Impact of nocturnal hypoxia on glycaemic control, appetite, gut microbiota and inflammation in adults with type 2 diabetes mellitus: A single-blind cross-over trial.

High altitude residents have a lower incidence of type 2 diabetes mellitus (T2DM). Therefore, we examined the effect of repeated overnight normobaric hypoxic exposure on glycaemic control, appetite, gut microbiota and inflammation in adults with T2DM. Thirteen adults with T2DM [glycated haemoglobin (HbA1c): 61.1 ± 14.1 mmol mol-1; aged 64.2 ± 9.4 years; four female] completed a single-blind, randomised, sham-controlled, cross-over study for 10 nights, sleeping when exposed to hypoxia (fractional inspired O2 [ F I O 2 ${{F}_{{\mathrm{I}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$ ] = 0.155; ∼2500 m simulated altitude) or normoxic conditions ( F I O 2 ${{F}_{{\mathrm{I}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$  = 0.209) in a randomised order. Outcome measures included: fasted plasma [glucose]; [hypoxia inducible factor-1α]; [interleukin-6]; [tumour necrosis factor-α]; [interleukin-10]; [heat shock protein 70]; [butyric acid]; peak plasma [glucose] and insulin sensitivity following a 2 h oral glucose tolerance test; body composition; appetite indices ([leptin], [acyl ghrelin], [peptide YY], [glucagon-like peptide-1]); and gut microbiota diversity and abundance [16S rRNA amplicon sequencing]. During intervention periods, accelerometers measured physical activity, sleep duration and efficiency, whereas continuous glucose monitors were used to assess estimated HbA1c and glucose management indicator and time in target range. Overnight hypoxia was not associated with changes in any outcome measure (P > 0.05 with small effect sizes) except fasting insulin sensitivity and gut microbiota alpha diversity, which exhibited trends (P = 0.10; P = 0.08 respectively) for a medium beneficial effect (d = 0.49; d = 0.59 respectively). Ten nights of overnight moderate hypoxic exposure did not significantly affect glycaemic control, gut microbiome, appetite, or inflammation in adults with T2DM. However, the intervention was well tolerated and a medium effect-size for improved insulin sensitivity and reduced alpha diversity warrants further investigation. KEY POINTS: Living at altitude lowers the incidence of type 2 diabetes mellitus (T2DM). Animal studies suggest that exposure to hypoxia may lead to weight loss and suppressed appetite. In a single-blind, randomised sham-controlled, cross-over trial, we assessed the effects of 10 nights of hypoxia (fractional inspired O2 ∼0.155) on glucose homeostasis, appetite, gut microbiota, inflammatory stress ([interleukin-6]; [tumour necrosis factor-α]; [interleukin-10]) and hypoxic stress ([hypoxia inducible factor 1α]; heat shock protein 70]) in 13 adults with T2DM. Appetite and inflammatory markers were unchanged following hypoxic exposure, but an increased insulin sensitivity and reduced gut microbiota alpha diversity were associated with a medium effect-size and statistical trends, which warrant further investigation using a definitive large randomised controlled trial. Hypoxic exposure may represent a viable therapeutic intervention in people with T2DM and particularly those unable or unwilling to exercise because barriers to uptake and adherence may be lower than for other lifestyle interventions (e.g. diet and exercise).

UPDATE trial: investigating the effects of ultra-processed versus minimally processed diets following UK dietary guidance on health outcomes: a protocol for an 8-week community-based cross-over randomised controlled trial in people with overweight or obesity, followed by a 6-month behavioural intervention.

INTRODUCTION: Obesity increases the risk of morbidity and mortality. A major driver has been the increased availability of ultra-processed food (UPF), now the main UK dietary energy source. The UK Eatwell Guide (EWG) provides public guidance for a healthy balanced diet but offers no UPF guidance. Whether a healthy diet can largely consist of UPFs is unclear. No study has assessed whether the health impact of adhering to dietary guidelines depends on food processing. Furthermore, our study will assess the impact of a 6-month behavioural support programme aimed at reducing UPF intake in people with overweight/obesity and high UPF intakes. METHODS AND ANALYSIS: UPDATE is a 2×2 cross-over randomised controlled trial with a 6-month behavioural intervention. Fifty-five adults aged ≥18, with overweight/obesity (≥25 to <40 kg/m2), and ≥50% of habitual energy intake from UPFs will receive an 8-week UPF diet and an 8-week minimally processed food (MPF) diet delivered to their home, both following EWG recommendations, in a random order, with a 4-week washout period. All food/drink will be provided. Participants will then receive 6 months of behavioural support to reduce UPF intake. The primary outcome is the difference in weight change between UPF and MPF diets from baseline to week 8. Secondary outcomes include changes in diet, waist circumference, body composition, heart rate, blood pressure, cardiometabolic risk factors, appetite regulation, sleep quality, physical activity levels, physical function/strength, well-being and aspects of behaviour change/eating behaviour at 8 weeks between UPF/MPF diets, and at 6-month follow-up. Quantitative assessment of changes in brain MRI functional resting-state connectivity between UPF/MPF diets, and qualitative analysis of the behavioural intervention for feasibility and acceptability will be undertaken. ETHICS AND DISSEMINATION: Sheffield Research Ethics Committee approved the trial (22/YH/0281). Peer-reviewed journals, conferences, PhD thesis and lay media will report results. TRIAL REGISTRATION NUMBER: NCT05627570.

Weight-loss Independent Clinical and Metabolic Biomarkers Associated with Type 2 Diabetes Remission Post-bariatric/metabolic Surgery.

PURPOSE: Remission of type 2 diabetes (T2D) can be achieved by many, but not all, people following bariatric/metabolic surgery. The mechanisms underlying T2D remission remain incompletely understood. This observational study aimed to identify novel weight-loss independent clinical, metabolic and genetic factors that associate with T2D remission using comprehensive phenotyping. MATERIALS AND METHODS: Ten patients without T2D remission (non-remitters) were matched to 10 patients with T2D remission (remitters) for age, sex, type of surgery, body weight, BMI, post-operative weight loss, duration from surgery and duration of T2D. Detailed body composition assessed using magnetic resonance imaging, gut hormones, serum metabolomics, insulin sensitivity, and genetic risk scores for T2D and anthropometric traits were assessed. RESULTS: Remitters had significantly greater ß-cell function and circulating acyl ghrelin levels, but lower visceral adipose tissue (VAT): subcutaneous adipose tissue (SAT) ratio than non-remitters. Branched-chain amino acids (BCAAs) and VLDL particle size were the most discriminant metabolites between groups. A significant positive correlation between, VAT area, VAT:SAT ratio and circulating levels of BCAAs was observed, whereas a significant negative correlation between BCAAs and ß-cell function was revealed. CONCLUSION: We highlight a potentially novel relationship between VAT and BCAAs, which may play a role in glucoregulatory control. Improvement in ß-cell function, and the role ghrelin plays in its recovery, is likely another key factor influencing T2D remission post-surgery. These findings suggest that adjunctive approaches that target VAT loss and restoration of BCAA metabolism might achieve higher rates of long-term T2D remission post-surgery.

Metabolic and Bariatric Endoscopy: A Mini-Review.

We are currently in a worldwide obesity pandemic, which is one of the most significant health problems of the 21st century. As the prevalence of obesity continues to rise, new and innovate treatments are becoming available. Metabolic and bariatric endoscopic procedures are exciting new areas of gastroenterology that have been developed as a direct response to the obesity crisis. These novel interventions offer a potentially reversible, less invasive, safer, and more cost-effective method of tackling obesity compared to traditional bariatric surgery. Minimally invasive endoscopic treatments are not entirely novel, but as technology has rapidly improved, many of the procedures have been proven to be extremely effective for weight loss and metabolic health, based on high-quality clinical trial data. This mini-review examines the existing evidence for the most prominent metabolic and bariatric procedures, followed by a discussion on the future trajectory of this emerging subspecialty.

Safety and Efficacy of Liraglutide, 3.0 mg, Once Daily vs Placebo in Patients With Poor Weight Loss Following Metabolic Surgery: The BARI-OPTIMISE Randomized Clinical Trial.

Importance: Metabolic surgery leads to weight loss and improved health, but these outcomes are highly variable. Poor weight loss is associated with lower circulating levels of glucagon-like peptide-1 (GLP-1). Objective: To assess the efficacy and safety of the GLP-1 receptor agonist, liraglutide, 3.0 mg, on percentage body weight reduction in patients with poor weight loss and suboptimal GLP-1 response after metabolic surgery. Design, Setting, and Participants: The Evaluation of Liraglutide 3.0 mg in Patients With Poor Weight Loss and a Suboptimal Glucagon-Like Peptide-1 Response (BARI-OPTIMISE) randomized placebo-controlled trial recruited adult patients at least 1 year after metabolic surgery who had experienced 20% or less body weight loss from the day of surgery and a suboptimal nutrient-stimulated GLP-1 response from 2 hospitals in London, United Kingdom, between October 2018 and November 2019. Key exclusion criteria were type 1 diabetes; severe concomitant psychiatric, gastrointestinal, cardiac, kidney or metabolic disease; and use of insulin, GLP-1 receptor analogues, and medication that can affect weight. The study period was 24 weeks followed by a 4-week follow-up period. Last participant follow-up was completed in June 2020. All participants and clinical study personnel were blinded to treatment allocation. Of 154 assessed for eligibility, 70 met trial criteria and were included in the study, and 57 completed follow-up. Interventions: Liraglutide, 3.0 mg, once daily or placebo as an adjunct to lifestyle intervention with a 500-kcal daily energy deficit for 24 weeks, on a 1:1 allocation by computer-generated randomization sequence, stratified by surgery type (Roux-en-Y gastric bypass [RYGB] or sleeve gastrectomy [SG]) and type 2 diabetes status. Main Outcome and Measures: The primary outcome was change in percentage body weight from baseline to the end of the 24-week study period based on an intention-to-treat analysis. Participant safety was assessed through monitoring of biochemical parameters, including kidney and liver function, physical examination, and assessment for adverse events. Results: A total of 70 participants (mean [SD] age, 47.6 [10.7] years; 52 [74%] female) with a poor weight loss response following RYGB or SG were randomized to receive 3.0-mg liraglutide (n = 35) or placebo (n = 35). All participants received at least 1 dose of the trial drug. Eight participants discontinued treatment (4 per group), and 2 in the 3.0-mg liraglutide group and 1 in the placebo group were lost to follow-up. Due to COVID-19 restrictions, 3 participants in the 3.0-mg liraglutide group and 7 in the placebo group were unable to attend their final in-person assessment. Estimated change in mean (SD) percentage body weight from baseline to week 24 was -8.82 (4.94) with liraglutide, 3.0 mg (n = 31), vs -0.54 (3.32) with placebo (n = 26). The mean difference in percentage body weight change for liraglutide, 3.0 mg, vs placebo was -8.03 (95% CI, -10.39 to -5.66; P < .001). Adverse events, predominantly gastrointestinal, were more frequent with liraglutide, 3.0 mg (28 events [80%]), than placebo (20 events [57%]). There were no serious adverse events and no treatment-related deaths. Conclusion and Relevance: These findings support the use of adjuvant liraglutide, 3.0 mg, for weight management in patients with poor weight loss and suboptimal GLP-1 response after metabolic surgery. Trial Registration: ClinicalTrials.gov Identifier: NCT03341429.

Aberrant olfactory network functional connectivity in people with olfactory dysfunction following COVID-19 infection: an exploratory, observational study.

Background: Olfactory impairments and anosmia from COVID-19 infection typically resolve within 2-4 weeks, although in some cases, symptoms persist longer. COVID-19-related anosmia is associated with olfactory bulb atrophy, however, the impact on cortical structures is relatively unknown, particularly in those with long-term symptoms. Methods: In this exploratory, observational study, we studied individuals who experienced COVID-19-related anosmia, with or without recovered sense of smell, and compared against individuals with no prior COVID-19 infection (confirmed by antibody testing, all vaccine naïve). MRI Imaging was carried out between the 15th July and 17th November 2020 at the Queen Square House Clinical Scanning Facility, UCL, United Kingdom. Using functional magnetic resonance imaging (fMRI) and structural imaging, we assessed differences in functional connectivity (FC) between olfactory regions, whole brain grey matter (GM) cerebral blood flow (CBF) and GM density. Findings: Individuals with anosmia showed increased FC between the left orbitofrontal cortex (OFC), visual association cortex and cerebellum and FC reductions between the right OFC and dorsal anterior cingulate cortex compared to those with no prior COVID-19 infection (p < 0.05, from whole brain statistical parametric map analysis). Individuals with anosmia also showed greater CBF in the left insula, hippocampus and ventral posterior cingulate when compared to those with resolved anosmia (p < 0.05, from whole brain statistical parametric map analysis). Interpretation: This work describes, for the first time to our knowledge, functional differences within olfactory areas and regions involved in sensory processing and cognitive functioning. This work identifies key areas for further research and potential target sites for therapeutic strategies. Funding: This study was funded by the National Institute for Health and Care Research and supported by the Queen Square Scanner business case.

Impact of sleeve gastrectomy compared to Roux-en-y gastric bypass upon hedonic hunger and the relationship to post-operative weight loss.

'Hedonic hunger' indicates the desire to consume food in the absence of an energy requirement. Hedonic hunger can be investigated using the validated Power of Food Scale (PFS). Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are currently the most effective treatment options for severe obesity. Following RYGB, hedonic hunger diminishes, which may contribute to sustained weight loss. There are no data examining the effect of SG on hedonic hunger. We prospectively evaluated hedonic hunger using PFS in patients with severe obesity prior to and 6 months after SG (n = 95) or RYGB (n = 44) and investigated the procedure-specific relationship between percentage weight loss (%WL) and hedonic hunger. Anthropometric data were collected at baseline after 6 months, 12 months and 24 months post-operatively. PFS contains 15 items grouped into 3 domains considering when food is: available (FA), present (FP), tasted (FT) and a total score (TS). At 6 months, a significant reduction was seen in all categories post-SG (p < 0.0001) and in TS (p = 0.003), FA (p = 0.0006) and FP (p = 0.0007) post-RYGB. A significantly larger reduction in FP scores was seen post-SG (p = 0.01). Post-SG, a significant correlation with 6-month %WL was noted for changes in FP (p = 0.03) and TS (p = 0.03). Post-SG changes in FP and TS predicted 24-month %WL. Post-RYGB significant correlations were seen between 6-month %WL and dFA (p = 0.04) and dFP (p = 0.03). Changes in FA, FP and TS were predictive of 12-month %WL. HH is reduced following both SG and RYGB with a greater reduction following SG and is related to post-operative %WL. PFS may have a role as a predictive tool for post-operative outcomes following SG and RYGB.

Distorted chemosensory perception and female sex associate with persistent smell and/or taste loss in people with SARS-CoV-2 antibodies: a community based cohort study investigating clinical course and resolution of acute smell and/or taste loss in people with and without SARS-CoV-2 antibodies in London, UK.

BACKGROUND: Loss of smell and/or taste are cardinal symptoms of COVID-19. 'Long-COVID', persistence of symptoms, affects around one fifth of people. However, data regarding the clinical resolution of loss of smell and/or taste are lacking. In this study we assess smell and taste loss resolution at 4-6 week follow-up, aim to identify risk factors for persistent smell loss and describe smell loss as a feature of long-COVID in a community cohort in London with known SARS-CoV-2 IgG/IgM antibody status. We also compare subjective and objective smell assessments in a subset of participants. METHODS: Four hundred sixty-seven participants with acute loss of smell and/or taste who had undergone SARS-CoV-2 IgG/IgM antibody testing 4-6 weeks earlier completed a follow-up questionnaire about resolution of their symptoms. A subsample of 50 participants completed an objective olfactory test and results were compared to subjective smell evaluations. RESULTS: People with SARS-CoV-2 antibodies with an acute loss of sense of smell and taste were significantly less likely to recover their sense of smell/taste than people who were seronegative (smell recovery: 57.7% vs. 72.1%, p = 0.027. taste recovery 66.2% vs. 80.3%, p = 0.017). In SARS-CoV-2 positive participants, a higher percentage of male participants reported full resolution of smell loss (72.8% vs. 51.4%; p < 0.001) compared to female participants, who were almost 2.5-times more likely to have ongoing smell loss after 4-6 weeks (OR 2.46, 95%CI 1.47-4.13, p = 0.001). Female participants with SARS-CoV-2 antibodies and unresolved smell loss and unresolved taste loss were significantly older (> 40 years) than those who reported full resolution. Participants who experienced parosmia reported lower smell recovery rates and participants with distorted taste perception lower taste recovery rates. Parosmia had a significant association to unresolved smell loss (OR 2.47, 95%CI 1.54-4.00, p < 0.001). CONCLUSION: Although smell and/or taste loss are often transient manifestations of COVID-19, 42% of participants had ongoing loss of smell, 34% loss of taste and 36% loss of smell and taste at 4-6 weeks follow-up, which constitute symptoms of 'long-COVID'. Females (particularly > 40 years) and people with a distorted perception of their sense of smell/taste are likely to benefit from prioritised early therapeutic interventions. TRIALS REGISTRATION: ClinicalTrials.gov NCT04377815 Date of registration: 23/04/2020.

Mechanisms of weight regain.

Weight regain following weight loss is frequent problem that people with obesity face. This weight recidivism is often attributed to the lack of compliance with appropriate food habits and exercise. On the contrary, it is known that body weight and fat mass are regulated by numerous physiological mechanisms, far beyond voluntary food intake and physical exercise. Thus, the aim of this paper is to review the main peripheral and central mechanisms involved in weight regain. Gut hormone secretion profiles impact upon predisposition to weight regain according to an individual variability, although it is recognised a usual pattern of compensatory changes: a reduction in anorectic hormones secretion and an increase in orexigenic hormone. These changes lead to both increased appetite and reward value of food leading to increased energye intake. In addition, resting energy expenditure after weight loss is lower than expected according to body composition changes. This gap between observed and predicted energy expenditure following weight loss is named metabolic adaptation, which has been suggested to explain partly weight regain. This complicated scenario, beyond patient motivation, makes weight regain a challenge in long-term management interventions in patients with obesity.

Seroprevalence of SARS-CoV-2 antibodies in people with an acute loss in their sense of smell and/or taste in a community-based population in London, UK: An observational cohort study.

BACKGROUND: Loss of smell and taste are commonly reported symptoms associated with coronavirus disease 2019 (COVID-19); however, the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in people with acute loss of smell and/or taste is unknown. The study aimed to determine the seroprevalence of SARS-CoV-2 antibodies in a community-based population with acute loss of smell and/or taste and to compare the frequency of COVID-19 associated symptoms in participants with and without SARS-CoV-2 antibodies. It also evaluated whether smell or taste loss are indicative of COVID-19 infection. METHODS AND FINDINGS: Text messages, sent via primary care centers in London, United Kingdom, invited people with loss of smell and/or taste in the preceding month, to participate. Recruitment took place between 23 April 2020 and 14 May 2020. A total of 590 participants enrolled via a web-based platform and responded to questions about loss of smell and taste and other COVID-19-related symptoms. Mean age was 39.4 years (SD ± 12.0) and 69.1% (n = 392) of participants were female. A total of 567 (96.1%) had a telemedicine consultation during which their COVID-19-related symptoms were verified and a lateral flow immunoassay test that detected SARS-CoV-2 immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies was undertaken under medical supervision. A total of 77.6% of 567 participants with acute smell and/or taste loss had SARS-CoV-2 antibodies; of these, 39.8% (n = 175) had neither cough nor fever. New loss of smell was more prevalent in participants with SARS-CoV-2 antibodies, compared with those without antibodies (93.4% versus 78.7%, p < 0.001), whereas taste loss was equally prevalent (90.2% versus 89.0%, p = 0.738). Seropositivity for SARS-CoV-2 was 3 times more likely in participants with smell loss (OR 2.86; 95% CI 1.27-6.36; p < 0.001) compared with those with taste loss. The limitations of this study are the lack of a general population control group, the self-reported nature of the smell and taste changes, and the fact our methodology does not take into account the possibility that a population subset may not seroconvert to develop SARS-CoV-2 antibodies post-COVID-19. CONCLUSIONS: Our findings suggest that recent loss of smell is a highly specific COVID-19 symptom and should be considered more generally in guiding case isolation, testing, and treatment of COVID-19. TRIALS REGISTRATION: ClinicalTrials.gov NCT04377815.

Obesity Management Task Force of the European Association for the Study of Obesity Released "Practical Recommendations for the Post-Bariatric Surgery Medical Management".

Bariatric patients may face specific clinical problems after surgery, and multidisciplinary long-term follow-up is usually provided in specialized centers. However, physicians, obstetricians, dieticians, nurses, clinical pharmacists, midwives, and physical therapists not specifically trained in bariatric medicine may encounter post-bariatric patients with specific problems in their professional activity. This creates a growing need for dissemination of first level knowledge in the management of bariatric patients. Therefore, the Obesity Management Task Force (OMTF) of the European Association for the Study of Obesity (EASO) decided to produce and disseminate a document containing practical recommendations for the management of post-bariatric patients. The list of practical recommendations included in the EASO/OMTF document is reported in this brief communication.

Obesity, body weight regulation and the brain: insights from fMRI.

Obesity constitutes a major global health threat. Despite the success of bariatric surgery in delivering sustainable weight loss and improvement in obesity-related morbidity, effective non-surgical treatments are urgently needed, necessitating an increased understanding of body weight regulation. Neuroimaging studies undertaken in people with healthy weight, overweight, obesity and following bariatric surgery have contributed to identifying the neurophysiological changes seen in obesity and help increase our understanding of the mechanisms driving the favourable eating behaviour changes and sustained weight loss engendered by bariatric surgery. These studies have revealed a key interplay between peripheral metabolic signals, homeostatic and hedonic brain regions and genetics. Findings from brain functional magnetic resonance imaging (fMRI) studies have consistently associated obesity with an increased motivational drive to eat, increased reward responses to food cues and impaired food-related self-control processes. Interestingly, new data link these obesity-associated changes with structural and connectivity changes within the central nervous system. Moreover, emerging data suggest that bariatric surgery leads to neuroplastic recovery. A greater understanding of the interactions between peripheral signals of energy balance, the neural substrates that regulate eating behaviour, the environment and genetics will be key for the development of novel therapeutic strategies for obesity. This review provides an overview of our current understanding of the pathoaetiology of obesity with a focus upon the role that fMRI studies have played in enhancing our understanding of the central regulation of eating behaviour and energy homeostasis.

Practical Recommendations of the Obesity Management Task Force of the European Association for the Study of Obesity for the Post-Bariatric Surgery Medical Management.

Bariatric surgery is today the most effective long-term therapy for the management of patients with severe obesity, and its use is recommended by the relevant guidelines of the management of obesity in adults. Bariatric surgery is in general safe and effective, but it can cause new clinical problems and is associated with specific diagnostic, preventive and therapeutic needs. For clinicians, the acquisition of special knowledge and skills is required in order to deliver appropriate and effective care to the post-bariatric patient. In the present recommendations, the basic notions needed to provide first-level adequate medical care to post-bariatric patients are summarised. Basic information about nutrition, management of co-morbidities, pregnancy, psychological issues as well as weight regain prevention and management is derived from current evidences and existing guidelines. A short list of clinical practical recommendations is included for each item. It remains clear that referral to a bariatric multidisciplinary centre, preferably the one performing the original procedure, should be considered in case of more complex clinical situations.

Potential Mechanisms Mediating Sustained Weight Loss Following Roux-en-Y Gastric Bypass and Sleeve Gastrectomy.

Bariatric surgery is the only effective treatment for severe obesity. Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), the most commonly performed procedures, lead to sustained weight loss, improvements in obesity-related comorbidities and reduced mortality. In humans, the main driver for weight loss following RYGB and SG is reduced energy intake. Reduced appetite, changes in subjective taste and food preference, and altered neural response to food cues are thought to drive altered eating behavior. The biological mediators underlying these changes remain incompletely understood but changes in gut-derived signals, as a consequence of altered nutrient and/or biliary flow, are key candidates.

Reported appetite, taste and smell changes following Roux-en-Y gastric bypass and sleeve gastrectomy: Effect of gender, type 2 diabetes and relationship to post-operative weight loss.

Reduced energy intake drives weight loss following Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) procedures. Post-operative changes in subjective appetite, taste, and smell and food preferences are reported and suggested to contribute to reduced energy intake. We aimed to investigate the prevalence of these changes following RYGB and SG and to evaluate their relationship with weight loss. 98 patients post-RYGB and 155 post-SG from a single bariatric centre were recruited to a cross-sectional study. Participants completed a questionnaire, previously utilised in post-operative bariatric patients, to assess the prevalence of post-operative food aversions and subjective changes in appetite, taste and smell. Anthropometric data were collected and percentage weight loss (%WL) was calculated. The relationship between food aversions, changes in appetite, taste and smell and %WL was assessed. The influence of time post-surgery, gender and type 2 diabetes (T2D) were evaluated. Following RYGB and SG the majority of patients reported food aversions (RYGB = 62%, SG = 59%), appetite changes (RYGB = 91%, SG = 91%) and taste changes (RYGB = 64%, SG = 59%). Smell changes were more common post-RYGB than post-SG (RYGB = 41%, SG = 28%, p = 0.039). No temporal effect was observed post-RYGB. In contrast, the prevalence of appetite changes decreased significantly with time following SG. Post-operative appetite changes associated with and predicted higher %WL post-SG but not post-RYGB. Taste changes associated with and predicted higher %WL following RYGB but not post-SG. There was no gender effect post-RYGB. Post-SG taste changes were less common in males (female = 65%, males = 40%, p = 0.008). T2D status in females did not influence post-operative subjective changes. However, in males with T2D, taste changes were less common post-SG than post-RYGB together with lower %WL (RYGB = 27.5 ± 2.7, SG = 14.6 ± 2.1, p = 0.003). Further research is warranted to define the biology underlying these differences and to individualise treatments.

Converging indications of aldosterone antagonists (spironolactone and eplerenone): a narrative review of safety profiles.

The converging clinical effectiveness of mineralocorticoid receptor antagonists (MRAs) Spironolactone and Eplerenone has made their safety profiles/cost-effectiveness key determinants of "agents of choice" across a broad range of clinical indications. The clinical biology of the aldosterone molecule and its range of effects in varied organ systems have been well elucidated from recent mechanistic and systematic studies. Clinical experience with Spironolactone is well established, as is its adverse effects profile. The range of adverse effects experienced with Spironolactone subsequently led to its modification and synthesis of Eplerenone. Recent published reports have confirmed lower prevalence rates of sex-related adverse effects attributable to Eplerenone compared to Spironolactone. There is, however, not much to choose between these agents in regards to other adverse effects including hyperkalemia and kidney failure. As was the experience with Spironolactone, as more robust observational data on Eplerenone accrues, it is possible that the real-life experience of its adverse profile may be discordant with that reported by randomized controlled clinical trials (RCTs). In addition, its metabolism by the vulnerable and highly polymorphic cytochrome dependent pathway also makes it susceptible to various drug interactions. The potential implication of the latter (including morbidity and mortality) may take years to evolve.