA, DPP-4I, and metformin. Anthropometric measurements (weight, height and waist circumference), body mass index (BM), and blood pressure were registered. Blood samples were collected after overnight fasting. Plasma glucose, glycosylated hemoglobin (HbA1c), plasma triglycerides and cholesterol were measured. Dietary intakes as well as physical activity were assessed through validated questionnaires., Results: MetS parameters improved through time. The treated groups improved glycaemia compared with untreated (glycaemia ∆ untreated: -1.7 mg/dL(± 13.5); ∆ metformin: - 2.5(± 23.9) mg/dL; ∆ DPP-4I: - 4.5(± 42.6); mg/dL ∆ GLP-1RA: - 4.3(± 50.9) mg/dL; and HbA1c: ∆ untreated: 0.0(± 0.3) %; ∆ metformin: - 0.1(± 0.7) %; ∆ DPP-4I: - 0.1(± 1.0) %; ∆ GLP-1RA: - 0.2(± 1.2) %. Participants decreased BMI and waist circumference. GLP-1RA and DPP-4I participants registered the lowest decrease in BMI (∆ untreated: -0.8(± 1.6) kg/m 2 ; ∆ metformin: - 0.8(± 1.5) kg/m 2 ; ∆ DPP-4I: - 0.6(± 1.3) kg/m 2 ; ∆ GLP-1RA: - 0.5(± 1.2) kg/m 2 . and their waist circumference (∆ untreated: -2.8(± 5.2) cm; ∆ metformin: - 2.6(± 15.2) cm; ∆ DPP-4I: - 2.1(± 4.8) cm; ∆ GLP-1RA: - 2.4(± 4.1) cm., Conclusion: In patients with MetS and healthy lifestyle intervention, those treated with GLP-1RA and DPP-4I obtained better glycemic profile. Anthropometric improvements were modest., Competing Interests: Conflict of interest statement JS-S reports serving on the board of and receiving grant support through his institution from the International Nut and Dried Fruit Council, and Eroski Foundation. Reports serving in the Executive Committee of the Instituto Danone Spain and on the Scientific Committee of the Danone International Institute. He has received research support from Patrimonio Comunal Olivarero, Spain; and Borges S.A., Spain. Reports receiving consulting fees or travel expenses from Danone; Eroski Foundation, Instituto Danone - Spain, and Abbot Laboratories., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The main objective of this work was to explore the association of dietary phytate intake with bone mineral density (BMD) in a Mediterranean population of postmenopausal women. For this purpose, a cross-sectional analysis of 561 women aged 55-75 years with overweight/obesity and metabolic syndrome from a Mediterranean area and with data on dual-energy X-ray absorptiometry (DXA) scans in femur and lumbar spine was performed. Estimated phytate intake was calculated using a validated food frequency questionnaire. Our results indicated that phytate intake was associated with BMD [β(95%CI) per each 25 mg/100 kcal] in femoral neck [0.023(0.060-0.040) g/cm 2 ], femoral Ward's triangle [0.033(0.013-0.054) g/cm 2 ], total femur [0.018(0.001-0.035) g/cm 2 ], and all the analyzed lumbar spine sites [L1-L4: 0.033(0.007-0.059) g/cm 2 ] after adjusting for potential confounders. The sensitivity analysis showed that phytate intake was directly associated with lumbar spine BMD in women younger than 66 years, with a body mass index higher than 32.6 kg/cm 2 and without type 2 diabetes (all p -for interactions < 0.05). The overall results indicated that phytate, a substance present in food as cereals, legumes and nuts, was positively associated with BMD in Mediterranean postmenopausal women. Phytate may have a protective effect on bone resorption by adsorbing on the surfaces of HAP. Nevertheless, large, long-term, and randomized prospective clinical studies must be performed to assess the possible benefits of phytate consumption on BMD in postmenopausal women.

Background: The COVID-19 pandemic has affected the implementation of most ongoing clinical trials worldwide including the PREDIMED-Plus study. The PREDIMED-Plus is an ongoing, multicenter, controlled intervention trial, aimed at weight-loss and cardiovascular disease prevention, in which participants were randomized (1:1 ratio) to an intervention group (energy-reduced Mediterranean diet, promotion of physical activity, and behavioral support) or to a control group (Mediterranean diet with usual care advice). When the pandemic began, the trial was in the midst of the planned intervention. The objective of this report was to examine the effects of the pandemic on the delivery of the intervention and to describe the strategies established to mitigate the possible adverse effects of the pandemic lockdown on data collection and adiposity., Methods: We assessed the integrity of the PREDIMED-Plus trial during 5 identified periods of the COVID-19 pandemic determined according to restrictions dictated by the Spanish government authorities. A standardized questionnaire was delivered to each of the 23 PREDIMED-Plus recruiting centers to collected data regarding the trial integrity. The effect of the restrictions on intervention components (diet, physical activity) was evaluated with data obtained in the three identified lockdown phases: pre lockdown, lockdown proper, and post lockdown., Results: During the lockdown (March/2020-June/2021), 4,612 participants (48% women, mean age 65y) attended pre-specified yearly follow-up visits to receive lifestyle recommendations and obtain adiposity measures. The overall mean (SD) of the proportions reported by each center showed that 40.4% (25.4) participants had in-person visits, 39.8% (18.2) participants were contacted by telephone and 35% (26.3) by electronic means. Participants' follow-up and data collection rates increased across lockdown periods (from ≈10% at onset to ≈80% at the end). Compared to pre-lockdown, waist circumference increased during (0.75 cm [95% CI: 0.60-0.91]) and after (0.72 cm [95% CI: 0.56-0.89]) lockdown. Body weight did not change during lockdown (0.01 kg [95% CI: -0.10 to 0.13) and decreased after lockdown (-0.17 kg [95% CI: -0.30 to -0.04])., Conclusion: Mitigating strategies to enforce the intervention and patient's follow-up during lockdown have been successful in preserving the integrity of the trial and ensuring its continuation, with minor effects on adiposity., Clinical Trial Registration: https://doi.org/10.1186/ISRCTN89898870, identifier ISRCTN89898870., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Paz-Graniel, Fitó, Ros, Buil-Cosiales, Corella, Babio, Martínez, Alonso-Gómez, Wärnberg, Vioque, Romaguera, López-Miranda, Estruch, Tinahones, Lapetra, Serra-Majem, Bueno-Cavanillas, Tur, Martín-Sánchez, Pintó, Gaforio, Matía-Martín, Vidal, Vázquez, Daimiel, García-Gavilán, Toledo, Nishi, Sorlí, Castañer, García-Ríos, García de la Hera, Barón-López, Ruiz-Canela, Morey, Casas, Garrido-Garrido, Tojal-Sierra, Fernández-García, Vázquez-Ruiz, Fernández-Carrión, Goday, Peña-Orihuela, Compañ-Gabucio, Schröder, Martínez-Gonzalez and Salas-Salvadó.)

Background: Research related to sustainable diets is is highly relevant to provide better understanding of the impact of dietary intake on the health and the environment., Aim: To assess the association between the adherence to an energy-restricted Mediterranean diet and the amount of CO 2 emitted in an older adult population., Design and Population: Using a cross-sectional design, the association between the adherence to an energy-reduced Mediterranean Diet (erMedDiet) score and dietary CO 2 emissions in 6646 participants was assessed., Methods: Food intake and adherence to the erMedDiet was assessed using validated food frequency questionnaire and 17-item Mediterranean questionnaire. Sociodemographic characteristics were documented. Environmental impact was calculated through greenhouse gas emissions estimations, specifically CO 2 emissions of each participant diet per day, using a European database. Participants were distributed in quartiles according to their estimated CO 2 emissions expressed in kg/day: Q1 (≤2.01 kg CO 2 ), Q2 (2.02-2.34 kg CO 2 ), Q3 (2.35-2.79 kg CO 2 ) and Q4 (≥2.80 kg CO 2 )., Results: More men than women induced higher dietary levels of CO 2 emissions. Participants reporting higher consumption of vegetables, fruits, legumes, nuts, whole cereals, preferring white meat, and having less consumption of red meat were mostly emitting less kg of CO 2 through diet. Participants with higher adherence to the Mediterranean Diet showed lower odds for dietary CO 2 emissions: Q2 (OR 0.87; 95%CI: 0.76-1.00), Q3 (OR 0.69; 95%CI: 0.69-0.79) and Q4 (OR 0.48; 95%CI: 0.42-0.55) vs Q1 (reference)., Conclusions: The Mediterranean diet can be environmentally protective since the higher the adherence to the Mediterranean diet, the lower total dietary CO 2 emissions. Mediterranean Diet index may be used as a pollution level index., (© 2023. The Author(s).)

Objectives: We tested the effects of a weight-loss intervention encouraging energy-reduced MedDiet and physical activity (PA) in comparison to ad libitum MedDiet on COVID-19 incidence in older adults., Design: Secondary analysis of PREDIMED-Plus, a prospective, ongoing, multicentre randomized controlled trial., Setting: Community-dwelling, free-living participants in PREDIMED-Plus trial., Participants: 6,874 Spanish older adults (55-75 years, 49% women) with overweight/obesity and metabolic syndrome., Intervention: Participants were randomised to Intervention (IG) or Control (CG) Group. IG received intensive behavioural intervention for weight loss with an energy-reduced MedDiet intervention and PA promotion. CG was encouraged to consume ad libitum MedDiet without PA recommendations., Measurements: COVID-19 was ascertained by an independent Event Committee until December 31, 2021. COX regression models compared the effect of PREDIMED-Plus interventions on COVID-19 risk., Results: Overall, 653 COVID-19 incident cases were documented (IG:317; CG:336) over a median (IQR) follow-up of 5.8 (1.3) years (inclusive of 4.0 (1.2) years before community transmission of COVID-19) in both groups. A significantly lowered risk of COVID-19 incidence was not evident in IG, compared to CG (fully-adjusted HR (95% CI): 0.96 (0.81,1.12))., Conclusions: There was no evidence to show that an intensive weight-loss intervention encouraging energy-reduced MedDiet and PA significantly lowered COVID-19 risk in older adults with overweight/obesity and metabolic syndrome in comparison to ad libitum MedDiet. Recommendations to improve adherence to MedDiet provided with or without lifestyle modification suggestions for weight loss may have similar effects in protecting against COVID-19 risk in older adults with high cardiovascular risks., Competing Interests: Fernandez-Aranda acknowledges consulting fees from Novo Nordisk and Wiley as EIC for the European Eat Dis Rev. He has also received honoraria for lectures and support for travel/meetings from Novo Nordisk. He discloses his honorary participation in the Data Safety Monitoring Board or Advisory Board of Sustain-Consortium-Germany. Emilio Ros has received honoraria for presentations and support for attending meetings/travel from the California Walnut Commission, Alexion and the Spanish Atherosclerosis Society. He has also received consulting fees from Alexion. He participates in the Data Safety Monitoring Board or Advisory Board of the PREDIMED-Plus Clinical Trial. Ramon Estruch has received research grants from Instituto de Salud Carlos III, Madrid, Spain. He has received honoraria for presentations from Fundacion Cerveza y Salud, Spain; Instituto Cervantes, Albuquerque, USA; Instituto Cervantes, Milan, Italy; Instituto Cervantes, Tokyo, Japan; Fundacion Bosch i Gimpera, Spain; Wine and Culinary International Forum; Pernaud Richart; Mexico; Fundacion Dieta Mediterranea, Barcelona, Spain. He has received support for travel or meetings or conference organization from ERAB, Belgium, Brewers of Europe, Belgium, and Sociedad Española de Nutrición (SEN). He has served on the Advisory Board of Cerveza y Salud, Spain. Jordi Salas-Salvadó reported receiving consulting fees from Eroski Foundation. He has also received grants and support for attending meetings/travel from Nut and Dried Fruit Foundation. He is an honorary Member of the International Advisory Board of the Project “Effect of cashew nut supplementation on glycemic status and lipid profile in type 2 diabetes subjects”, Member of the Scientific Advisory Committee of the European PEGASO project (Personalized Guidance Services for Optimizing lifestyle management in teenagers through awareness, motivation and engagement) and Member of the Scientific Committee of Danone Institute International. He received personal fees for serving as a Member of the Institute Danone Advisory Board. Sangeetha Shyam has received consulting fees from Abbott Sdn Bhd. Stephanie K. Nishi is a volunteer member of Plant-Based Canada, a non-profit organization. Other authors (Jesús Francisco García-Gavilán, Indira Paz-Graniel, José J Gaforio4 Miguel Ángel Martínez-González, Dolores Corella, J. Alfredo Martínez, Ángel M. Alonso-Gómez, Julia Wärnberg, Jesús Vioque, Dora Romaguera, José López-Miranda, Francisco J Tinahones, José Lapetra, J. Luís Serra-Majem, Aurora Bueno-Cavanillas, Josep A. Tur, Vicente Martín Sánchez, Xavier Pintó, Pilar Matía-Martín, Josep Vidal, María del Mar Alcarria, Lidia Daimiel, Óscar García Regata, Rafael Perez Araluce, Eva M Asensio, Olga Castañer, Antonio Garcia-Rios, Alejandro Oncina-Cánovas, Cristina Bouzas, M. Angeles Zulet, Elena Rayó, Rosa Casas1,16,17, Sandra Martin-Pelaez, Lucas Tojal-Sierra, Bernal-López MR, Silvia Carlos, Jose V.Sorlí, Albert Goday, Patricia J. Peña-Orihuela, Ana Pastor-Morel, Sonia Eguaras, María Dolors Zomeño, Miguel Delgado-Rodríguez, Nancy Babio, and Montserrat Fitó) declared no potential conflict of interest.

To evaluate the changes in the gut microbiota associated with changes in the biochemical markers of nonalcoholic fatty liver disease (NAFLD) after a lifestyle intervention with the Mediterranean diet. Participants ( n  = 297) from two centers of PREDIMED-Plus trial (Prevención con Dieta Mediterránea) were divided into three different groups based on the change tertile in the Hepatic Steatosis Index (HSI) or the Fibrosis-4 score (FIB-4) between baseline and one year of intervention. One-year changes in HSI were: tertile 1 (T1) (-24.9 to -7.51), T2 (-7.5 to -1.86), T3 (-1.85 to 13.64). The most significant differences in gut microbiota within the year of intervention were observed in the T1 and T3. According to the FIB-4, participants were categorized in non-suspected fibrosis (NSF) and with indeterminate or suspected fibrosis (SF). NSF participants showed higher abundances of Alcaligenaceae , Bacteroidaceae , Bifidobacteriaceae , Clostridiaceae , Enterobacteriaceae , Peptostreptococcaceae , Verrucomicrobiaceae compared to those with SF. Then, participants were divided depending on the FIB-4 tertile of change: T1 (-89.60 to -5.57), T2 (-5.56 to 11.4), and T3 (11.41 to 206.24). FIB-4 T1 showed a decrease in Akkermansia and an increase in Desulfovibrio . T2 had an increase in Victivallaceae , Clostridiaceae , and Desulfovibrio . T3 showed a decrease in Enterobacteriaceae , and an increase in Sutterella , Faecalibacterium , and Blautia . A relation between biochemical index changes of NAFLD/NASH (HSI and FIB-4) and gut microbiota changes were found. These observations highlight the importance of lifestyle intervention in the modulation of gut microbiota and the management of metabolic syndrome and its hepatic manifestations.

Background: Choline and betaine intakes have been related to cardiovascular health., Objectives: We aimed to explore the relation between 1-y changes in dietary intake of choline or betaine and 1-y changes in cardiometabolic and renal function traits within the frame of the PREDIMED (PREvención con DIeta MEDiterránea)-Plus trial., Methods: We used baseline and 1-y follow-up data from 5613 participants (48.2% female and 51.8% male; mean ± SD age: 65.01 ± 4.91 y) to assess cardiometabolic traits, and 3367 participants to assess renal function, of the Spanish PREDIMED-Plus trial. Participants met ≥3 criteria of metabolic syndrome and had overweight or obesity [BMI (in kg/m2) ≥27 and ≤40]. These criteria were similar to those of the PREDIMED parent study. Dietary intakes of choline and betaine were estimated from the FFQ., Results: The greatest 1-y increase in dietary choline or betaine intake (quartile 4) was associated with improved serum glucose concentrations (-3.39 and -2.72 mg/dL for choline and betaine, respectively) and HbA1c levels (-0.10% for quartile 4 of either choline or betaine intake increase). Other significant changes associated with the greatest increase in choline or betaine intake were reduced body weight (-2.93 and -2.78 kg, respectively), BMI (-1.05 and -0.99, respectively), waist circumference (-3.37 and -3.26 cm, respectively), total cholesterol (-4.74 and -4.52 mg/dL, respectively), and LDL cholesterol (-4.30 and -4.16 mg/dL, respectively). Urine creatinine was reduced in quartile 4 of 1-y increase in choline or betaine intake (-5.42 and -5.74 mg/dL, respectively)., Conclusions: Increases in dietary choline or betaine intakes were longitudinally related to improvements in cardiometabolic parameters. Markers of renal function were also slightly improved, and they require further investigation.This trial was registered at https://www.isrctn.com/ as ISRCTN89898870., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Introduction: Obesity, an increasing global health problem, can affect people with other disease conditions. The prevalence of obesity in people with type 1 diabetes (T1D) is not well known. The aim of this study was to describe extensively the characteristics and prevalence of different classes of obesity according to BMI (body mass index) categories in a large cohort of patients with T1D., Material and Methods: This was a retrospective, cross-sectional study in Catalonia. We reviewed all patients with T1D diagnosis, ≥ 18 years old and with BMI data from the SIDIAP database. Sociodemographic and clinical data, cardiovascular risk factors, laboratory parameters and concomitant medications were collected., Results: A total of 6,068 patients with T1D were analyzed. The prevalence of obesity in the total sample was 18% (13.8% with class 1 obesity [BMI 30-34.9 kg/m2]). Patients with obesity had a higher prevalence of other cardiovascular risk factors (i.e. hypertension was 61.4% vs. 37.5%; dyslipidemia 63.6% vs 44%, and chronic kidney disease 38.4% vs. 24.4%; p<0.001 in all cases) and poorer control of them. The higher prevalence was regardless of sex, age and duration of diabetes. The increase in these comorbidities was noticeable from a BMI > 25 kg/m2. Patients with obesity did not have poorer glycemic control., Conclusion: The presence of obesity in people with T1D is frequent and cardiovascular risk factors are more common and more poorly controlled in T1D patients with obesity., Competing Interests: IG received support for attending meetings form Boehringer Ingelheim, Lilly, MSD, Novo-Nordisk and Sanofi. JF-N received advisory and/or speaking fees from Astra-Zeneca, Ascensia, Boehringer Ingelheim, GSK, Lilly, MSD, Novartis, Novo Nordisk and Sanofi. Received research grants to the institution from Astra-Zeneca. GSK, Lilly, MSD, Novartis, Novo Nordisk, Sanofi and Boehringer. DM has received advisory and/or speaking fees from Almirall, Esteve, Ferrer, Janssen, Lilly, Menarini, MSD, NovoNordisk and Sanofi. GG-P has received speaking fees from Lilly and Astra-Zeneca. MM-C has received advisory honorarium from for Astra-Zeneca, Bayer, Boehringer Ingelheim, GSK, Lilly, MSD, NOVARTIS, NovoNordisk, Sanofi; speaker honorarium from Astra- Zeneca, Bayer, Boehringer Ingelheim, GSK, Lilly, Menarini, MSD, Novartis, NovoNordisk, and Sanofi; and research grants to institution from Astra-Zeneca, GSK, Lilly, MSD, Novartis, NovoNordisk, and Sanofi. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Genua, Franch-Nadal, Navas, Mata-Cases, Giménez-Pérez, Vlacho, Mauricio and Goday.)

Background: Obesity is produced by the enlargement of the adipose tissue. Functioning as an endocrine organ, it releases and receives information through a complex network of cytokines, hormones, and substrates contributing to a low-chronic inflammation environment. Diet and healthy habits play key roles in the prevention of obesity and its related pathologies. In this regard, there is a need to switch to healthier and more appetizing diets, such as the Mediterranean one., Objective: To compare the mid-and long-term effects of two Mediterranean diet (MedDiet) interventions, one energy-reduced plus physical activity promotion versus a non-restrictive diet, on peripheral satiety-related hormones, weight loss, glucose/lipid metabolism, and pro-inflammatory markers in subjects with obesity/overweight and metabolic syndrome., Materials and Methods: A randomized, lifestyle intervention was conducted in 23 Spanish centers, with a large cohort of patients presenting metabolic syndrome. Our study is a subproject set in IMIM (Hospital del Mar Research Institute). Participants were men and women, aged 55-75 and 60-75, respectively, who at baseline met at least three metabolic syndrome components. Subjects were assigned to two intervention groups: (1) an intensive lifestyle intervention with an energy-reduced MedDiet and physical activity promotion (intervention group) with the aim of weight loss; and (2) a normocaloric MedDiet (control). We quantified in a subsample of 300 volunteers from Hospital del Mar Research Institute (Barcelona), following analytes at baseline, 6 months, and 1 year: glucose, HbA1c, triglycerides, total cholesterol, high-density lipoprotein cholesterol, LDL cholesterol, C-peptide, ghrelin, GLP-1, glucagon, insulin, leptin, PAI-1, resistin, and visfatin. Anthropometric and classical cardiovascular risk factors were also determined. A multivariate statistical model was employed to compare the two groups. Linear mixed-effect models were performed to compare changes in risk factors and biomarkers between intervention groups and over time., Results: Compared to participants in the control group, those in intervention one showed greater improvements in weight, waist circumference, insulin ( P < 0.001), glucose metabolism-related compounds ( P < 0.05), triglyceride-related lipid profile ( P < 0.05), leptin, blood pressure, and pro-inflammatory markers such as PAI-1 ( P < 0.001) at mid-and/or long-term. High-sensitivity C-reactive protein, resistin, and vifastin also decreased in both groups., Conclusion: A weight loss intervention employing a hypocaloric MedDiet and physical activity promotion has beneficial effects on adiposity, glucose metabolism, lipid profile, leptin, and pro-inflammatory markers, such as PAI-1 in both mid-and long-term., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hernando-Redondo, Toloba, Benaiges, Salas-Salvadó, Martínez-Gonzalez, Corella, Estruch, Tinahones, Ros, Goday, Castañer and Fitó.)

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., (Copyright © 2021 SEEN and SED. Published by Elsevier España, S.L.U. All rights reserved.)

The production and consumption of ultra-processed foods (UPF) has increased considerably during the last years worldwide. Collective evidence shows the association between UPF consumption and adverse health outcomes, including inflammatory gastro-intestinal disorders and obesity. The gut microbiota has been suggested as potential mediator of the effects of UPF consumption on metabolism and health. However, few studies have been conducted in order to elucidate these aspects. Therefore, the aim of the present study was to assess the cross-sectional associations between UPF consumption and gut microbiota in a population of senior subjects ( n = 645) within the frame of the PREDIMED-Plus trial. Eligible participants were men and women (aged 55-75 years), without documented history of cardiovascular disease at enrollment, with overweight/obesity (body mass index ≤ 27 and <40 kg/m 2 ) and metabolic syndrome. Using the information of food frequency questionnaires, the consumption of UPF, expressed as a percentage of total dietary energy intake in kcal/day, was calculated considering those food items classified in group 4 of NOVA system. Population was categorized according to tertiles of UPF consumption. Taxonomic fecal microbiota information, along with blood biochemical parameters, anthropometric measurements and clinical data were obtained. Bioinformatics analysis was performed to study the association between fecal microbiota composition and UPF consumption. We observed that subjects allocated in the highest tertile of UPF consumption (21.4 ± 5.0 % kcal/day) presented lower adherence to MedDiet ( p < 0.001) and higher total energy intake ( p < 0.001). The taxonomic analysis of the fecal microbiota revealed a significant (Benjamini-Hochberg adjusted p < 0.2) positive association between specific taxa and tertiles (T) of UPF consumption: Alloprevotella ( p = 0.041 vs. T2; p = 0.065 vs. T3), Negativibacillus ( p = 0.096 vs. T3), Prevotella ( p = 0.116 vs. T3), and Sutterella ( p = 0.116 vs. T2). UPF consumption was positively associated with lower adherence to MedDiet and higher total energy intake in senior subjects with overweight obesity and metabolic syndrome. In addition, positive association with specific fecal microbiota taxa related to inflammatory gastro-intestinal diseases and low consumption of fruits and vegetables, was observed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Atzeni, Martínez, Babio, Konstanti, Tinahones, Vioque, Corella, Fitó, Vidal, Moreno-Indias, Pertusa-Martinez, Álvarez-Sala, Castañer, Goday, Damas-Fuentes, Belzer, Martínez-Gonzalez, Hu and Salas-Salvadó.)

Non-alcoholic fatty liver disease (NAFLD) includes a spectrum of liver alterations that can result in severe disease and even death. Consumption of ultra-processed foods (UPF) has been associated with obesity and related comorbidities. However, the link between UPF and NAFLD has not been sufficiently assessed. We aimed to investigate the prospective association between UPF consumption and liver health biomarkers. Methods: We followed for 1 year 5867 older participants with overweight/obesity and metabolic syndrome (MetS) from the PREDIMED-Plus trial. A validated 143-item semi-quantitative food frequency questionnaire was used to evaluate consumption of UPF at baseline, 6, and 12 months. The degree of processing for foods and beverages (g/day) was established according to the NOVA classification system. The non-invasive fatty liver index (FLI) and hepatic steatosis index (HSI) were used to evaluate liver health at three points in time. The associations between changes in UPF consumption (percentage of total daily dietary intake (g)) and liver biomarkers were assessed using mixed-effects linear models with repeated measurements. Results: In this cohort, UPF consumption at baseline was 8.19% (SD 6.95%) of total daily dietary intake in grams. In multivariable models, each 10% daily increment in UPF consumption in 1 year was associated with significantly greater FLI (β 1.60 points, 95% CI 1.24;1.96 points) and HSI (0.43, 0.29; 0.57) scores (all p-values < 0.001). These associations persisted statistically significant after adjusting for potential dietary confounders and NAFLD risk factors. Conclusions: A higher UPF consumption was associated with higher levels of NAFLD-related biomarkers in older adults with overweight/obesity and MetS.

Background and Aims: Previous studies have shown beneficial associations between fruit and vegetable (FV) consumption and cardiometabolic risk factors. However, variety in FV, which may play an important role on cardiovascular health due to the different nutrient and phytochemical content among the different groups and subgroups of FV has been poorly investigated. We longitudinally investigated associations between 1-year changes in variety and quantity of FV and concurrent changes in cardiometabolic risk factors in elderly subjects with overweight/obesity and metabolic syndrome., Methods: a one-year data longitudinal analysis of 6647 PREDIMED-plus study participants (48% women) was conducted. Data were collected at baseline, six months and 1-year of follow-up. Variety and quantity of FV were estimated using a food frequency questionnaire and continuous scores for variety were created based on items/month of FV. Linear mixed-models adjusted for potential confounders were performed to estimate associations (β-coefficients and 95% confidence interval) between 1-year changes in FV variety and/or quantity and concurrent changes in cardiometabolic risk factors., Results: Two points increment in the FV variety score over one year was associated with a concurrent decrease in glucose (-0.33 mg/dL (0.58, -0.07)), body weight (-0.07 kg (-0.13, -0.02)) and waist circumference (WC) (-0.08 cm (-0.16, -10.01)). An increment of 100 g/d of FV over one year was associated with a concurrent decrease in triglycerides (-0.50 mg/dL (-0.93, -0.08)), glucose (-0.21 mg/dL (-0.32, -0.11)), body weight (-0.11 kg (-0.15, -0.07)) and WC (-0.10 cm (-0.14, -0.06)) over 1-year. Changes in FV consumption which led to higher quantity and variety over one year were associated with downward changes in glucose (-1.26 mg/dL (-2.09, -0.43)), body weight (-0.40 kg (-0.58, -0.23)) and WC (-0.50 cm (-0.73, -0.28))., Conclusion: Greater variety, in combination with higher quantity of FV was significantly associated with a decrease in several cardiometabolic risk factors among elderly subjects at high cardiovascular risk., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background & Aims: The quality of dietary carbohydrates rather than total carbohydrate intake may determine the accumulation of visceral fat; however, to date, few studies have examined the impact of diet on adiposity using specific imaging techniques. Thus, the aim of this prospective study was to investigate the association between concurrent changes in carbohydrate quality index (CQI) and objectively-quantified adiposity distribution over a year., Methods: We analyzed a cohort of 1476 participants aged 55-75 years with overweight/obesity and metabolic syndrome (MetS) from the PREDIMED-Plus randomized controlled trial. Dietary intake information was obtained at baseline, 6- and 12-months from a validated 143-item semi-quantitative food-frequency questionnaire, and CQI (range: 4 to 20) was calculated based on four dietary criteria: total dietary fibre, glycemic index, wholegrain/total grain carbohydrate ratio, and solid/total carbohydrate ratio. Overall and regional adiposity (total body fat, visceral fat and android-to-gynoid fat ratio) was quantified using dual-energy X-ray absorptiometry at all three time points. Multiple adjusted linear mixed-effects models were used to assess associations between concurrent changes in repeatedly measured CQI and adiposity over time., Results: After controlling for potential confounding factors, a 3-point increment in CQI over 12-month follow-up was associated with a decrease in visceral fat (β -0.067 z-score, 95% CI -0.088; -0.046, p < 0.001), android-to-gynoid fat ratio (-0.038, -0.059; -0.017, p < 0.001), and total fat (-0.064, -0.080; -0.047, p < 0.001). Fibre intake and the ratio of wholegrain/total grain showed the strongest inverse associations with all adiposity indicators., Conclusions: In this prospective cohort of older adults with overweight/obesity and MetS, we found that improvements in dietary carbohydrate quality over a year were associated with concurrent favorable changes in visceral and overall fat deposition. These associations were mostly driven by dietary fibre and the wholegrain/total grain ratio., Trial Registration: The trial was registered at the International Standard Randomized. CONTROLLED TRIAL: (ISRCTN: http://www.isrctn.com/ISRCTN89898870) with number 89898870 and registration date of 24 July 2014, retrospectively registered., Competing Interests: Conflict of interest Ramón Estruch reports receiving personal fees for educational conferences from Fundacion Cerveza y Salud, Spain, Instituto Cervantes, Alburquerque, USA; Instituto Cervantes, Milan, Italy, Instituto Cervantes, Tokyo, Japan, Fundacion Bosch i Gimpera, Spain; nonfinancial support for educational conferences from Wine and Culinary International Forum; Fees of Educational Conferences from Pernaud Richart, Mexico, Fundacion Dieta Mediterranea, Barcelona, Spain; non-financial support for travels from ERAB, Belgium, personal fees for organizing an European Conference from Brewers of Europe, Belgium; non-financial support for Organizing a Congress from Sociedad Española de Nutrición (SEN). Also feeding trials with product from Grand Fountain and Uriach Laboratories, Spain., and serving on the advisory board of Cerveza y Salud, Spain. The other authors declare no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Diets high in acid load may contribute to kidney function impairment. This study aimed to investigate the association between dietary acid load and 1-year changes in glomerular filtration rate (eGFR) and urine albumin/creatinine ratio (UACR)., Methods: Older adults with overweight/obesity and metabolic syndrome (mean age 65 ± 5 years, 48% women) from the PREDIMED-Plus study who had available data on eGFR ( n = 5,874) or UACR ( n = 3,639) at baseline and after 1 year of follow-up were included in this prospective analysis. Dietary acid load was estimated as potential renal acid load (PRAL) and net endogenous acid production (NEAP) at baseline from a food frequency questionnaire. Linear and logistic regression models were fitted to evaluate the associations between baseline tertiles of dietary acid load and kidney function outcomes. One year-changes in eGFR and UACR were set as the primary outcomes. We secondarily assessed ≥ 10% eGFR decline or ≥10% UACR increase., Results: After multiple adjustments, individuals in the highest tertile of PRAL or NEAP showed higher one-year changes in eGFR (PRAL, β: -0.64 ml/min/1.73 m 2 ; 95% CI: -1.21 to -0.08 and NEAP, β: -0.56 ml/min/1.73 m 2 ; 95% CI: -1.13 to 0.01) compared to those in the lowest category. No associations with changes in UACR were found. Participants with higher levels of PRAL and NEAP had significantly higher odds of developing ≥10% eGFR decline (PRAL, OR: 1.28; 95% CI: 1.07-1.54 and NEAP, OR: 1.24; 95% CI: 1.03-1.50) and ≥10 % UACR increase (PRAL, OR: 1.23; 95% CI: 1.04-1.46) compared to individuals with lower dietary acid load., Conclusions: Higher PRAL and NEAP were associated with worse kidney function after 1 year of follow-up as measured by eGFR and UACR markers in an older Spanish population with overweight/obesity and metabolic syndrome., Competing Interests: Author JS-S reported receiving research support from the Instituto de Salud Carlos III (ISCIII), Ministerio de Educación y Ciencia, Departament de Salut Pública de la Generalitat de Catalunya, the European Commission, the California Walnut Commission, Patrimonio Comunal Olivarero, La Morella Nuts, and Borges S.A; receiving consulting fees or travel expenses from California Walnut Commission, Eroski Foundation, Instituto Danone, Abbott Laboratories and Mundifarma, receiving non-financial support from Hojiblanca, Patrimonio Comunal Olivarero, and Almond Board of California; serving on the board of and receiving grant support through his institution from the International Nut and Dried Foundation and the Eroski Foundation; and grants and personal fees from Instituto Danone. Author ER reported receiving grants, personal fees, and non-financial support from the California Walnut Commission during the conduct of the study and grants, personal fees, non-financial support from Alexion; personal fees from Amarin; and non-financial support from the International Nut Council outside the submitted work. Author RE reported receiving grants from Instituto de Salud Carlos III and olive oil for the trial from Fundacion Patrimonio Comunal Olivarero/during the conduct of the study and personal fees from Brewers of Europe, Fundación Cerveza y Salud, Interprofesional del Aceite de Oliva, Instituto Cervantes, Pernaud Richar, Fundación Dieta Mediterránea, Wine and Culinary International Forum; non-financial support from Sociedad Española de Nutrición and Fundación Bosch y Gimpera; and grants from Uriach Laboratories outside the submitted work. Author XP reported receiving grants from ISCIII during the conduct of the study; receiving consulting fees from Sanofi Aventis, Amgen, and Abbott laboratories; receiving lecture personal fees from Esteve, Lacer and Rubio laboratories. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Valle-Hita, Becerra-Tomás, Díaz-López, Vázquez-Ruiz, Megías, Corella, Goday, Martínez, Alonso-Gómez, Wärnberg, Vioque, Romaguera, López-Miranda, Estruch, Tinahones, Lapetra, Serra-Majem, Bueno-Cavanillas, Tur, Martín-Sánchez, Pintó, Gaforio, Matía-Martín, Vidal, Amengual-Galbarte, Daimiel, Ros, García-Arellano, Barragán, Fitó, Peña-Orihuela, Asencio-Aznar, Gómez-Gracia, Martinez-Urbistondo, Morey, Casas, Garrido-Garrido, Tojal-Sierra, Damas-Fuentes, Goñi, Ortega-Azorín, Castañer, Garcia-Rios, Gisbert-Sellés, Sayón-Orea, Schröder, Salas-Salvadó and Babio.)

Purpose: To assess the association between three different a priori dietary patterns adherence (17-item energy reduced-Mediterranean Diet (MedDiet), Trichopoulou-MedDiet and Dietary Approach to Stop Hypertension (DASH)), as well as the Protein Diet Score and kidney function decline after one year of follow-up in elderly individuals with overweight/obesity and metabolic syndrome (MetS)., Methods: We prospectively analyzed 5675 participants (55-75 years) from the PREDIMED-Plus study. At baseline and at one year, we evaluated the creatinine-based estimated glomerular filtration rate (eGFR) and food-frequency questionnaires-derived dietary scores. Associations between four categories (decrease/maintenance and tertiles of increase) of each dietary pattern and changes in eGFR (ml/min/1.73m 2 ) or ≥ 10% eGFR decline were assessed by fitting multivariable linear or logistic regression models, as appropriate., Results: Participants in the highest tertile of increase in 17-item erMedDiet Score showed higher upward changes in eGFR (β: 1.87 ml/min/1.73m 2 ; 95% CI: 1.00-2.73) and had lower odds of ≥ 10% eGFR decline (OR: 0.62; 95% CI: 0.47-0.82) compared to individuals in the decrease/maintenance category, while Trichopoulou-MedDiet and DASH Scores were not associated with any renal outcomes. Those in the highest tertile of increase in Protein Diet Score had greater downward changes in eGFR (β: - 0.87 ml/min/1.73m 2 ; 95% CI: - 1.73 to - 0.01) and 32% higher odds of eGFR decline (OR: 1.32; 95% CI: 1.00-1.75)., Conclusions: Among elderly individuals with overweight/obesity and MetS, only higher upward change in the 17-item erMedDiet score adherence was associated with better kidney function after one year. However, increasing Protein Diet Score appeared to have an adverse impact on kidney health., Trial Registration Number: ISRCTN89898870 (Data of registration: 2014)., (© 2022. The Author(s).)

Background: Metabolic syndrome (MetS) worsens quality of life and increases mortality. Dissatisfaction with weight in patients with MetS may modify the effect of lifestyle interventions to achieve changes in health-related behaviors., Objective: To assess 1-year changes in cardiovascular risk scores, self-perceived general health and health-related behaviors according to observed changes in desired weight loss during the first year of intervention in a large cardiovascular prevention trial., Design: Prospective analysis of the PREDIMED-PLUS trial, including 5,499 adults (55-75 years old) with overweight or obesity at baseline., Methods: The desired weight loss was the difference between ideal and measured weight. Tertiles of change in desired weight loss (1 year vs. baseline) were defined by the following cut-off points: ≥0.0 kg (T1, n = 1,638); 0.0 to -4.0 kg (T2, n = 1,903); ≤-4.0 kg (T3, n = 1,958). A food frequency questionnaire assessed diet and the Minnesota-REGICOR questionnaire assessed physical activity. The Framingham equation assessed cardiovascular risks. The changes in the severity of MetS were also assessed. The Beck Depression Inventory assessed depressive symptoms and the SF-36 assessed health-related quality of life. Data were analyzed using general linear models., Results: BMI decreased at T2 and T3 (T1: 0.3, T2: -0.7, T3: -1.9). The most significant improvement in diet quality was observed at T3. Cardiovascular risk decreased at T2 and T3. Mean reductions in MetS severity score were: -0.02 at T1, -0.39 at T2 and -0.78 at T3. The perception of physical health increases in successive tertiles., Conclusions: In older adults with MetS, more ambitious desired weight loss goals were associated with improvements in diet, cardiovascular health and perceived physical health during the first year of a healthy lifestyle intervention programme. Weight dissatisfaction needs to be considered by health professionals., Clinical Trial Registration: http://www.isrctn.com/ISRCTN89898870, identifier 89898870., Competing Interests: Author JS-S reports serving on the board of and receiving grant support through his institution from the International Nut and Dried Fruit Council, and Eroski Foundation. Reports serving in the Executive Committee of the Instituto Danone Spain and on the Scientific Committee of the Danone International Institute. He has received research support from the Patrimonio Comunal Olivarero, Spain and Borges S.A., Spain. Reports receiving consulting fees or travel expenses from Danone; Eroski Foundation; Instituto Danone—Spain; and Abbot Laboratories. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer MM-A declared a shared affiliation with the author BR-G to the handling editor at the time of review., (Copyright © 2022 Bouzas, Bibiloni, Garcia, Mateos, Martínez-González, Salas-Salvadó, Corella, Goday, Martínez, Alonso-Gómez, Wärnberg, Vioque, Romaguera, Lopez-Miranda, Estruch, Tinahones, Lapetra, Serra-Majem, Riquelme-Gallego, Martín-Sánchez, Pintó, Gaforio, Matía, Vidal, Vázquez, Daimiel, Ros, Pascual-Roquet-Jalmar, Babio, Gonzalez-Monge, Castañer, Abete, Sorto-Sánchez, Carlos Benavente-Marín, Torres-Collado, Martin, García-Ríos, Castro-Barquero, Fernández-García, Santos-Lozano, Fernandez-Lazaro, Salas-Huetos, Guillem-Saiz, Zomeño, Ángeles Zulet, Goikoetxea-Bahon, Gea, Nishi, Schröder, Tur and the PREDIMED-Plus investigators.)

Objective: To evaluate the effect of Non-alcoholic fatty liver disease (NAFLD) status in the impact of lifestyle over Health-related quality of life (HRQoL) in patients with metabolic syndrome (MetS)., Methods: Baseline and 1 year follow up data from the PREDIMED-plus cohort (men and women, 55-75 years old with overweight/obesity and MetS) were studied. Adherence to an energy-restricted Mediterranean Diet (er-MeDiet) and Physical Activity (PA) were assessed with a validated screeners. Hepatic steatosis index (HSI) was implemented to evaluate NAFLD while the SF-36 questionnaire provided HRQoL evaluation. Statistical analyses were performed to evaluate the influence of baseline NAFLD on HRQoL as affected by lifestyle during 1 year of follow up., Results: Data from 5205 patients with mean age of 65 years and a 48% of female participants. Adjusted linear multivariate mixed regression models showed that patients with lower probability of NAFLD (HSI < 36 points) were more responsive to er-MeDiet (β 0.64 vs β 0.05 per er-MeDiet adherence point, p< 0.01) and PA (β 0.05 vs β 0.01 per MET-h/week, p = 0.001) than those with high probability for NAFLD in terms Physical SF-36 summary in the 1 year follow up. 10 points of er-MeDiet adherence and 50 MET-h/week were thresholds for a beneficial effect of lifestyle on HRQoL physical domain in patients with lower probability of NAFLD., Conclusion: The evaluation of NAFLD by the HSI index in patients with MetS might identify subjects with different prospective sensitivity to lifestyle changes in terms of physical HRQoL (http://www.isrctn.com/ISRCTN89898870)., Competing Interests: Author JS-S reports grants from CIBEROBN, ISCIII (Spain), during the conduct of the study; non-financial support from Nut and Dried Fruit Foundation, personal fees from Instituto Danone Spain, grants from Nut and Dried Fruit Foundation to this institution, grants from Eroski Distributors and personal fees from Nut and Dried Fruit Foundation, outside the submitted work. Moreover, he gratefully acknowledges the financial support by ICREA under the ICREA Academia program. The author DR declares the funding of the AstraZeneca Young Investigators Award in Category of Obesity and T2D 2017. The author RS-C acknowledges financial support from the Juan de la Cierva Program Training Grants of the Spanish State Research Agency of the Spanish Ministerio de Ciencia e Innovación y Ministerio de Universidades (FJC2018-038168- I). The author ER reports grants, personal fees, non-financial support and other from California Walnut Commission, grants, personal fees, non-financial support and other from Alexion, personal fees, non-financial support and other from Ferrer International, personal fees from Amarin, personal fees, non-financial support and other from Danone, outside the submitted work. The author JL-M reports personal fees and non-financial support from AMGEN, personal fees and non-financial support from SANOFI, personal fees from MSD, personal fees from Laboratorios Dr. Esteve, and personal fees from NOVO-NORDISK, outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Martínez-Urbistondo, San Cristóbal, Villares, Martínez-González, Babio, Corella, del Val, Ordovás, Alonso-Gómez, Wärnberg, Vioque, Romaguera, López-Miranda, Estruch, Tinahones, Lapetra, Serra-Majem, Bueno-Cavanillas, Tur, Marcos, Pintó, Delgado-Rodríguez, Matía-Martín, Vidal, Vázquez, Ros, Bullón Vela, Palau, Masagué, Abete, Moreno-Rodríguez, Candela-García, Konieczna, García-Ríos, Juárez, Martín, Goday, Zulet, Vaquero-Luna, Orea, Megías, Baltasar, Martínez and Daimiel.)

Prediabetes and not just diabetes can cause kidney damage. This study assess the association of prediabetes with development of impaired renal function (IRF). We used data from PREDAPS prospective study a cohort of 1072 subjects with prediabetes and another cohort of 772 subjects without prediabetes were follow-up from 2012 to 2017. Prediabetes was defined according to American Association of Diabetes criteria. IRF was defined as having a glomerular filtration rate < 60 mL/min/1.73 m 2 . Incidence rates of IRF in both cohorts and in different categories of prediabetes, based on impaired glycosylated hemoglobin (HbA1c) and/or fasting plasma glucose (FPG), were calculated. Hazard ratios (HR) for the association of the prediabetes with IRF, adjusting for potential confounders, were estimated by Cox regression models. Incidence rates of IRF per 100 person-years were 1.72 (95% confidence interval [CI]: 1.34-2.21) and 1.79 (95%CI: 1.45-2.20) for those without and with prediabetes, respectively .The HR of IRF in subjects with prediabetes with respect to subjects without prediabetes was 0.76 (95% CI: 0. 54-1.07). Corresponding HRs for type of prediabetes was 0.68 (95%CI: 0.40-1.15) for those with both altered parameters, 0.68 (95%CI: 00.40-1.15) for those with only impaired HbA1c and 1.12 (95%CI: 0.68-1.85) for those with only impaired FPG. The present study reflects an overall trend towards a slightly decreased risk of IRF onset associated to prediabetes except for individuals with only isolated impaired FPG. Further studies are warranted to fully assess the renal progression of each group., (© 2022. The Author(s).)

Female FMR1 (Fragile X mental retardation 1) premutation carriers are at risk for developing fragile X-associated primary ovarian insufficiency (FXPOI), a condition characterized by amenorrhea before age 40 years. Not all women with a FMR1 premutation suffer from primary ovarian insufficiency and nowadays there are no molecular or other biomarkers that can help predict the occurrence of FXPOI. Long non-coding RNAs (lncRNAs) comprise a group of regulatory transcripts which have versatile molecular functions, making them important regulators in all aspects of gene expression. In recent medical studies, lncRNAs have been described as potential diagnostic biomarkers in many diseases. The present study was designed to determine the expression profile of three lncRNAs derived from the FMR1 locus, FMR4, FMR5 and FMR6, in female FMR1 premutation carriers in order: (i) to determine a possible role in the pathogenesis of FXPOI and (ii) to investigate whether they could serve as a biomarker for the diagnosis of FXPOI. FMR4, FMR5 and FMR6 transcripts levels were evaluated in total RNA extracted from peripheral blood by digital droplet PCR and compared between FMR1 premutation carriers with FXPOI and without FXPOI. The diagnostic value of lncRNAs was evaluated by receiver operating characteristic (ROC) analysis. Results revealed a significant association between FXPOI and high expression levels of FMR4. No association was obtained for FMR5 or FMR6. ROC curve analysis revealed that FMR4 can distinguish FMR1 premutation carrier with FXPOI with a diagnostic power of 0.67. These findings suggest a potential role of FMR4 as a possible biomarker for FXPOI.

Purpose: Long-term nutrition trials may fail to respond to their original hypotheses if participants do not comply with the intended dietary intervention. We aimed to identify baseline factors associated with successful dietary changes towards an energy-reduced Mediterranean diet (MedDiet) in the PREDIMED-Plus randomized trial., Methods: Longitudinal analysis of 2985 participants (Spanish overweight/obese older adults with metabolic syndrome) randomized to the active intervention arm of the PREDIMED-Plus trial. Dietary changes were assessed with a 17-item energy-reduced MedDiet questionnaire after 6 and 12 months of follow-up. Successful compliance was defined as dietary changes from baseline of ≥ 5 points for participants with baseline scores < 13 points or any increase if baseline score was ≥ 13 points. We conducted crude and adjusted multivariable logistic regression models to identify baseline factors related to compliance., Results: Consistent factors independently associated with successful dietary change at both 6 and 12 months were high baseline perceived self-efficacy in modifying diet (OR 6-month : 1.51, 95% CI 1.25-1.83; OR 12-month : 1.66, 95% CI 1.37-2.01), higher baseline fiber intake (OR 6-month : 1.62, 95% CI 1.07-2.46; OR 12-month : 1.62, 95% CI 1.07-2.45), having > 3 chronic conditions (OR 6-month : 0.65, 95% CI 0.53-0.79; OR 12-month : 0.76, 95% CI 0.62-0.93), and suffering depression (OR 6-month : 0.80, 95% CI 0.64-0.99; OR 12-month : 0.71, 95% CI 0.57-0.88)., Conclusion: Our results suggested that recruitment of individuals with high perceived self-efficacy to dietary change, and those who initially follow diets relatively richer in fiber may lead to greater changes in nutritional recommendations. Participants with multiple chronic conditions, specifically depression, should receive specific tailored interventions., Trial Registration: ISRCTN registry 89898870, 24th July 2014 retrospectively registered http://www.isrctn.com/ISRCTN89898870 ., (© 2021. The Author(s).)

Purpose: Inflammation could play a key role in tissue damage and bone metabolism. The modified dietary inflammatory score (M-DIS) is a validated tool to estimate the inflammatory potential of the diet. In the present study, we evaluate the associations between the M-DIS and bone mineral density (BMD) in a senior Mediterranean population with overweight/obesity and metabolic syndrome., Methods: Baseline cross-sectional association between the M-DIS and bone mineral density was assessed in 1134 participants of the multicenter PREDIMED-Plus trial (aged 55-75 with overweight/obesity and metabolic syndrome). BMD was measured using Dual-energy X-ray Absorptiometry scans and participants answered a food frequency questionnaire to determine the M-DIS. BMD was categorized as low BMD when T score was equal or lower than -1 and normal BMD in another case. Associations between BMD and M-DIS were evaluated by using linear and logistic regressions adjusted by other co-variates., Results: Participants in the top tertile of the M-DIS had a lower BMD at total femur [β (95% CI) - 0.02 (- 0.04, - 0.01)], trochanter areas [β (95% CI) - 0.03 (- 0.05, - 0.01)] and lumbar spine area [β (95% CI) - 0.03 (- 0.07, 0.01)] (but in the last case, measures were less precise and hence not statistically significant) compared to those in the lower M-DIS tertile. Multiple logistic regression analyses showed that the odds of the total femur and femoral trochanter osteopenia/osteoporosis were higher in participants in the top tertile compared to those in the lowest tertile of M-DIS [OR (95% CI) 1.71 (1.12, 2.64), P for trend 0.015; 2.02 (1.29, 3.21), P for trend 0.002, respectively]., Conclusion: A high pro-inflammatory diet, measured by the M-DIS, is associated with lower BMD in a senior Mediterranean population with metabolic syndrome., (© 2021. The Author(s).)

Obesity-related hyperfiltration leads to an increased glomerular filtration rate (GFR) and hyperalbuminuria. These changes are reversible after bariatric surgery (BS). We aimed to explore obesity-related renal changes post-BS and to seek potential mechanisms. Sixty-two individuals with severe obesity were prospectively examined before and 3, 6 and 12 months post-BS. Anthropometric and laboratory data, 24 h-blood pressure, renin-angiotensin-aldosterone system (RAS) components, adipokines and inflammatory markers were determined. Both estimated GFR (eGFR) and albuminuria decreased from the baseline at all follow-up times ( p -for-trend <0.001 for both). There was a median (IQR) of 30.5% (26.2-34.4) reduction in body weight. Plasma glucose, glycosylated hemoglobin, fasting insulin and HOMA-index decreased at 3, 6 and 12 months of follow-up ( p -for-trend <0.001 for all). The plasma aldosterone concentration (median (IQR)) also decreased at 12 months (from 87.8 ng/dL (56.8; 154) to 65.4 (56.8; 84.6), p = 0.003). Both leptin and hs-CRP decreased ( p < 0.001) and adiponectine levels increased at 12 months post-BS ( p = 0.017). Linear mixed-models showed that body weight (coef. 0.62, 95% CI: 0.32 to 0.93, p < 0.001) and plasma aldosterone (coef. -0.07, 95% CI: -0.13 to -0.02, p = 0.005) were the independent variables for changes in eGFR. Conversely, glycosylated hemoglobin was the only independent variable for changes in albuminuria (coef. 0.24, 95% CI: 0.06 to 0.42, p = 0.009). In conclusion, body weight and aldosterone are the main factors that mediate eGFR changes in obesity and BS, while albuminuria is associated with glucose homeostasis.

Background: No studies have evaluated the effect of metabolic and bariatric surgery (MBS) on nonalcoholic fatty liver disease (NAFLD) and cardiometabolic markers in metabolically healthy patients with morbid obesity (MHMO) at midterm., Objectives: To assess the effect of MBS on NAFLD and cardiometabolic markers in MHMO patients and ascertain whether metabolically unhealthy patients with morbid obesity (MUMO) remain metabolically healthy at 5 years after MBS., Setting: University hospital., Methods: A total of 191 patients with a body mass index >40 kg/m 2 and at least 5 years of follow-up were retrospectively analyzed. Lost to follow-up were 37.6% (151 of 401 patients). Patients were classified as MHMO if 1 or 0 of the cardiometabolic markers were present using the Wildman criteria. The degree of liver fibrosis was assessed using the NAFLD fibrosis score (NFS)., Results: Forty-one patients (21.5%) fulfilled the criteria for MHMO. They showed significant improvements in blood pressure (from 135.1 ± 22.1 and 84.2 ± 14.3 mm Hg to 117.7 ± 19.2 and 73.0 ± 10.9 mm Hg), plasma glucose (from 91.0 ± 5.6 mg/dL to 87.2 ± 5.2 mg/dL), homeostatic model assessment for insulin resistance (from 2.2 ± .9 to 1.0 ± .8), triglycerides (from 88.0 [range, 79.5-103.5] mg/dL to 61.0 [range, 2.0-76.5] mg/dL), alanine aminotransferase, gamma-glutamyl transpeptidase NFS (from -1.0 ± 1.0 to -1.9 ± 1.2), and high-density lipoprotein cholesterol (from 56.9 ± 10.5 mg/dL to 77.9 ± 17.4 mg/dL) at 5 years after surgery. A total of 108 MUMO patients (84.4%) who became metabolically healthy after 1 year stayed healthy at 5 years., Conclusions: MBS induced a midterm improvement in cardiometabolic and NAFLD markers in MHMO patients. Seventy-six percent of MUMO patients became metabolically healthy at 5 years after MBS., (Copyright © 2021 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Introduction: Type 2 diabetes has been linked to greater cognitive decline, but other glycemic parameters such as prediabetes, diabetes control and treatment, and HOMA-IR and HbA 1c diabetes-related biomarkers have shown inconsistent results. Furthermore, there is limited research assessing these relationships in short-term studies. Thus, we aimed to examine 2-year associations between baseline diabetes/glycemic status and changes in cognitive function in older participants at high risk of cardiovascular disease., Methods: We conducted a 2-year prospective cohort study (n=6,874) within the framework of the PREDIMED-Plus study. The participants (with overweight/obesity and metabolic syndrome; mean age 64.9 years; 48.5% women) completed a battery of 8 cognitive tests, and a global cognitive function Z-score (GCF) was estimated. At baseline, participants were categorized by diabetes status (no-diabetes, prediabetes, and <5 or ≥5-year diabetes duration), and also by diabetes control. Furthermore, insulin resistance (HOMA-IR) and glycated hemoglobin (HbA 1c ) levels were measured, and antidiabetic medications were recorded. Linear and logistic regression models, adjusted by potential confounders, were fitted to assess associations between glycemic status and changes in cognitive function., Results: Prediabetes status was unrelated to cognitive decline. However, compared to participants without diabetes, those with ≥5-year diabetes duration had greater reductions in GCF (β=-0.11 (95%CI -0.16;-0.06)], as well as in processing speed and executive function measurements. Inverse associations were observed between baseline HOMA-IR and changes in GCF [β=-0.0094 (95%CI -0.0164;-0.0023)], but also between HbA 1c levels and changes in GCF [β=-0.0085 (95%CI -0.0115, -0.0055)], the Mini-Mental State Examination, and other executive function tests. Poor diabetes control was inversely associated with phonologic fluency. The use of insulin treatment was inversely related to cognitive function as measured by the GCF [β=-0.31 (95%CI -0.44, -0.18)], and other cognitive tests., Conclusions: Insulin resistance, diabetes status, longer diabetes duration, poor glycemic control, and insulin treatment were associated with worsening cognitive function changes in the short term in a population at high cardiovascular risk., Clinical Trial Registration: http://www.isrctn.com/ISRCTN89898870, identifier ISRCTN: 89898870., Competing Interests: JS-S serves on the board of the International Nut and Dried Fruit Council and receives grant support through this institution. He also served on the Executive Committee of the Instituto Danone, Spain, and on the Scientific Committee of the Danone International Institute. He has received research support from the Patrimonio Comunal Olivarero, Spain, and Borges S.A., Spain. He receives consulting fees or travel expenses from Eroski Foundation, the Instituto Danone, Spain, Mundipharma and Abbot Laboratories. ER reports grants, personal fees, non-financial support and others from California Walnut Commission and Alexion, personal fees, non-financial support and others from Ferrer International and Danone, and personal fees from Amarin, outside the submitted work. FF-A reports consultation fees from Novo Nordisk and editor-in-Chief honoraria from Wiley. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gómez-Martínez, Babio, Júlvez, Becerra-Tomás, Martínez-González, Corella, Castañer, Romaguera, Vioque, Alonso-Gómez, Wärnberg, Martínez, Serra-Majem, Estruch, Tinahones, Lapetra, Pintó, Tur, López-Miranda, Bueno-Cavanillas, Gaforio, Matía-Martín, Daimiel, Martín-Sánchez, Vidal, Vázquez, Ros, Dalsgaard, Sayón-Orea, Sorlí, de la Torre, Abete, Tojal-Sierra, Barón-López, Fernández-Brufal, Konieczna, García-Ríos, Sacanella, Bernal-López, Santos-Lozano, Razquin, Alvarez-Sala, Goday, Zulet, Vaquero-Luna, Diez-Espino, Cuenca-Royo, Fernández-Aranda, Bulló and Salas-Salvadó.)

This baseline cross-sectional analysis from data acquired in a sub-sample of the PREDIMED-Plus study participants aimed to evaluate the relation between the Composite Socioeconomic Index (CSI) and lifestyle (diet and physical activity). This study involved 1512 participants (759 (52.2%) women) between 55 and 80 years with overweight/obesity and metabolic syndrome assigned to 137 primary healthcare centers in Catalonia, Spain. CSI and lifestyle (diet and physical activity) were assessed. Multiple linear regression or multinomial regression were applied to the data. Cluster analysis was performed to identify dietary patterns. The multiple linear regression model showed that a high deprivation index was related to a higher consumption of refined cereals (11.98 g/d, p -value = 0.001) and potatoes (6.68 g/d, p -value = 0.001), and to a lower consumption of fruits (-17.52 g/d, p -value = 0.036), and coffee and tea (-8.03 g/d, p -value = 0.013). Two a posteriori dietary patterns were identified by cluster analysis and labeled as "healthy" and "unhealthy". In addition, the multinomial regression model showed that a high deprivation index was related to an unhealthy dietary pattern and low physical activity (OR 1.42 [95% CI 1.06-1.89]; p -value < 0.05). In conclusion, a high deprivation index was related to an unhealthy lifestyle (diet and physical activity) in PREDIMED-Plus study participants.

Background and Aims: Modifiable lifestyle factors, such as physical activity (PA) and Mediterranean diet (MD), decrease metabolic syndrome (MetS). The aim was to assess 1-year changes of leisure-time physical activity (LTPA), sedentary behavior, and diet quality according to MetS severity in older population at high cardiovascular risk., Methods and Results: Prospective analysis of 55-75-year-old 4359 overweight/obese participants with MetS (PREDIMED-Plus trial) categorized in tertiles according to 1-year changes of a validated MetS severity score (MetSSS). Anthropometrics, visceral adiposity index, triglycerides and glucose index, dietary nutrient intake, biochemical marker levels, dietary inflammatory index, and depression symptoms were measured. Diet quality was assessed by 17-item MD questionnaire. PAs were self-reported using the Minnesota-REGICOR Short Physical Activity Questionnaire and 30-s chair stand test. Sedentary behaviors were measured using the Spanish version of the Nurses' Health Study questionnaire. After 1-year follow-up, decreasing MetSSS was associated with an anti-inflammatory dietary pattern, high intake of vegetables, fruits, legumes, nuts, whole grain cereals, white fish, and bluefish and low intake of refined cereals, red and processed meat, cookies/sweets, and snacks/ready-to-eat-meals. It resulted in high intake of polyunsaturated fatty acids, omega-3 fatty acids, protein, fiber, vitamins B1, B6, B9, C, D, potassium, magnesium, and phosphorus and low glycemic index and saturated fatty acid, trans fatty acid, and carbohydrates intake. Regarding PA and sedentary behavior, decreasing MetSSS was associated with increased moderate-to-vigorous LTPA, chair stand test, and decreased sedentary and TV-viewing time., Conclusion: Decreasing MetSSS was associated with an anti-inflammatory dietary pattern, high LTPA, high MD adherence, low sedentary time, and low depression risk., Competing Interests: Declaration of competing interest J.S.-S. reports serving on the board of and receiving grant support through his institution from the International Nut and Dried Fruit Council, and Eroski Foundation. Reports serving in the Executive Committee of the Instituto Danone Spain and on the Scientific Committee of the Danone International Institute. He has received research support from Patrimonio Comunal Olivarero, Spain; and Borges SA, Spain. Reports receiving consulting fees or travel expenses from Danone; Eroski Foundation, Instituto Danone—Spain, and Abbot Laboratories., (Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

A clear pathogenetic association exists between obesity and arterial hypertension, becoming even more evident in subjects with severe obesity. Bariatric surgery has proved to be the most effective treatment for severe obesity, with its benefits going beyond weight loss. The present review aimed to determine the effects of bariatric surgery on arterial hypertension evident in short- and long-term follow-ups. Moreover, the differences between surgical techniques regarding hypertension remission are described as well as the possible pathophysiologic mechanisms involved. In addition, the effects of bariatric surgery beyond blood pressure normalization are also analyzed, including those on target organs and cardiovascular morbidity and mortality.

Objective: Information about prognostic outcomes can be of great help for people with prediabetes and for physicians in the face of scientific controversy about the cutoff point for defining prediabetes. We aimed to estimate different prognostic outcomes in people with prediabetes., Design: Prospective cohort of subjects with prediabetes according to American Diabetes Association guidelines., Main Outcome Measures: The probabilities of diabetes onset versus non-onset, the odds against diabetes onset, and the probability of reverting to normoglycemia according to different prediabetes categories were calculated., Results: The odds against diabetes onset ranged from 29:1 in individuals with isolated FPG of 100-109 mg/dL to 1:1 in individuals with FPG 110-125 mg/dL plus HbA1c 6.0-6.4%. The probability of reversion to normoglycemia was 31.2% (95% CI 24.0-39.6) in those with isolated FPG 100-109 mg/dL and 6.2% (95% CI 1.4-10.0) in those with FPG 110-125 mg/dL plus HbA1c 6.0-6.4%. Of every 100 participants in the first group, 97 did not develop diabetes and 31 reverted to normoglycemia, while in the second group those figures were 52 and 6., Conclusions: Using odds of probabilities and absolute numbers might be useful for people with prediabetes and physicians to share decisions on potential interventions.Key pointsCommunicating knowledge on the course of the disease to make clinical decisions is not always done appropriately.Prediabetes is an example where risk communication is important because the prognosis of subjects with prediabetes is very heterogeneous.Depending on fasting plasma glucose and HbA1c levels, the odds of probabilities against diabetes onset ranged from 29: 1 to 1: 1.Depending on fasting plasma glucose and HbA1c levels, the number of subjects in 100 who revert to normoglycemia ranged from 31 to 6.Using probabilities and number absolutes on the prognosis of prediabetes may be useful for people with prediabetes and physicians to share decisions on potential interventions.

Our aim was to evaluate whether fatty liver index (FLI) is associated with the risk of type 2 diabetes (T2DM) development within the Spanish adult population and according to their prediabetes status; additionally, to examine its incremental predictive value regarding traditional risk factors. A total of 2260 subjects (Prediabetes: 641 subjects, normoglycemia: 1619 subjects) from the Di@bet.es cohort study were studied. Socio-demographic, anthropometric, clinical data and survey on habits were recorded. An oral glucose tolerance test was performed and fasting determinations of glucose, lipids and insulin were made. FLI was calculated and classified into three categories: Low (< 30), intermediate (30-60) and high (> 60). In total, 143 people developed diabetes at follow-up. The presence of a high FLI category was in all cases a significant independent risk factor for the development of diabetes. The inclusion of FLI categories in prediction models based on different conventional T2DM risk factors significantly increase the prediction power of the models when all the population was considered. According to our results, FLI might be considered an early indicator of T2DM development even under normoglycemic condition. The data also suggest that FLI could provide additional information for the prediction of T2DM in models based on conventional risk factors., (© 2021. The Author(s).)

Research Question: What are the hormonal and ovarian histological effects of a gender affirming hormonal therapy in assigned female at birth (AFAB) transgender people?, Design: Prospective observational study of 70 AFAB transgender people taking testosterone therapy before gender-affirming surgery (hystero-oophorectomy). A gynaecological ultrasonographic scan was undertaken and serum hormone concentrations measured, including anti-Müllerian hormone (AMH) and androgenic profile. Histological ovarian evaluation was assessed in both ovaries, including the developmental stages of the follicles., Results: The mean age of the population was 27.7+/-5.14 years. The main biochemical parameters were total testosterone levels 781.5 ± 325.9 ng/dl; AMH levels 3.2 ± 1.4 ng/ml; FSH and LH levels 4.9 ± 2.5 IU/l and 3.9 ± 2.9 IU/l, respectively; and oestradiol values 47.6 ± 13.7 pg/ml. Fifty-five AFAB underwent gynaecological ultrasound before surgery and antral follicles were found in 43 out of 47 ultrasounds (91.5%) (without the presence of a dominant follicle or corpus luteum). Histological follicles were mostly in the primordial stage (88.0) and 3.3% were atretic. The thickness of the tunica albuginea was widely heterogeneous (range 0.15-1.45 mm) and luteinization of the stromal cells was observed in 68.6% of the samples. A negative correlation between testosterone levels and total antral follicles was found (R s = -0.306, P = 0.029)., Conclusions: AFAB transgender people taking testosterone therapy show cortical follicle distribution in the range previously reported in fertile cisgender women of reproductive age. The follicular population may not be altered as a result of the gender-affirming hormonal therapy, although some cortical and stromal changes have been observed., (Copyright © 2021 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)