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Abstract Context Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disorder in which previous reports have described obesity and a metabolic syndrome. Objective We describe the endocrine and metabolic characteristics of a large BBS population compared with matched control subjects. Design We performed a case-control study. Setting This study was performed at a hospital clinic. Patients Study patients had a clinical or genetic diagnosis of BBS. Main Outcome Measurements Our study determined the prevalence of a metabolic syndrome in our cohort. Results A total of 152 subjects were studied. Eighty-four (55.3%) were male. Mean (± standard deviation) age was 33.2 ± 1.0 years. Compared with age-, sex-, and body mass index–matched control subjects, fasting glucose and insulin levels were significantly higher in subjects with BBS (glucose: BBS, 5.2 ± 1.2 mmol/L vs control, 4.9 ± 0.9 mmol/L, P = 0.04; insulin: BBS, 24.2 ± 17.0 pmol/L vs control, 14.2 ± 14.8 pmol/L, P < 0.001). Serum triglycerides were significantly higher in subjects with BBS (2.0 ± 1.2 mmol/L) compared with control subjects (1.3 ± 0.8 mmol/L; P < 0.001), but total cholesterol, high-density lipoprotein, and low-density lipoprotein were similar in both groups. Systolic blood pressure was higher in the BBS group (BBS, 135 ± 18 mm Hg vs control subjects, 129 ± 16 mm Hg; P = 0.02). Alanine transaminase was raised in 34 (26.8%) subjects with BBS, compared with five (8.9%) control subjects (P = 0.01). The rate of metabolic syndrome, determined using International Diabetes Federation criteria, was significantly higher in the BBS group (54.3%) compared with control subjects (26% P < 0.001). Twenty-six (19.5%) of male subjects with BBS were hypogonadal (serum testosterone, 9.9 ± 5.3 mmol/L), but significant pituitary abnormalities were uncommon. Subclinical hypothyroidism was present in 24 of 125 (19.4%) patients with BBS, compared with 3 of 65 (4.6%) control subjects (P = 0.01). Conclusions Insulin resistance and the metabolic syndrome are increased in adult patients with BBS compared with matched control subjects. Increased subclinical hypothyroidism in the BBS cohort needs further investigation. A large case-control study examined endocrine and metabolic characteristics in adult BBS. Insulin resistance and metabolic syndrome were significantly more prevalent in BBS.

ObjectivesTo investigate the perceptions, attitudes, behaviours and potential barriers to effective obesity care in the UK using data collected from people with obesity (PwO) and healthcare professionals (HCPs) in the Awareness, Care, and Treatment In Obesity maNagement–International Observation (ACTION-IO) study.DesignUK’s PwO (body mass index of ≥30 kg/m2 based on self-reported height and weight) and HCPs who manage patients with obesity completed an online survey.ResultsIn the UK, 1500 PwO and 306 HCPs completed the survey. Among the 47% of PwO who discussed weight with an HCP in the past 5 years, it took a mean of 9 years from the start of their struggles with weight until a discussion occurred. HCPs reported that PwO initiated 35% of weight-related discussions; PwO reported that they initiated 47% of discussions. Most PwO (85%) assumed full responsibility for their own weight loss. The presence of obesity-related comorbidities was cited by 76% of HCPs as a top criterion for initiating weight management conversations. The perception of lack of interest (72%) and motivation (61%) in losing weight was reported as top reasons by HCPs for not discussing weight with a patient. Sixty-five per cent of PwO liked their HCP bringing up weight during appointments. PwO reported complex and varied emotions following a weight loss conversation with an HCP, including supported (36%), hopeful (31%), motivated (23%) and embarrassed (17%). Follow-up appointments were scheduled for 19% of PwO after a weight discussion despite 62% wanting follow-up.ConclusionsThe current narrative around obesity requires a paradigm shift in the UK to address the delay between PwO struggling with their weight and discussing weight with their HCP. Perceptions of lack of patient interest and motivation in weight management must be challenged along with the blame culture of individual responsibility that is prevalent throughout society. While PwO may welcome weight-related conversations with an HCP, they evoke complex feelings, demonstrating the need for sensitivity and respect in these conversations.Trial registration numberNCT03584191.

There is a global obesity epidemic that will continue to be a financial burden on healthcare systems around the world. Tackling obesity through diet and exercise should always be the first intervention, but this has not proved to be effective for a large number of patients. Pharmacotherapeutic options have been limited and many previously available drugs have been withdrawn due to safety concerns. Currently, only bariatric surgery has the capability to induce both substantial and durable weight loss. This article briefly reviews the history of pharmacotherapy for obesity before focusing on the clinical trial evidence for the use of the GLP-1 agonist liraglutide as a weight loss agent and comparing its efficacy with other emerging drug therapies for obesity.

Introduction The health of the United Kingdom workforce is key; approximately 186 million days are lost to sickness each year. Obesity and type 2 diabetes (T2D) remain major global health challenges. The aim of this retrospective service evaluation was to assess the impact of a digitally enabled, time‐restricted eating (TRE) intervention (Roczen Program, Reset Health Ltd) on weight and other health‐related outcomes. Methods This service evaluation was conducted in people living with overweight/obesity, with 89% referred from public sector employers. Participants were placed on a TRE, low‐carbohydrate, moderate protein plan delivered by clinicians and mentors with regular follow up, dietary guidance, goal setting, feedback, and social support. Results A total of 660 members enrolled and retention was 41% at 12 months. The majority were female (73.2%), 58.9% were of White ethnicity, with a mean (SD) age of 47.5 years (10.1), and a body mass index of 35.0 kg/m2 (5.7). Data were available for 82 members at 12‐month. At 12‐month, members mean actual and percentage weight loss was −9.0 kg (7.0; p < 0.001) and −9.2% (6.7, p < 0.001) respectively and waist circumference reduced by −10.3 cm (10.7 p < 0.001), with 45.1% of members achieving ≥10% weight loss. Glycated hemoglobin was significantly improved at 6 months in people living with T2D (−11 mmol/mol [5.7] p = 0.012). Binge eating score significantly reduced (−4.4 [7.0] p = 0.006), despite cognitive restraint increasing (0.37 [0.6] p = 0.006). Conclusion Our service evaluation showed that the Roczen program led to clinically meaningful improvements in body weight, health‐related outcomes and eating behaviors that were sustained at 12‐month. This service evaluation showed the efficacy of the Roczen program in public sector workers living with overweight and obesity.

The 10th Cardiovascular Outcome Trial (CVOT) Summit: Congress on Cardiovascular, Kidney, and Metabolic Outcomes was held virtually on December 5–6, 2024. This year, discussions about cardiovascular (CV) and kidney outcome trials centered on the recent findings from studies involving empagliflozin (EMPACT-MI), semaglutide (STEP-HFpEF-DM and FLOW), tirzepatide (SURMOUNT-OSA and SUMMIT), and finerenone (FINEARTS-HF). These studies represent significant advances in reducing the risk of major adverse cardiovascular events (MACE) and improving metabolic outcomes in heart failure with preserved ejection fraction (HFpEF), chronic kidney disease (CKD), and obstructive sleep apnea (OSA). The congress also comprised sessions on novel and established therapies for managing HFpEF, CKD, and obesity; guidelines for managing CKD and metabolic dysfunction-associated steatotic liver disease (MASLD); organ crosstalk and the development of cardio-kidney-metabolic (CKM) syndrome; precision medicine and person-centered management of diabetes, obesity, cardiovascular disease (CVD) and CKD; early detection of type 1 diabetes (T1D) and strategies to delay its onset; continuous glucose monitoring (CGM) and automated insulin delivery (AID); cardiovascular autonomic neuropathy (CAN) and the diabetic heart; and the role of primary care in the early detection, prevention and management of CKM diseases. The contribution of environmental plastic pollution to CVD risk, the increasing understanding of the efficacy and safety of incretin therapies in the treatment of CKM diseases, and the latest updates on nutrition strategies for CKM management under incretin-based therapies were also topics of interest for a vast audience of endocrinologists, diabetologists, cardiologists, nephrologists and primary care physicians, who actively engaged in online discussions. The 11th CVOT Summit will be held virtually on November 20–21, 2025 ( http://www.cvot.org ).

Pancreatic polypeptide (PP) is a gut hormone released from the pancreas in response to food ingestion and remains elevated for up to 6 h postprandially. Plasma levels are elevated in patients with pancreatic tumours. An intravenous infusion of PP has been reported to reduce food intake in man, suggesting that PP is a satiety hormone. We investigated whether a lower infusion rate of PP would induce significant alterations in energy intake. The study was randomised and double-blinded. Fourteen lean fasted volunteers (five men and nine women) received 90 min infusions of PP (5 pmol/kg per min) and saline on two separate days. The dose chosen was half that used in a previous human study which reported a decrease in appetite but at supra-physiological levels of PP. One hour after the end of the infusion, a buffet lunch was served and energy intake measured. PP infusion was associated with a significant 11 % reduction in energy intake compared with saline (2440 (se 200) v. 2730 (se 180) kJ; P < 0·05). Preprandial hunger as assessed by a visual analogue score was decreased in the PP-treated group compared to saline. These effects were achieved with plasma levels of PP within the pathophysiological range of pancreatic tumours.

Introduction Metabolic and bariatric surgery (MBS) has been an established treatment option for patients with Type 2 diabetes mellitus (T2DM), but there is a relative paucity of evidence-based guidelines on preoperative, operative, and postoperative considerations concerning metabolic surgery for T2DM patients. To address this gap, we initiated a Delphi consensus process with a diverse group of international multidisciplinary experts. Method We embarked on a Delphi consensus-building exercise to propose an evidence-based expert consensus covering various aspects of MBS in patients with T2DM. We defined the scope of the exercise and proposed statements and surveyed the literature through electronic databases. The literature summary and voting process were conducted by 52 experts, who evaluated 44 statements. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. Results Consensus, defined as > 80% agreement, was reached for 43 out of 44 statements. The experts reached an agreement on the nature, terminology, and mechanisms of action of MBS. The currently available scores for predicting remission of T2DM after surgery are not robust enough for routine clinical use, and there is a need for further research to enable more personalized treatment. Additionally, they agreed that metabolic surgery for T2DM is cost-effective, and MBS procedures for treating T2DM vary in their safety and efficacy. Conclusion This Delphi expert consensus statement guides clinicians on various aspects of metabolic surgery for T2DM and also grades the quality of the available evidence for each of the proposed statements.

IntroductionIn the UK and Ireland, severe and complex obesity is managed in specialist weight management services (SWMS), which provide multicomponent lifestyle interventions to support weight loss, and use of medication if available. Liraglutide 3 mg (LIRA 3 mg) is an effective weight-loss medication, but weight loss in individual patients is variable, and its efficacy has not been assessed in SWMS. This study aims to investigate whether a targeted prescribing pathway for LIRA 3 mg with multiple prespecified stopping rules could help people with severe obesity and established complications achieve ≥15% weight loss in order to determine whether this could be considered a clinically effective and cost-effective strategy for managing severe and complex obesity in SWMS.Methods and analysisIn this 2-year, multicentre, open-label, real-world randomised controlled trial, 384 adults with severe and complex obesity (defined as body mass index ≥35 kg/m2 plus either prediabetes, type 2 diabetes, hypertension or sleep apnoea) will be randomised via a 2:1 ratio to receive either standard SWMS care (n=128) or standard SWMS care plus a targeted prescribing pathway for LIRA 3 mg with prespecified stopping rules at 16, 32 and 52 weeks (n=256).The primary outcome is to compare the proportion of participants achieving a weight loss of ≥15% at 52 weeks with a targeted prescribing pathway versus standard care. Secondary outcomes include a comparison of (1) the weight loss maintenance at 104 weeks and (2) the budget impact and cost effectiveness between the two groups in a real-world setting.Ethics and disseminationThe Health Research Authority and the Medicines and Healthcare products Regulatory Authority in UK, the Health Products Regulatory Authority in Ireland, the North West Deanery Research Ethics Committee (UK) and the St Vincent’s University Hospital European Research Ethics Committee (Ireland) have approved the study. The findings of the study will be published in peer-reviewed journals.Trial registration numberClinicalTrials.gov—Identifier: NCT03036800.European Clinical Trials Database—Identifier: EudraCT Number 2017-002998-20.

Background/Objectives: The STRIVE study was a multicentre, open-label, real-world clinical trial evaluating the effectiveness of a targeted prescribing pathway for liraglutide 3.0 mg as an adjunct to standard care versus standard care alone in people with obesity attending Specialist Weight Management Services (SWMS) in the UK and Ireland. This post hoc analysis focuses on the standard care arm to explore differences in outcomes between sites, particularly the potential impact of offering meal replacements as part of usual care. Methods: Participants included individuals with a BMI ≥ 35 kg/m² and at least one obesity-related complication who received standard care at five SWMS sites. All sites provided specialist nutrition and exercise counselling; however, only the Dublin site (n = 40) included meal replacements as part of routine care. Baseline characteristics and weight change data were compared between the Dublin and UK cohorts (n = 92) at 52 and 104 weeks. Statistical comparisons were made using appropriate parametric and non-parametric tests. Results: At baseline, the Dublin cohort was significantly older (p < 0.01), had a higher prevalence of hypertension (p < 0.05), and a lower reported incidence of depression/anxiety (p < 0.05) than the UK cohort. At week 52, the Dublin group achieved greater mean weight loss (−6.1%, SD ± 5.7%) compared to the UK cohort (−1.3%, SD ± 6.7%, n = 27, p < 0.01). By week 104, Dublin participants maintained a mean weight loss of −4.4% (SD ± 5.7%) while UK participants had a mean weight gain of 0.37% (SD ± 7.6%) (p < 0.05). Conclusions: The integration of meal replacements as part of usual care may have contributed to the greater and sustained weight loss observed in the Dublin cohort compared to other SWMS in the UK.

People of Black African and Black Caribbean ethnicity experience higher rates and poorer outcomes of type 2 diabetes (T2D) than people of White European ethnicity; these inequalities are compounded by poor healthcare access. Cultural tailoring of diabetes self-management education and support (DSMES) programs has the potential to improve healthcare engagement and clinical outcomes for ethnic minority groups. Healthy Eating & Active Lifestyles for Diabetes (HEAL-D) is a co-designed, culturally tailored group-based DSMES program for adults of Black African and Black Caribbean ethnicity. This trial aims to evaluate the clinical and cost effectiveness of the HEAL-D intervention, compared to standard DSMES programs, in Black African and Black Caribbean adults living with T2D. A 24-month, multicenter, pragmatic, open-label, 2-arm, parallel-group, individually randomized group treatment trial will be conducted, with primary end point (glycated hemoglobin [HbA ]) assessment at 12 months. Black African and Black Caribbean adults with T2D (n=300), recruited from 3 to 5 centers in the United Kingdom (including London, West Midlands, and Greater Manchester), will be randomized in a 1:1 ratio to HEAL-D (intervention) or a standard DSMES program (control). HbA , blood lipids, anthropometric outcomes, blood pressure, physical activity, and patient-reported outcome measures relating to psychological well-being and self-management support, lifestyle behaviors, and health economics will be collected at baseline and follow-up visits (6, 12, and 24 months). Cost-effectiveness will be assessed through a cost-utility analysis conducted from a health and social care perspective. A mixed methods process evaluation will provide a formative evaluation of delivery, intervention fidelity, and implementation of HEAL-D, and an embedded study within a project will assess the impact of multiple long-term conditions on uptake of, and engagement with HEAL-D, and the impact of HEAL-D on multiple long-term conditions. The trial received Research Authority and Research Ethics Council approval on April 22, 2024. Funding began in August 2023. Site \"green light\" was received on August 15, 2024, for London; November 29, 2024, for Manchester; and January 31, 2025, for the West Midlands. Recruitment commenced in August 2024 and is due to run for 11 months. As of March 26, 2025, a total of 76 participants have consented. Last patient, last visit is expected in June 2027; primary data analysis is expected to begin in July 2027. Final results are anticipated to be available in September 2027, and publication is expected by the end of 2027. The HEAL-D trial will address whether a culturally tailored DSMES program, provided in-person or via videoconferencing, is clinically and cost-effective compared to standard DSMES at improving diabetes management in Black African and Black Caribbean adults. If effective, this would provide an evidence-based model of equitable DSMES services and improve the implementation of healthcare programs for ethnic minority groups. ISRCTN 1434448; https://www.isrctn.com/ISRCTN14344948. DERR1-10.2196/71861.