Improving public perceptions of obesity may be crucial for preventing the disease and enhancing its management in people with obesity (PwO). This study aimed to examine perceptions concerning obesity among PwO and the general public. In this cross-sectional qualitative study, consecutive patients visiting the obesity clinic of the University Hospitals of Brussels between December 2023 and May 2024 were invited to participate. Members of the general public (BMI < 25 kg/m²) were recruited at 3 Belgian train stations (Gent, Brussel, Jette). Participants were interviewed, and data were analysed thematically. Thirty PwO and 24 individuals of the general public were interviewed. This study revealed contrasting views on whether obesity should be classified as a disease between patients and the general public. Participants who opposed the recognition of obesity as a disease emphasized personal responsibility as the central factor and advocated for lifestyle changes as the sole form of treatment and management. In contrast, individuals recognizing obesity as a disease underscored the role of biological factors as critical contributors to its development. They emphasized the necessity of a multidisciplinary treatment approach and noted that current behavioural treatments are sometimes insufficient. Limited differences in obesity-related perceptions between patients living with obesity and the general public were noted. In both populations, perceptions of obesity as a disease varied considerably, underscoring persistent knowledge gaps, even in PwO, highlighting the need for public health strategies that emphasize the biological foundations of obesity and the importance of multidisciplinary care approaches, including pharmacotherapy, in its effective management.
Despite the high prevalence of co-occurring conditions between obesity and depression, the knowledge of the underlying mechanisms remains limited. Given the existing evidence of obesity being an inflammatory condition and the association between elevated inflammation and treatment-resistant depression, investigations to uncover immune pathways underlying the obesity-depression link will shed light on the mechanisms and therapeutic options. We investigated whether depressive symptoms and adiposity are associated with greater inflammation and with suppressed innate immune responses to an immune challenge. Immune activities and depressive symptoms using the Beck Depression Inventory (BDI) were assessed in 96 participants of a weight range (normal weight, overweight, or obesity). Percent adiposity was measured by dual-energy X-ray absorptiometry. Plasma c-reactive protein (CRP), tumor necrosis factor (TNF), interleukin (IL)-1β, and IL-6 levels were determined by immunoassay. Lipopolysaccharides (LPS)-stimulated intracellular TNF in peripheral blood monocytes was assessed by flow cytometry, which was also examined after incubation with recombinant TNF (rTNF) in 10 healthy participants of normal body mass index (BMI). Obese, but not overweight, participants showed significantly higher BDI scores (T93 = 2.70, P < 0.05) and plasma levels of CRP (T95 = 3.71, P < 0.01), but lower LPS-stimulated monocytic TNF production (T93 = 3.23, P < 0.01), than normal-weight subjects. Depressive symptoms were associated with BMI, % total and trunk fat, and plasma CRP levels (r's .22 - .35) but not with monocytic TNF production in univariate model. The association between BDI and inflammatory markers largely diminished after adjusting for demographic variables and blood pressure, and the association with obesity/adiposity disappeared in the final multivariate model. Plasma TNF levels and monocytic TNF production were negatively associated (r = -0.37, P < 0.05) in univariate but not in multivariate models after controlling for covariates. BMI (std = -0.33), %total fat (std = -0.54) and %trunk fat (std = -0.57) remained significant predictors for monocyte TNF production even after controlling for demographic and plasma inflammatory marker levels (All P's < 0.01). Prolonged (24-hour) exposure of blood monocytes to rTNF in vitro suppressed LPS-stimulated monocytic TNF production in a dose-dependent manner, whereas acute rTNF pre-treatment potentiated TNF production. Our findings provide the evidence that greater adiposity is associated with depressive symptoms and that obese individuals even without clinical depression experience elevated depressive symptoms. Whether immunologic dysregulation underlies this depressive mood-adiposity association is inconclusive despite greater CRP and lower monocyte reactivity among the obese, but low-grade inflammation in obesity may contribute to impaired innate immune responses to immunological challenge. Additional mechanistic investigations of obesity-related immune dysregulation underlying mood disorders would inform effective therapeutics.
Objective This study aims to analyze rates of postpartum hemorrhage according to body mass index (BMI) and to investigate relative risks for postpartum hemorrhage based on body mass index. Study Design We conducted a retrospective chart review of all deliveries occurring in 2022 at two large urban hospitals in Indianapolis, Indiana, resulting in a cohort of 5686 patients. After excluding patients for missing data, a total of 4493 patients were included in the final analysis. Patients were categorized according to the CDC BMI definitions. We analyzed rates of postpartum hemorrhage according to patient variables. Results The rates of postpartum hemorrhage for patients with BMI categorized as healthy weight, overweight, Class 1 obesity, Class 2 obesity, and Class 3 obesity were 16.3%, 19.6%, 23.0%, 21.3%, and 27.7%, respectively (p<0.0001). Relative risk for postpartum hemorrhage by BMI categories was investigated using logistic regression analysis, where patients in the healthy weight cohort (BMI 18- <25) were used as the reference for risk of postpartum hemorrhage. We found that patients with Class 3 obesity had an increased risk of postpartum hemorrhage by 57% after adjusting for mode of delivery and race (aRR 1.57, 95% CI 1.20-2.04). Despite increased relative risk in all categories, we found no statistical significance for patients with BMI in the overweight category (aRR 1.19, 95% CI 0.92-1.54) or the Class 2 obesity category (aRR 1.24, 95% CI 0.05-1.63). Conclusion This study shows a significantly increased risk of postpartum hemorrhage among obese patients, particularly those with class 3 obesity. Notably, we did not observe a dose-dependent effect of BMI on rates of postpartum hemorrhage as there was in fact a marginal decrease in rates of postpartum hemorrhage when comparing Class 1 and Class 2 obesity. This study supports risk-based initiatives to address increasing postpartum hemorrhage rates in the United States.
This study aimed to investigate the associations between visceral obesity indices and the risk of mild cognitive impairment (MCI) in patients with diabetes and to identify the most valuable visceral obesity index to develop a risk assessment nomogram. We explored the relationship between visceral obesity indices and MCI risk in patients with diabetes and developed a nomogram utilising a cohort of 1080 patients from Nanjing Drum Tower Hospital. MCI was diagnosed according to the criteria recommended by the National Institute on Aging-Alzheimer's Association Workgroup. Logistic regression models were used to identify factors independently associated with MCI in the cohort. Furthermore, the nomogram was externally validated by a multicenter retrospective cohort (Cohort 2) and a prospective cohort with a follow-up period of up to 10 years (Cohort 3). We identified a positive but non-linear dose-response relationship between visceral obesity indices and the risk of MCI in patients with diabetes. Compared with a body shape index (ABSI), visceral adiposity index (VAI), lipid accumulation product (LAP) and Chinese visceral adiposity index (CVAI), body roundness index (BRI) exhibited superior discriminative ability (AUC: 0.734, 95% CI: 0.703-0.764). The nomogram constructed from BRI, age, education and haemoglobin A1c (HbA1c) achieved an optimal AUC of 0.804 (95% CI: 0.777-0.830) in the internal validation cohort. The model exhibited consistent performance across external validations, yielding a discriminative AUC of 0.756 (95% CI: 0.722-0.790) in Cohort 2 and a 10-year predictive AUC of 0.762 (95% CI: 0.727-0.797) in Cohort 3. Higher visceral obesity indices were associated with an increased risk of MCI in patients with diabetes. Assessment of visceral obesity may help identify patients with diabetes who are at a high risk of MCI.
The global rise in obesity, a major driver of metabolic diseases, has prompted scrutiny of distinct obesity phenotypes. While overall obesity is concerning, abdominal obesity demonstrates a stronger association with metabolic dysfunction, type 2 diabetes (DM2), and cardiovascular disease (CVD). This review examines the risk of DM2, CVD, and mortality in adults with a metabolically healthy abdominal obese phenotype. A systematic search of PubMed/MEDLINE, Web of Science, Cochrane Library, and ProQuest was conducted on April 7, 2025, to identify prospective cohort studies in adults. Eligible studies compared MHAO individuals to metabolically healthy, non-abdominally obese (MHNAO) controls, focusing on outcomes including incident T2DM, fatal and non-fatal CVD events, and all-cause mortality. Pooled estimates were calculated using random-effects meta-analysis, and heterogeneity was assessed using the I² statistic. Six prospective cohort studies (n = 98,329) were included. Metabolically unhealthy individuals, regardless of abdominal obesity status, had significantly increased risks of T2DM (RR 9.00, 95% CI 7.51-10.50 for MUHAO; RR 5.03, 95% CI 4.11-5.94 for MUHNAO), CVD, and all-cause mortality (HR 1.67, 95% CI 1.42-1.93 for MUHAO; HR 1.58, 95% CI 1.36-1.79 for MUHNAO). In contrast, MHAO individuals did not show significantly elevated risks of T2DM (RR 2.44, 95% CI 0.95-3.94), CVD, or all-cause mortality (HR 1.07, 95% CI 0.88-1.27) compared to MHNAO controls. Substantial heterogeneity (I² > 50%) was observed, partly explained by differences in outcome definitions and metabolic classifications. While metabolically unhealthy phenotypes are strongly associated with adverse health outcomes, individuals with MHAO appear to have risk profiles comparable to their metabolically healthy, non-abdominally obese counterparts. Nevertheless, abdominal adiposity and metabolic status remain critical determinants of long-term health, and the MHAO phenotype may not be entirely benign. Trial Registration: PROSPERO (CRD42019111056).
Metabolic dysfunction-associated steatotic liver disease (MASLD) and its more severe version, metabolic dysfunction-associated steatohepatitis (MASH), are associated with obesity, dyslipidemia, diabetes, and atherothrombosis for reasons that are not well understood. Protease-activated receptor 2 (PAR2), a receptor activated by coagulation proteases that are dysregulated in inflammatory and fibrotic diseases, is emerging as a new drug target for MASH. We conducted a cross-sectional study of liver specimens from patients who were obese vs. non-obese (n = 105) with the diagnosis of MASLD or MASH to examine the relationship between hepatic PAR2 expression, MASLD/MASH, and obesity. To address the direct contribution of hepatocyte PAR2 to progression of MASLD and obesity, we fed hepatocyte-specific PAR2 knockout mice, whole-body PAR2-deficient mice, and control floxed wild-type mice high-fat diet and conducted metabolic, biochemical, and molecular analyses. We discovered that expression of PAR2 is increased by five-to sevenfold (p = 0.002) in the livers of patients with obesity with MASLD and MASH. Hepatocyte-specific deletion of PAR2 caused reductions in body weight, liver fibrosis, and significantly lowered triglycerides and cholesterol levels in plasma and livers of mice fed high-fat diet. Global or hepatocyte-specific deletion of PAR2 resulted in significant improvements in fatty acid metabolic and reverse cholesterol transport pathways in liver. Mechanistic studies revealed that coagulation factor Xa activates a PAR2-cJun pathway that represses the HNF4α pioneer transcription factor which has global adverse effects on liver metabolism. OA-235i, a PAR2 inhibitor, enhanced HNF4α expression in livers and afforded a significant 15% reduction in weight gain (p <0.0001), and improvements in systemic and liver lipid and cholesterol levels in obese mouse models. These data provide support that targeting hepatic PAR2 may potentially provide broad liver and cardiometabolic benefits to patients with MASLD and MASH. Dyslipidemia and heightened coagulation are closely linked with poor cardiometabolic outcomes in patients with fatty liver disease, but the connection with progression of MASLD to steatohepatitis (MASH) is complex and not well understood. In this study, the authors now link the factor Xa coagulation protease receptor PAR2 with obesity and dyslipidemia and showed that hepatic PAR2 expression is significantly elevated in patients who are overweight or obese with MASLD and MASH compared with non-obese controls. A liver-homing PAR2 pepducin, OA-235i, conferred significantly lower body weight gain with major improvements in liver histology, fibrosis, and cholesterol and triglyceride levels in mice with MASLD. The translational studies presented here support additional investigation to determine whether a PAR2 inhibitor represents a new therapeutic strategy to treat patients with severe metabolic diseases such as MASLD and MASH.
To investigate the link between serum 25-hydroxyvitamin D [25(OH)D] and obesity in postmenopausal women, and to evaluate the potential mediating effect of the atherogenic index of plasma (AIP). In this cross-sectional analysis, data from 3386 postmenopausal women were extracted from the National Health and Nutrition Examination Survey (2011-2018). Participants were stratified by vitamin D status: deficient (< 50 nmol/L), insufficient (50-75 nmol/L), and sufficient (≥ 75 nmol/L). Adjusted weighted regression models assessed associations with body mass index (BMI) and obesity (BMI ≥ 30 kg/m2), while mediation analysis quantified the role of AIP. After comprehensive covariate adjustment, a significant inverse relationship was observed between serum 25(OH)D and BMI (β = -2.36, 95% CI: -3.16, -1.55). Vitamin D deficient women exhibited a mean BMI increase of 1.98 units (95% CI: 0.96, 3.00) and an elevated odds of obesity (OR = 1.81, 95% CI: 1.30, 2.50) relative to the sufficient group. These findings were robust across demographic and clinical subgroups. Mediation analysis indicated AIP accounted for 9.53% of the association with BMI and 9.40% with obesity (both p < 0.001). This study demonstrates a significant inverse association between vitamin D status and obesity in postmenopausal women, with lipid metabolism, as reflected by AIP, partially mediating this relationship. Further longitudinal research is required to establish causality.
Childhood overweight and obesity are growing public health concerns worldwide. Among dietary elements, dietary phytochemicals have been suggested to play a role in weight management. We aim to investigate the association between dietary phytochemical index (DPI) and the risk of overweight and obesity in primary school girls in Kerman City, Iran. Three hundred and thirty primary school girls between the ages of 6 and 12 entered this study. We used standard protocols for measuring anthropometric indices. Obesity and overweight were defined according to BMI-for-age Z-Score (BAZ) based on World Health Organization Z-Scores charts for girls aged 5-19 years old. The dietary phytochemical index was calculated using McCarty method. We assessed sociodemographic status and physical activity using valid questionnaires. Participants in higher tertile of DPI have significantly higher intakes of energy (p = 0.003), energy from phytochemical food groups (p < 0.001), fiber (p < 0.001), whole grains (p < 0.001), fruits (p < 0.001), vegetables (p < 0.001), and nuts and seeds (p < 0.001). A higher intake of supplements was associated with a higher DPI (8.5% vs. 3.9%; p = 0.034). Participants in the higher tertile compare with a lower tertile of DPI have significantly higher BAZ (0.47 ± 0.12 vs. 0.01 ± 0.12; p = 0.023). However, a significant direct association was revealed between DPI and overweight (OR 2.05; CI 1.02-4.15, p = 0.037). In conclusion, our findings suggest that a diet high in phytochemicals might be associated with a higher prevalence of overweight in children, but not obesity.
Adolescents with overweight/obesity have an elevated risk of mental health and behavioral difficulties. Exercise has been shown to impart psychological benefits to these individuals; however, whether the effects of moderate-to-vigorous physical activity (MVPA) delivery differ between weekdays and weekends is limited. Therefore, this study aimed to examine the effects of weekday and weekend MVPA at age 14 on internalizing and externalizing problems at age 17 among adolescents with overweight/obesity. We analyzed data from two assessment waves of the UK Millennium Cohort Study (MSC): MCS6 (2015-2016; age ∼14) and MCS7 (2018-2019; age ∼17). Data were restricted to adolescents classified as overweight/obesity at MCS6 using the UK90 thresholds. Weekday and weekend MVPA were measured at age 14 using the wrist-worn GENEActiv accelerometer, including one pre-specified weekday and one weekend day. Outcomes at age 17 were parent-reported Strengths and Difficulties Questionnaire (SDQ) internalizing (emotional + peer problems) and externalizing (conduct + hyperactivity/inattention) composites. We estimated average treatment effects (ATEs) and conditional average treatment effect (CATEs, heterogeneous effects) using a causal forest framework (EconML) and adjusted for pre-exposure covariates (age, sex, body mass index, ethnicity, cognitive decision-making, household income, parental education, and parental mental health). Missing data were treated via K-Nearest Neighbors imputation. The analytic sample included 1,238 adolescents (mean age 14.25 years). Mean MVPA was higher on weekdays than weekends (135.74 ± 62.08 vs 113.80 ± 64.37 min/day). Covariate-adjusted average treatment effects (ATEs; per 1 min/day MVPA) were small and not statistically significant for internalizing or externalizing problems. Weekday MVPA ATEs were -0.0025 (95% CI -0.0062 to 0.0012) for internalizing and 0.0003 (-0.0027 to 0.0033) for externalizing; weekend MVPA ATEs were -0.0008 (-0.0051 to 0.0035) and 0.0005 (-0.0026 to 0.0037), respectively. Heterogeneity was evident only for weekday MVPA effects on internalizing (22.98% with significant individual effects), with height as the strongest moderator (β = 0.0002; p < 0.001; R² = 0.519) and more negative CATEs among shorter adolescents (Q1 -0.004994 vs Q4 -0.001903; ANOVA F = 106.741, p < 0.001). In adolescents with overweight/obesity, estimated average effects of weekday and weekend MVPA at the age of 14 on parent-reported internalizing and externalizing problems at age 17 were close to zero under a selection-on-observables framework. Any potential benefits may be subgroup-specific and context-dependent; the observed weekday-specific heterogeneity warrants replication with more reliable exposure measurement and a richer set of contextual covariates.
The aim was to identify neurodevelopmental diagnoses and problems, and the extent of their overlap in children undergoing obesity treatment. Totally 139 children (72 girls; mean age 12.7 years, mean BMI SDS 3.1) were recruited from three obesity clinics in Sweden. Motor, executive, perception, memory, language, learning, social and emotional/behavioural functioning were assessed with an age-normed questionnaire. Scores ≥ the 90th percentile were considered indicative of problems with probable clinical relevance in each domain. Neurodevelopmental diagnoses were subsequently collected from the patients' records. The proportion of children exceeding the clinical threshold in each domain was compared with the expected population frequency (10%) and between participants with and without neurodevelopmental disorders. The proportion exceeding the 90th percentile was significantly higher than the expected 10% in all domains: ranging from 33.6% (memory functioning) to 54.0% (emotional/behavioral functioning) (p < 0.001). Neurodevelopmental disorders were diagnosed in 52.5% (73/139). Diagnosed children had higher rates and greater overlap of neurodevelopmental problems than children without diagnoses (p < 0.001). Recognizing neurodevelopmental problems in children with obesity may improve understanding of their needs in obesity treatment settings.
Sex-specific differences in left ventricular (LV) geometry are poorly characterized across the obesity severity spectrum in real-world echocardiographic cohorts, and standard LVMI cut-offs derived from male or mixed-sex populations may systematically underclassify LVH in women. Routine transthoracic echocardiography was performed in 205 adults with overweight or obesity (BMI ≥ 25 kg/m2). LV geometry was classified into four mutually exclusive patterns: normal geometry, concentric remodeling (CR), concentric hypertrophy (CH), and eccentric hypertrophy (EH) using sex-specific LVMI thresholds (>95 g/m2 females; >115 g/m2 males) and a relative wall thickness (RWT) cut-off of 0.42. Binary logistic regression evaluated sex as an independent predictor of LV geometry outcomes, adjusting for age and obesity class. Despite higher BMI in females (35.1 vs. 29.7 kg/m2; p < 0.001), mean LVMI was paradoxically lower (87.0 vs. 93.0 g/m2; p = 0.042), yet female sex independently predicted LVH by LVMI (OR 2.11, 95% CI 1.01-4.41; p = 0.047), a finding visible only with sex-specific thresholds. Overall concentric burden was similar (CR + CH: 47.6% vs. 46.9%), but pattern distribution differed: females more often showed CH (17.7% vs. 11.1%) and EH (15.3% vs. 7.4%), while males more frequently had normal geometry (42.0%) or CR (35.8%). The divergence was greatest in the overweight subgroup: CH was nearly threefold higher in females (34.8% vs. 12.8%), and RWT was significantly greater (0.470 vs. 0.385; p = 0.020). Female sex independently predicts LVH by LVMI despite lower mean LVMI, a paradox visible only when sex-specific echocardiographic thresholds are applied. Females and males carry similar overall concentric burdens but follow divergent geometric remodeling paths, a difference detectable at the overweight threshold. These findings underscore the necessity of sex-specific LVMI reference values in echocardiographic practice.
Despite the known association between abdominal obesity (AO) and vitamin D deficiency, it remains unclear whether this combination is associated with higher mortality risk. We investigated whether the coexistence of AO and vitamin D deficiency elevates the risk of death. Five thousand, five hundred twenty participants from the ELSA Study, aged ≥ 50 years, were followed for 6 years. AO was defined by waist circumference (> 102 cm for men and > 88 cm for women). Vitamin D levels, measured via serum 25-hydroxyvitamin D [25(OH)D] concentrations, were categorised as sufficient (≥ 50 nmol/L), insufficient (30-50 nmol/L), and deficient (< 30 nmol/L). At baseline, participants were classified according to AO (non-abdominal obesity [NAO] and AO) and 25(OH)D status (sufficiency [VDS], insufficiency [VDI], and deficiency [VDD]), creating six groups: NAO/VDS, NAO/VDI, NAO/VDD, AO/VDS, AO/VDI, and AO/VDD. Cox regression models adjusted for sociodemographic, behavioural, and clinical characteristics estimated mortality risk. The NAO/VDI and NAO/VDD groups were associated with a 91% (HR = 1.91; 95% CI: 1.37-2.66) and 81% higher risk of death (HR = 1.81; 95% CI: 1.25-2.62), respectively. The AO/VDS and AO/VDI groups had a 47% (HR = 1.47; 95% CI: 1.02-2.14) and 50% higher mortality risk (HR = 1.50; 95% CI: 1.01-2.23), respectively, compared to the NAO/VDS group. The highest mortality risk was observed in the AO/VDD group (HR = 2.23; 95% CI: 1.50-3.33). AO combined with 25(OH)D deficiency increases mortality risk in older adults. Early identification and management of these conditions could reduce this risk.
This cross-sectional study explored how time-restricted eating (TRE) interacts with metabolic health and obesity (MH&O) in relation to biological age indices of different organs. Data from the National Health and Nutrition Examination Survey (2003-2018) were analyzed, including 4890 participants. TRE strategies were assessed based on eating frequency and meal timing. Indices of organ-specific biological age (heart, kidney, liver, overall), frailty index, life's essential 8, and cardiometabolic index were evaluated. Metabolic dysfunction and obesity were associated with elevated indices of organ-specific biological age and impaired cardiovascular health, with MU status related to more rapid advancement of cardiovascular biological age indices. Excessively long or short fasting durations were associated with a decline in indices of liver metabolic health and worsened cardiovascular risk markers. Moderate eating frequencies and fasting durations were associated with lower biological age indices and better health metrics across subgroups. The association between better cardiovascular health and healthy metabolism was more pronounced in individuals who ate breakfast on time. This study underscores the independent relationship of MU&O with advancement in indices of organ-specific biological age and impaired cardiovascular health metrics. It also highlights the potential role of personalized TRE in relation to modulated biological age indices across various MH&O statuses.
Endoscopic bariatric therapies, including intragastric balloons (IGBs) are effective minimally invasive options for obesity management, particularly for patients who are not candidates for bariatric surgery. This study aimed to compare the safety profiles, weight loss outcomes, and tolerability of three fluid-filled IGB systems used in routine clinical practice. We conducted a retrospective cohort study of adults who underwent intragastric balloon placement at a single private bariatric center between January 2023 and January 2025. Data were derived from a prospectively maintained clinical database. Patients received one of three fluid-filled balloons: Allurion, Medsil, or Spatz3. Baseline demographic and anthropometric characteristics, weight loss outcomes, premature balloon removal, and readmission rates were assessed through completion of treatment. Comparative analyses across balloon types were performed using appropriate parametric and nonparametric statistical tests. A total of 113 patients were included (mean age 34.9 ± 9.3 years; 91.2% female). Mean baseline body mass index (BMI) was 40.0 ± 7.9 kg/m2. Balloon distribution was Allurion (n = 13), Medsil (n = 40), and Spatz3 (n = 60). Overall mean absolute weight loss was 14.0 ± 8.3 kg, corresponding to a mean BMI reduction of 5.0 ± 3.0 kg/m2. Mean percentage total body weight loss was highest in the Spatz3 group (13.1 ± 7.3%), followed by Medsil (12.0 ± 6.2%) and Allurion (9.8 ± 3.9%); however, differences were not statistically significant (P = .33). Premature balloon removal due to intolerance occurred in 10.6% of patients, with no significant differences between balloon types. No major complications were observed. All three fluid-filled intragastric balloons demonstrated meaningful weight loss with acceptable safety and tolerability profiles. While the Spatz3 balloon achieved numerically greater weight loss, outcomes were comparable across devices without major adverse events. These findings support the role of IGBs as effective endoscopic bariatric therapies within a comprehensive obesity management framework.
We compared health care spending and utilization associated with semaglutide relative to bariatric surgery in patients with obesity and type 2 diabetes (T2D). Using MarketScan insurance claims of patients with BMI ≥ 35 and T2D from 2016 to 2021, we examined associations between choice of semaglutide, sleeve gastrectomy, or gastric bypass; 3-year health care spending (out-of-pocket [OOP] and total); and clinical outcomes (ED visits, hospital admissions, and major adverse cardiovascular events [MACE]). Analyses were adjusted using generalized linear models, inverse probability weighting, and instrumental variables. Among 6748 patients (2797 semaglutide, 2300 sleeve gastrectomy, 1651 gastric bypass), bariatric surgery patients had higher BMI and more comorbidities. In IPTW-adjusted analysis, semaglutide was associated with the highest 3-year OOP costs ($7752 vs. $5980 [sleeve gastrectomy] vs. $6591 [gastric bypass], p < 0.001), but total spending was not statistically different across the groups. Relative to semaglutide, the gastric bypass group showed higher observed ED visits (hazard ratio relative to semaglutide [95% CI]: 1.36 [1.28-1.45]) and inpatient admissions (1.25 [1.13-1.37]) and fewer MACE (0.71 [0.59-0.88]). Sleeve gastrectomy was associated with fewer long-term admissions (0.79 [0.72-0.86]) and MACE (0.79 [0.66-0.93]). For patients with T2D and obesity, compared with semaglutide, bariatric surgery is associated with lower OOP spending and similar total spending at 3 years, as well as lower long-term MACE rates.
Intermittent fasting (IF) is a popular dietary strategy for the management of obesity and reducing visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). However, the comparative efficacy of different IF modalities remains uncertain. To evaluate the efficacy of IF interventions for reducing VAT and SAT in adults with overweight and obesity. PubMed, Web of Science, and Scopus were searched from inception to July 2025 using key words related to fasting protocols and adipose tissue. Eligible studies were randomized trials of IF, including time-restricted eating (TRE), alternate-day fasting (ADF), or the 5:2 diet compared with controls (CON) or continuous caloric restriction (CR). Outcomes included changes in VAT and/or SAT in individuals with body mass index (BMI) ≥25 kg/m2. Two independent reviewers extracted data, with disagreements resolved by consensus. Twenty-four studies (n = 1930; ages 22-69 years; BMI : 27-40 kg/m2) were included, with 24 contributing to VAT and 8 to SAT analyses. Compared with CON, the 5:2 diet (standardized mean difference [SMD]: -0.54) and TRE (SMD: -0.44) led to greater reductions in VAT, whereas neither ADF nor CR had significantly larger effects. Compared with CR, TRE demonstrated a small reduction in VAT (SMD: -0.21); however, the difference was not statistically significant. Compared with CON, the 5:2 diet (SMD: -0.45) and TRE (SMD: -0.37) led to larger reductions in SAT, but ADF and CR did not lead to differential effects. No IF modality demonstrated superiority over CR for SAT. Compared with CON, specific IF modalities-particularly the 5:2 diet and TRE-produce greater reductions in VAT and SAT. However, advantages over CR are limited, with only TRE approaching greater VAT reduction and no IF modality outperforming CR for SAT. IF may serve as an alternative to CR within a broader lifestyle approach, with adherence likely driving effectiveness. PROSPERO registration no. CRD420251145598.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a progressive condition linked to obesity and insulin resistance, potentially leading to cirrhosis. While lifestyle intervention is a primary treatment, the molecular mechanisms driving the regression of advanced fibrosis remain poorly understood. We report a man in his 30 s with severe obesity (BMI 35.2 kg/m2) and advanced fibrosis (liver stiffness measurement [LSM] 18 kPa) who underwent a 12-month caloric restriction and resistance training program. He achieved 33.8% weight loss while preserving skeletal muscle, resulting in normalized liver enzymes and an 80.6% reduction in LSM. Comparative serum proteomic analysis revealed that the "Neutrophil extracellular traps (NETs) formation" pathway was the most significantly upregulated, contrasting with downregulated metabolic pathways. Detailed mapping confirmed increased expression of NETosis-essential proteins, including peptidylarginine deiminase 4 (PAD4), neutrophil elastase (NE), myeloperoxidase (MPO), and citrullinated histone H3 (citH3), alongside upstream signaling such as ROS, Akt/mTOR, and NADPH oxidase components. This case demonstrates that intensive lifestyle intervention can induce rapid regression of advanced fibrosis in MASLD. The transition from metabolic stress to NETosis activation indicates that neutrophil-mediated immune regulation may be a key driver in the systemic and hepatic remodeling process.
Combination therapy, including a renin-angiotensin system inhibitor (RASi) and a thiazide diuretic (TZD) or a calcium channel blocker (CCB), is the first-line approach in hypertension management and modulates circulating markers of the Renin-Angiotensin-Aldosterone System (RAAS). Excess adiposity may induce renin-aldosterone axis dysregulation and contribute to blood pressure variability and treatment resistance. This study aimed to evaluate the association between the renin-to-aldosterone ratio (RAR) and ambulatory blood pressure monitoring (ABPM) in treated hypertensive patients with central overweight (OW) or obesity (OB). In a cross-sectional design, 97 adults with essential hypertension and OW/OB on stable RASi + TZD and/or CCB therapy were matched with 97 normal-weight hypertensive controls. All participants underwent 24-hour ABPM and orthostatic direct renin concentration (DRC) and plasma aldosterone concentration (PAC) measurements. RAR was calculated as the ratio between DRC and PAC. For the analyses values were normalized using natural logarithm (Ln). LnRAR and LnDRC were inversely associated with 24-hour, daytime, and night-time ABP levels in controls, but not in OW/OB patients. However, higher LnRAR and LnDRC values were linked to greater odds of achieving ABP control in both OW/OB and normal-weight for 24h [LnRAR OR 1.74 (1.25-2.42), p=0.001 in OW/OB], daytime, and night-time periods, whereas LnPAC showed no significant associations. Two-way ANOVA confirmed that patients with controlled ABP had higher median LnRAR and LnDRC values than those with uncontrolled ABP, regardless of weight status (p for interaction >0.05). RAR, primarily driven by higher DRC levels and likely linked to a pharmacologic response to RAS inhibition, shows a mechanism-based association with ABP control in treated hypertension, regardless of the presence of visceral obesity.
Combined dyslipidemia of overweight/obesity (CDO) is prevalent in youth and is associated with an increased risk of early cardiovascular disease. We sought to determine the impact and safety of statin therapy for CDO in adolescents. A double-blind, randomized trial was performed across 18 North American sites. Participants aged 10 to 19 years with body mass index ≥85th %ile and CDO defined as non-high-density lipoprotein cholesterol (HDL-C) ≥120 mg/dL (3.10 mmol/L) and either low HDL-C or high triglyceride:HDL-C ratio were randomized centrally to receive either pitavastatin calcium 4 mg/d or placebo for 2 years. The primary outcome was change in carotid-femoral pulse wave velocity (PWV), assessed at baseline, 6, 12, 18, and 24 months. Secondary outcomes included safety and lipid measures. The intention-to-treat analysis included 59 participants (33 males) who received pitavastatin calcium and 60 who received placebo (32 males), enrolled from June 2018 to April 2021. There were no significant changes or trends for PWV in either group. Compared with placebo, at 24 months, pitavastatin was associated with significantly reduced low-density lipoprotein cholesterol (from 134 ± 23 mg/dL [3.47 ± 0.60 mmol/L] to 105 ± 25 mg/dL [2.72 ± 0.65] pitavastatin vs 130 ± 25 mg/dL [3.37 ± 0.65] to 126 ± 27 mg/dL [3.26 ± 0.70] placebo; P < .001). There was 1 serious adverse event (placebo), and no significant differences in liver enzymes, muscle toxicity, glucose homeostasis, or linear growth. Over 2 years, treatment with pitavastatin calcium of CDO for adolescents resulted in no changes in vascular measures. Statin therapy safely lowered atherogenic lipid particles, potentially reducing cardiovascular risk.
The burden of cardiometabolic diseases (CMDs) is rising in people with HIV (PWH). While extensive data exist on CMD prevalence in PWH receiving antiretroviral therapy (ART), comprehensive data on ART-naïve PWH are scarce. We aimed to estimate the global prevalence of hypertension, diabetes, obesity and dyslipidaemia among ART-naïve PWH and compare estimates with those on ART and HIV-negative populations. This systematic review and meta-analysis included a search of PubMed-MEDLINE, CINAHL, SCOPUS, Academic Search Premier, Africa-Wide Information and Africa-Journals Online for original articles published up to June 2024. Cross-sectional, cohort and case-control studies providing baseline data on CMD prevalence were included. Studies had to include ART-naïve PWH aged ≥15 years. Two independent reviewers conducted studies screening, data extraction and methodological quality assessment. A random-effects meta-analysis with double arc-sine transformation was used for prevalence estimates. The study was registered with PROSPERO (CRD42021226001). We included 184 studies published between 2000 and 2024, involving a total of 424 629 participants. The global pooled prevalence among ART-naïve PWH was 14.2% (95% CI: 12.4-16.1) for hypertension, 3.6% (2.9-4.3) for diabetes, 11.5% (10.3-12.9) for body mass index-based obesity, 18.3% (12.7-24.6) for waist circumference-based obesity, 14.8% (12.1-17.8) for elevated total cholesterol, 17.6% (11.3-24.8) for elevated low-density lipoprotein cholesterol, 22.9% (19.3-26.7) for elevated triglycerides and 54.6% (48.2-61.0) for low high-density lipoprotein cholesterol, all with high heterogeneity. Significant regional variations in the prevalence of diabetes, obesity and dyslipidaemia were observed according to UNAIDS regions. We found a notable prevalence of CMDs in ART-naïve PWH, with significant regional variations in the prevalence of diabetes, obesity and dyslipidaemia. This highlights the need for targeted interventions and early screening to address the growing CMD burden among PWH. ART-naïve PWH face a considerable CMD burden, emphasizing the importance of early detection and management. Regional differences in CMD prevalence call for tailored public health strategies and integration of CMD prevention into HIV care protocols.