BACKGROUND:Fast Track to Health was a 12-month intervention for adolescents with obesity and associated complications. Adolescents followed a very low-energy diet (VLED) and intermittent (IER) or continuous energy restriction (CER). This study explored adolescents', parents', and dietitians' perspectives of the intervention. METHODS:A convergent parallel mixed-methods evaluation was conducted. Acceptability questionnaires were collected from adolescents (Week-16: n=113, Week-52: n=88) and parents (Week-16: n=108, Week-52: n=80). Semi-structured interviews were conducted with adolescents (n=14), parents (n=11), and dietitians (n=6) at Week-52. Interview transcripts were thematically analysed. RESULTS:Adolescents rated enjoyability (score 0-100) at Week-16 [Mean (SD) IER: 63.5 (21.1) vs. CER: 65.9 (20.2), p=0.550] and Week-52 [IER: 67.2 (18.1) vs. CER: 61.0 (23.4), p=0.198], showing no significant difference between groups. Most parents reported benefits at Week-16 (IER: 86% vs. CER: 93%, p=0.263) and Week-52 (IER: 79% vs. CER: 83%, p=0.717). Adolescents positively rated their experience with dietitians. Qualitative feedback emphasized the impact of clear dietary advice, easy and frequent access to support, continuity of care, and family engagement. CONCLUSIONS:This evaluation offers insights into a specialised dietary intervention for adolescents. Findings can inform future obesity treatments for adolescents in outpatient tertiary healthcare settings.
BACKGROUND:Childhood overweight and obesity represent a growing global public health challenge. Given the substantial socioeconomic heterogeneity across Asia, a systematic assessment of the disease burden attributable to high body mass index (BMI) in children and its evolving characteristics is critical. Within the GBD 2023 risk attribution framework for children, asthma is the only disease outcome currently included. Therefore, this study focuses on the asthma burden attributable to high BMI in children. OBJECTIVE:To systematically analyze the trends and characteristics of asthma burden attributable to high BMI among children aged 0 14 years in Asia from 1990 to 2050. METHODS:Data on the number of disability-adjusted life years (DALYs) and crude DALY rates (CDR) for asthma attributable to high BMI among children in Asian were obtained from the Global Burden of Disease Study (GBD) 2023. Trends were measured using estimated annual percentage change (EAPC), and future projections were made with a Bayesian age-period-cohort (BAPC) model. Spearman's correlation assessed the link between disease burden and the Socio-Demographic Index (SDI), and a decomposition analysis examined drivers of DALY changes. RESULTS:Children in East Asian had the highest CDR for asthma attributable to high BMI (16.28/100,000) in 2023 and experienced the largest increase from 1990 to 2023 (EAPC=1.57%/year), with future trends projected to rise through 2023-2050 (EAPC=4.49%/year). In high-income Asia Pacific, the 2023 CDR (14.49/100,000) reflected a steady decline since 1990 (EAPC=-0.82%/year). Children in South Asian had the lowest CDR (1.94/100,000). In most countries and territories, the increase in CDR was greater among girls than boys, a sex disparity particularly pronounced in South Asia and Southeast Asia. SDI was positively correlated with the CDR (ρ=0.54, P<0.001) and its EAPC during 1990-2023 (ρ=0.33, P=0.021). Decomposition analysis showed epidemiological change as the main driver of East Asia's rising burden. CONCLUSION:The high BMI-attributed asthma burden in children is most severe and rising fastest in East Asia, while South and Southeast Asia show pronounced sex disparities. These findings provide an epidemiological foundation for targeted prevention and control strategies.
Objective Pediatric obesity is associated with early metabolic complications and increased risk of persistent obesity in adulthood. Beyond fat accumulation, obesity may induce long-lasting molecular alterations in adipose tissue, described as "obesogenic memory." However, whether such intrinsic alterations are already present in pediatric adipose progenitor cells remains poorly understood. This study aimed to develop an in vitro model of adipogenesis using pediatric adipose-derived mesenchymal stem cells (hMSCs) and to investigate whether obesity is associated with intrinsic metabolic reprogramming of adipose progenitors. Methods hMSCs were isolated from periumbilical subcutaneous adipose tissue obtained from pediatric subjects with normal weight (NW), overweight (OW) and obesity (OB). Cells were expanded and induced to undergo adipogenic differentiation for up to 14 days using defined adipogenic media. Differentiation was evaluated through morphological analysis, lipid accumulation (BODIPY staining), gene expression profiling by RT-qPCR, and protein analysis by Western blot. Results Two differentiation protocols efficiently induced adipocyte maturation without cytotoxicity. hMSCs derived from NW and OB subjects showed comparable adipogenic differentiation capacity, with similar lipid droplet accumulation and expression of canonical adipogenic markers including C/EBPα, PPARγ, and FABP4. Despite this comparable differentiation efficiency, OB-derived adipocytes exhibited altered transcriptional regulation of genes involved in lipid metabolism, including pathways associated with lipogenesis, lipolysis, and fatty acid β-oxidation. Protein analyses further revealed dysregulated expression of key metabolic regulators such as SCD1, SREBP1, PNPLA2, and FADS1, suggesting altered lipid metabolic programming. Conclusions Pediatric obesity does not impair adipogenic differentiation but is associated with intrinsic metabolic alterations in adipose progenitor cells. These findings support the presence of an early obesogenic memory in adipose tissue that may contribute to long-term metabolic dysfunction.
Background: The 2024 European Association for the Study of Obesity (EASO) framework redefines obesity by incorporating central adiposity and morbidity. However, the phenotypic characterization of risk heterogeneity across the full BMI spectrum under this framework—and its prognostic implications for mortality and cardiovascular outcomes—remain to be elucidated. Therefore, we aimed to evaluate the ability of this new framework to improve phenotypic stratification and describe risk heterogeneity across BMI categories. Methods and Results: In 451,615 UK Biobank participants (median follow-up, 15.1 years), obesity was defined using (1) the EASO framework (which reclassifies individuals with BMI 25–<30 kg/m² into 'EASO overweight' [WHtR <0.5 and/or absence of morbidity] and 'EASO new obesity' [WHtR ≥0.5 and the presence of at least one morbidity]), and (2) an extended EASO framework incorporating morbidity stratification across all BMI categories. Cox proportional hazards models estimated hazard ratios (HRs) for all-cause mortality and major adverse cardiovascular events (MACE). Applying the EASO framework reclassified 15.62% of individuals previously categorized as having overweight into the category of people with obesity. Consequently, the prevalence of obesity increased from 24.50% to 40.12%. Two distinct risk patterns emerged: all-cause mortality showed a V-shaped association across adiposity categories, whereas MACE risk increased linearly with higher adiposity. Compared with normal weight, EASO overweight had the lowest mortality (HR 0.82 [95% CI, 0.80–0.84]), while EASO new obesity showed a comparable risk (0.96 [0.94–0.99]). The highest mortality risk was observed in BMI obesity (1.05 [1.02–1.08]). For MACE, EASO overweight had no excess risk (1.04 [0.99–1.09]), whereas both EASO new obesity and BMI obesity faced the highest and most substantial risks, with HRs of 1.35 (1.29–1.42) and 1.38 (1.32–1.45), respectively. When stratified by morbidity, the V-shaped mortality association was preserved and MACE risk remained linear. Individuals with morbidity consistently exhibited higher risks across all adiposity categories, indicating a vertical shift in risk rather than a change in association shape. Conclusions: The EASO framework substantially increases obesity prevalence and better identifies individuals with adverse metabolic and cardiovascular profiles. Morbidity does not alter the overall pattern of mortality and cardiovascular risk across adiposity levels but consistently amplifies absolute risk, supporting a morbidity-integrated approach to obesity phenotyping and risk assessment.
INTRODUCTION:The relationship between sleep-disordered breathing (SDB), bone mineral density (BMD), and risk of osteoporosis is unclear. Obesity, a condition often comorbid with SDB, has been associated with high BMD, yet its impact on bone health remains controversial. The purpose of this study was to evaluate the implications of obesity in the relationship between SDB and BMD. METHODS:A total of 225 adults aged 20-65 years were enrolled in this study. Participants were nonsmokers, free of major cardiovascular diseases, and not receiving treatment for SDB. Participants completed overnight polysomnography and whole-body dual-energy X-ray absorptiometry (DEXA) scans. SDB was defined as apnea-hypopnea index of ≥5 events/hour. Total body BMD (g/cm2), T scores, and Z scores were obtained from DEXA scans. Height and weight measures were collected for computation of body mass index (BMI, kg/m2). Multivariable linear regression analysis was conducted to test the association between SDB and BMD metrics and the contribution of relevant covariates. RESULTS:Participants with SDB (n = 74, 32.9% of the sample) had higher total-body BMD (p = 0.003), T score (p = 0.017), and Z score (p = 0.011) compared to non-SDB controls. In multivariable models adjusted for demographic characteristics, SDB was not significantly associated with total-body bone measures. However, when including BMI, significant inverse relationships between SDB and total body BMD (p = 0.046), T score (p = 0.049), and Z score (p = 0.049) became apparent. Such associations persisted after controlling for lifestyle, clinical and sleep variables (fully adjusted models, total BMD, p = 0.036; T score, p = 0.037; Z score, p = 0.034). In sensitivity analysis, there were no associations between SDB and bone measures in models adjusted for body fat in lieu of BMI. CONCLUSION:An inverse, albeit modest, association between SDB and BMD exists, and this relationship emerges when considering BMI but not body fat. Hence, our data suggest that elevated body mass rather than adiposity may mask the negative association between SDB and bone health, thus possibly explaining prior conflicting evidence. Longitudinal investigations corroborating these findings and evaluating their implications for osteoporosis risk in patients with SDB are needed.
Introduction: Obesity is a major risk factor for obstructive sleep apnea (OSA), and weight loss induced by glucagon-like peptide-1 receptor agonists has been associated with reductions in the apnea–hypopnea index (AHI). Case Presentation: We report a 35-year-old obese man with severe OSA who received tirzepatide for 12 months during the SURMOUNT-OSA trial. His body-mass index decreased from 31.0 to 24.9 kg/m², and AHI decreased from 54.8 to 4.4 events/h. Endotypic traits demonstrated improved upper-airway patency, increased compensatory pharyngeal muscle responsiveness, reduced loop gain, and a lower arousal threshold, accompanied by paradoxically longer event duration. Conclusion: This case suggests that tirzepatide improves OSA through weight loss as well as favourable shifts in airway physiology and ventilatory control. Glucagon-like peptide-1–based therapy may represent a promising treatment for obesity-related OSA, warranting further mechanistic studies.
Background: Cardiovascular–kidney–metabolic (CKM) syndrome refers to a multi-systemic condition with established pathophysiological connections between obesity, diabetes mellitus, chronic kidney disease (CKD), and cardiovascular disease (CVD). Chronic low-grade inflammation has been recognized as a common pathophysiological theme linking metabolic dysfunction to multisystem damage of the heart, kidneys, and vasculature. The aim of this narrative review is to summarize the major pharmacologic strategies that target inflammatory pathways in obesity and across the cardiovascular–kidney–metabolic (CKM) disease spectrum, including metabolic therapies with indirect anti-inflammatory effects and targeted immunomodulatory agents. Summary: New therapies have markedly changed the obesity and the CKM treatment paradigm, with evidence that currently available metabolic medications confer cardiovascular and renal benefits in addition to glycemic control or weight improvement. Nutrient-Stimulated Hormone (NuSH) therapies, and sodium–glucose cotransporter‐2 inhibitors (SGLT2i), work synergistically to positively modulate systemic inflammation while maintaining cardiovascular health and cardiometabolic function throughout therapy. Additionally, emerging clinical data for direct anti-inflammatory treatments, such as interleukin‐1β/interleukin‐6 inhibition and low‐dose colchicine, have established inflammation as a modifiable cardiovascular risk factor. Furthermore, therapies that target the liver such as resmetirom, fibroblast growth factor-21 (FGF21) analogues, and peroxisome proliferator-activated receptors (pan-PPAR) agonists, have highlighted the role of the liver–adipose axis in metabolic inflammation and CKM progression. Together, both metabolic and direct anti-inflammatory therapies represent the most recent evolution of a combined approach to treating metabolic dysfunction and inflammation. This type of approach has the potential to revolutionize the prevention and treatment of CKM across the spectrum of diseases and usher in personalized medicine for obesity-related cardiometabolic diseases. However, further studies are needed to determine when these therapies should be initiated, which patients are most likely to benefit, and whether combination approaches can alter disease progression beyond the current standard of care.
INTRODUCTION:Experiencing weight stigma negatively impacts health yet remains present in healthcare environments. Hospital environments must be inclusive for people living with obesity (PLwO). The aim of this study was to develop and refine a checklist to increase obesity inclusivity in UK National Health Service (UK NHS) hospital environments, with input from healthcare professionals (HCPs), researchers, PLwO, and their carers and family members (C/FM). METHODS:This study used a sequential mixed-methods approach. Phase 1 used a converging coding matrix to integrate existing checklists and reviewed language for inclusivity. In phase 2, HCPs, researchers, PLwO, and C/FM were recruited from professional and patient networks to provide feedback on the integrated checklist using a mixed-methods survey (February-March 2025) and qualitative semi-structured interviews (May-July 2025). Descriptive statistics and deductive and inductive framework analyses were used to identify patterns in the data to inform refinement of the checklist and implementation recommendations (Phase 3). RESULTS:Searches identified five checklists, which were integrated, resulting in categories for reading materials, furniture, equipment, and access and infrastructure. Sixty-nine participants completed the survey, and eighteen were interviewed. Overall, participants considered the checklist comprehensive. Integration of the qualitative survey and interview data resulted in four themes: (1) recommendations and thoughts about checklist components; (2) wording, language, images, and structure; (3) patient impact and care experiences; (4) implementation barriers and support. Primary implementation barriers related to funding, space, outdated infrastructure, and deep-rooted weight bias. Management buy-in, training, education, endorsement, and accreditation schemes were considered facilitators. Twenty recommendations were developed to support hospitals with implementation. CONCLUSION:Findings indicate that a clear, practical, and inclusive checklist could support hospitals in reducing weight stigma and improving care experiences for PLwO. The collaboratively developed and refined checklist offers a practical tool for hospitals to use. However, support will be required for effective and complete implementation.
Introduction: Bariatric surgery represents a highly effective intervention for individuals with severe obesity, yet the preoperative motivational factors influencing adherence and long-term outcomes remain insufficiently explored, particularly in the context of mental health. This study aimed to develop and validate a culturally tailored questionnaire to assess preoperative motivations among bariatric surgery candidates, thereby enhancing personalized care. Methods: A mixed-methods study conducted from 2017 to 2019 at Rasool-e-Akram Hospital, Tehran, Iran, enrolled 448 adults with severe obesity (BMI ≥ 40 kg/m² or ≥35 kg/m² with at least one comorbidity) . Semi-structured interviews (n=200) generated an initial 158-item pool, which was refined into a 94-item pilot questionnaire (n=100) and subsequently a final 30-item version (n=148). The validation process encompassed evaluations of content validity (via Content Validity Ratio [CVR] and Content Validity Index [CVI]), construct validity (through Exploratory Factor Analysis [EFA]), reliability (using Cronbach’s alpha), and convergent/divergent validity (employing the Treatment Self-Regulation Questionnaire [TSRQ] and Patient Health Questionnaire-9 [PHQ-9]). Results: The 30-item Bariatric Surgery Motivation Questionnaire encompasses four domains: Health (8 items), Physical Discomfort (4 items), Psychosocial Factors (12 items), and Attitudes Toward Surgery (6 items). EFA confirmed the factorial structure, accounting for 63.4% of variance (KMO=0.739, p<0.001). Content validity was strong (S-CVI/Ave=0.87; CVR>0.49). Overall reliability was satisfactory (α=0.813), with domain-specific alphas ranging from 0.312 to 0.807. Convergent validity with TSRQ (r=0.78, p<0.001) and divergent validity with PHQ-9 (r=-0.02, p=0.032) were supported. Conclusion: The Bariatric Surgery Motivation Questionnaire is a potentially valid and reliable instrument for evaluating preoperative motivations among bariatric surgery candidates. It provides clinicians with a practical means to identify motivational factors that may affect surgical outcomes. Further refinement of domains with lower reliability and validation in larger multicenter samples could enhance its clinical utility.
INTRODUCTION:The prevalence of overweight and obesity in children and adolescents continues to rise, and there is a lack of long-term follow-up to clarify health and well-being trajectories into adolescence and adulthood. This study investigated anthropometry and quality of life (QoL) trajectories in 7-14-year-old vulnerable children 3 years after attending a lifestyle camp. METHODS:Vulnerable children referred to a 10-week multicomponent lifestyle camp due to overweight or obesity, and/or psychosocial issues were enrolled. Anthropometry was assessed using bioelectric impedance and QoL using the Pediatric Quality of Life Inventory. Mixed-effects models were performed to assess longitudinal changes in anthropometry and QoL and explore if improvements achieved during the lifestyle intervention predicted long-term outcomes. RESULTS:In total, 222 participants (12.3 ± 1.4 years) were included, of which 126 (56%) participated in the 3-year follow-up (15.4 ± 1.3 years). Of those, 91 (72%) had anthropometry assessed, and the majority (83%) of participants were still living with overweight/obesity. Body mass index standard deviation score (BMI-SDS) was lower at 3 years (2.00 standard deviation [SD] ± 1.1) compared to baseline (2.48 SD ± 0.9). QoL remained higher at the 3-year follow-up compared to before the intervention. Compared to end-of-treatment, girls had an increase in BMI-SDS (0.37 SD [95% CI 0.26; 0.48]) and body fat (5.62% [95% CI 4.36; 6.88]) at the 3-year follow-up, while boys had a decrease in body fat (-2.25% [95% CI -3.87; -0.62]) but no change in BMI-SDS. Overall, QoL decreased (total QoL -8.33 [95% CI -10.73; -5.94]) during the post-intervention phase. CONCLUSION:The lifestyle camp, a child-centered intensive short-term multicomponent intervention focused on well-being, peer interaction, and social belonging, may be a promising treatment strategy for improving health and well-being long-term in vulnerable children, although the improvements attenuate across time. Future research should explore the potential to rethink treatment strategies and investigate whether continuous long-term support may help sustain improvements further throughout adolescence.
Introduction: Obesity is multifactorial and increasingly prevalent disease associated with chronic kidney disease (CKD). While cross-sectional studies support a link between adiposity and renal dysfunction, the long-term impact of total body fat on kidney function remains unclear. This study aims to evaluate the association between baseline adiposity, assessed by body mass index (BMI) and total body fat percentage, and renal function parameters, and to determine whether adiposity predicts CKD outcomes over 4 years in individuals without diabetes at low-to-moderate cardiovascular risk. Methods: This retrospective, multicenter study included 8,153 participants from the ILERVAS project in Lleida, Spain. Adiposity was measured using BMI and estimated body fat percentage (CUN-BAE formula). Renal function was evaluated by estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR). A subset of 3,222 individuals was reevaluated after 4 years. Multivariable regression models and ROC analysis were performed to explore associations and predictive performance. Results: CKD prevalence was 15.1%, higher in individuals with obesity (17.2%) than in those with overweight (13.7%) or normal weight (13.9%, p < 0.001). Body fat percentage showed a stronger inverse correlation with eGFR than BMI and was independently associated with eGFR decline. Baseline body fat percentage and its increase over time were associated with eGFR decline. Neither adiposity measure independently predicted CKD presence nor albuminuria. Conclusions: Higher total body fat is associated with impaired renal function and its progression over time, independently of traditional CKD risk factors. These findings support incorporating body fat assessment in CKD prevention beyond BMI-based strategies.
INTRODUCTION:We investigated how causal attributions - that is, individuals' beliefs about what caused their obesity - are associated with weight loss in a digital lifestyle intervention. METHODS:Data were collected from Healthy Weight Coaching, a 12-month real-world online intervention. Weight and height were self-reported. Body mass index (BMI) was calculated using interpolated weights at 3, 6, 9, and 12 months. At baseline, participants completed an eight-item questionnaire on causal attributions, rating each as playing no role, some role, or a major role. TwoStep cluster analysis grouped individuals with similar response profiles. RESULTS:Data were available for 1,834 participants (1,524 [83.1%] women, median age 52 years, median BMI 39.1 kg/m2). Participants most frequently attributed obesity to unhealthy dietary habits and lack of physical activity, whereas genetics, family lifestyle habits, and medication were least endorsed. Attributing obesity to stress (somewhat, standardized B = 0.156 [95% CI, 0.051-0.262]; very much, B = 0.204 [95% CI, 0.100-0.307]), fatigue (very much, B = 0.154 [95% CI, 0.073-0.235]), adversities in life (somewhat, B = 0.112 [95% CI, 0.041-0.184]; very much, B = 0.100 [95% CI, 0.024-0.176]), or medication (somewhat, B = 0.089 [95% CI, 0.022-0.155]; very much, B = 0.108 [95% CI, 0.025-0.192]) were associated with lower weight loss compared with those not endorsing these attributions. However, only stress ("very much") reached a small effect size according to Cohen's criteria, whereas the remaining associations were negligible in magnitude despite statistical significance. Cluster analysis revealed four clusters. Compared to those behaviourally focused, particularly endorsing dietary habits and physical activity, all other clusters showed higher endorsement of stress, fatigue, and adversities in life, with a cluster labelled multifactorial fully endorsing all eight items. Relative to behaviourally focused, all other clusters had lower odds of ≥5% weight loss and lost less weight (broad lifestyle oriented, B = 0.104 [95% CI, 0.032-0.177], p = 0.004; psychologically burdened, B = 0.144 [95% CI, 0.063-0.225], p < 0.001; multifactorial, B = 0.222 [95% CI, 0.136-0.308], p < 0.001). Only the multifactorial cluster reached a small effect size. CONCLUSIONS:Strong endorsement of stress as a cause of obesity and membership in the multifactorial cluster were associated with less favourable weight loss outcomes. However, effect sizes were small, suggesting limited standalone impact but potential relevance within broader behavioural and psychological treatment contexts.
Introduction Approximately one in five workers in Europe is engaged in shift work. Studies reveal that night shift work leads to an increased risk of overweight, obesity and related diseases. Yet, the biological and behavioural mechanisms underlying these associations are not fully understood. The cross-sectional and mechanistic studies within the European SHIFT2HEALTH project aim to investigate biological, behavioural and psychosocial key risk factors responsible for the association between night work and obesity across five European countries. Methods A multi-centric cross-sectional study is designed to unravel obesogenic risk factors, eating habits and sleep patterns in night shift workers and day workers from the health- and various industrial sectors. Recruitment takes place in Austria, Denmark, Germany, Poland, and the Netherlands, aiming at 500 night shift workers and 500 day workers. Anthropometric measurements, sensory perception and food preference tests are performed, alongside extensive questionnaires. In addition, biological samples (blood, hair, urine, faeces) are collected for biomarker measurements of inflammation, oxidative stress, glycaemic and lipaemic parameters, for microbiome and metabolomics analyses and chronotype assessment. In a nested mechanistic study, night shift workers (N=200) recruited in Austria and in the Netherlands, additionally collect urine samples from all voids over 24 hours during a day shift and a night shift, as well as dried blood spots and tongue swabs at four time points and undergo continuous sleep, activity and light exposure monitoring through actigraphy. The association between night shift work and its metrics with levels of pre-obesity biomarkers will be evaluated in crude and multivariable-adjusted regression models, adjusting for potential confounders. Stratified analyses by age, gender, sector and chronotype will be conducted. Conclusion In the cross-sectional and mechanistic studies of the SHIFT2HEALTH project, biological, behavioural and psychosocial factors of night shift workers will be compared with those of day workers across sectors. The outcomes of these studies will serve as a basis for future intervention studies and, together, will contribute to the development of strategies to prevent and reduce overweight and obesity with the aim to improve the health and wellbeing of night shift workers. Trial registration: clinicaltrials.gov, ID: NCT06288568
INTRODUCTION:We aimed to study the effects of the glucagon-like peptide-1 receptor agonist exenatide on behavioral outcomes in children and adolescents with obesity. METHODS:This study reports pre-specified secondary outcomes of a randomized, double-blind, placebo-controlled trial in adolescents with obesity, aged 10-18 years. Participants (n = 44) were randomized to 6 months treatment with exenatide or placebo, along with a lifestyle intervention consisting of nutritional advice from a dietitian and sessions with a psychologist to optimize physical activity. Change in choices of food and drink, portion sizes, meal frequency, sleep, screen time, and physical activity were assessed by 6-min walking test, accelerometry, and questionnaires. RESULTS:Exenatide treatment was associated with improved adherence to choices of recommended food and drinks (score change 4.34, 95% CI: 1.05-7.63, p = 0.01, Hedges' g 0.82, 95% CI: 0.17-1.49), decreased portion size (score change -4.05, 95% CI: -6.51 to -1.58, p = 0.002, Hedges' g -1.29, 95% CI: -2.13 to -0.45), and increased self-reported physical activity (1.82 h, 95% CI: 0.68-2.96, p = 0.002 Hedges' g 0.97, 95% CI: 0.33-1.62), while no differences in meal frequency, snacking, sleep, screen time, objectively measured physical fitness or activity were found. CONCLUSION:Exenatide treatment was associated with modest improvements in selected self-reported dietary behaviors, including improved adherence to recommended food and drink choices and reduced portion sizes, as well as increased self-reported physical activity, although no changes were observed in objective measures of physical activity or other lifestyle factors.
INTRODUCTION:The 2024 European Association for the Study of Obesity (EASO) framework redefines obesity by incorporating central adiposity and morbidity. However, the phenotypic characterization of risk heterogeneity across the full body mass index (BMI) spectrum under this framework - and its prognostic implications for mortality and cardiovascular outcomes - remain to be elucidated. Therefore, we aimed to evaluate the ability of this new framework to improve phenotypic stratification and describe risk heterogeneity across BMI categories. METHODS:In 451,615 UK Biobank participants (median follow-up, 15.1 years), obesity was defined using (1) the EASO framework (which reclassifies individuals with BMI 25 to <30 kg/m2 into "EASO overweight" [WHtR <0.5 and/or absence of morbidity] and "EASO new obesity" [WHtR ≥0.5 and the presence of at least one morbidity]), and (2) an extended EASO framework incorporating morbidity stratification across all BMI categories. Cox proportional hazards models estimated hazard ratios (HRs) for all-cause mortality and major adverse cardiovascular events (MACE). RESULTS:Applying the EASO framework reclassified 15.62% of individuals previously categorized as having overweight into the category of people with obesity. Consequently, the prevalence of obesity increased from 24.50% to 40.12%. Two distinct risk patterns emerged: all-cause mortality showed a V-shaped association across adiposity categories, whereas MACE risk increased linearly with higher adiposity. Compared with normal weight, EASO overweight had the lowest mortality (HR 0.82 [95% CI: 0.80-0.84]), while EASO new obesity showed a comparable risk (0.96 [0.94-0.99]). The highest mortality risk was observed in BMI obesity (1.05 [1.02-1.08]). For MACE, EASO overweight had no excess risk (1.04 [0.99-1.09]), whereas both EASO new obesity and BMI obesity faced the highest and most substantial risks, with HRs of 1.35 (1.29-1.42) and 1.38 (1.32-1.45), respectively. When stratified by morbidity, the V-shaped mortality association was preserved and MACE risk remained linear. Individuals with morbidity consistently exhibited higher risks across all adiposity categories, indicating a vertical shift in risk rather than a change in association shape. CONCLUSION:The EASO framework substantially increases obesity prevalence and better identifies individuals with adverse metabolic and cardiovascular profiles. Morbidity does not alter the overall pattern of mortality and cardiovascular risk across adiposity levels but consistently amplifies absolute risk, supporting a morbidity-integrated approach to obesity phenotyping and risk assessment.
INTRODUCTION:Bariatric metabolic surgery (BMS) alone or glucagon-like peptide-1 receptor agonists (GLP-1RA) alone are known to reduce major adverse cardiovascular events (MACEs). However, the benefit for primary prevention of MACE with use of GLP-1RA treatment after BMS is unclear. This retrospective cohort study assessed the associations of post-BMS GLP-1RA treatment with first incidence of MACE/all-cause mortality, as well as with predicted cardiovascular (CVD) risk and body mass index (BMI) and hemoglobin-A1c (HbA1c) levels, among patients with obesity and diabetes. METHODS:Adults who initiated GLP-1RA post-BMS were compared with individuals who did not. Groups were matched based on age, sex, BMI, HbA1c, years since BMS, and the nearest-neighbor propensity score for the probability of receiving GLP-1RA. Follow-up began at GLP-1RA initiation and ended on December 31, 2023. RESULTS:The study population included 476 GLP-1RA initiators and 952 matched BMS-only patients (mean [SD] age: 48.7 [9.5] years; 1,046 [73.2%] women). GLP-1RA initiation after BMS was associated with reduction in BMI (-7.0%) and HbA1c (-13.0%) and higher diabetes remission (78.0% vs. 61.6%). Ten-year predicted CVD risk was similar between users and nonusers before treatment initiation (0.053%) but was significantly lower among users during follow-up (0.039% vs. 0.046%). During a mean (SD) follow-up of 1.4 (0.8) years (maximum ∼10.6 years), there were 12.7 per 1,000 person months (n = 17) and 10.6 per 1,000 person months (n = 7) new cases of MACE and all-cause mortality in the BMS-only and GLP-1RA post-BMS group, respectively. No overall statistically significant association was observed between initiation of GLP-1RA after BMS and MACE/all-cause mortality. However, significant interaction was observed with time since BMS (p = 0.04), with a lower risk of MACE/all-cause mortality as the time from BMS increased. CONCLUSION:Initiation of GLP-1RAs after BMS was associated with lower BMI and HbA1c levels, higher diabetes remission, and reduced predicted CVD risk among patients with diabetes and obesity. Overall, GLP-1RA treatment after BMS did not further reduce the risk of MACE/all-cause mortality compared to BMS alone after a mean follow-up of 1.4 years. Given the observed time-dependent benefit of treatment after BMS, longer follow-up studies are needed to determine the optimal timing for initiation.
Introduction: Real-world data directly comparing the safety, tolerability, and effectiveness of semaglutide and tirzepatide in patients with obesity remain limited. This nationwide multicenter observational study compared short-term adverse events, treatment discontinuation, body weight loss (BWL), and metabolic outcomes between the two treatments. Methods: This study included 2,549 patients with obesity treated with semaglutide (n = 1,434) or tirzepatide (n = 1,115). Adverse events, including time to onset, dose at occurrence, and related discontinuation, were evaluated. Changes in BWL and metabolic parameters up to 6 months were assessed. Subgroup analyses were performed in patients with and without type 2 diabetes mellitus (T2DM). Results: At least one adverse event occurred in 50.9% in the semaglutide group and 51.0% in the tirzepatide group (p = 0.524), with gastrointestinal events the most frequently reported. Overall adverse event rates were comparable between groups; however, musculoskeletal and allergic reactions were more common in the tirzepatide group. The onset of gastrointestinal, neuropsychiatric, musculoskeletal symptoms, and hypoglycemia occurred earlier in the tirzepatide group. Discontinuation due to adverse events was similar between groups, except for pancreatic events, which were more frequent in the semaglutide group (p = 0.006). Tirzepatide was associated with greater early BWL at all time points. At 6 months, median percentage BWL was 12.6% with semaglutide and 14.4% with tirzepatide. HbA1c reductions were comparable between groups in patients with T2DM. Conclusion: In real-world clinical practice, semaglutide and tirzepatide show similar short-term tolerability and treatment persistence, although tirzepatide is associated with a higher incidence of musculoskeletal and allergic reactions and greater early BWL.
