In patients with advanced chronic kidney disease (CKD), risk factor reversals occur where obesity and elevated LDL cholesterol paradoxically associate with improved survival. This review synthesizes recent advances in understanding these obesity and lipid paradoxes, integrating insights from body composition, inflammation, and metabolism. Observational studies have shown stage-specific survival advantages of obesity, mainly in hemodialysis populations and among patients with inflammation. The lipid paradox is also largely explained by the confounding effects of inflammation, which suppresses cholesterol levels. Beyond quantitative assessment, emerging evidence emphasizes that assessments of body composition and lipid quality are stronger predictors of clinical outcomes. For severely obese patients, integrative strategies using lifestyle, nutritional therapy, and pharmacologic agents may modulate inflammation, reducing the risk of protein-energy wasting. Weight loss from GLP-1 receptor agonists or bariatric surgery may improve kidney transplant eligibility but requires careful individual assessment to balance this benefit with the risk of malnutrition. The obesity and lipid paradoxes in CKD are not merely anomalies nor statistical fallacies to be adjusted for, but manifestations of CKD's distinct metabolic milieu. Their recognition highlights the need for individualized approaches beyond conventional risk factor modification. By integrating assessment of body composition, nutrition, and inflammation, precision nephrology can provide tailored interventions that improve prognosis.

The Obesity Paradox in Chronic Total Occlusion Percutaneous Coronary Intervention: Contemporary Outcomes Across Body Mass Index Categories.

Does obesity improve the prognosis of patients with community-acquired pneumonia? Insights from the MIMIC-IV database.

Temporal trends in ICU outcomes by BMI: A retrospective propensity-score matched study.

While obesity is linked to increased Alzheimer's disease (AD) risk via inflammatory and metabolic pathways, conflicting evidence suggests a protective effect "obesity paradox." This meta-analysis investigates the association between various anthropometric measures and AD risk, focusing on age-dependent differences. We searched PubMed, Google Scholar, and Embase for studies assessing the association between body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), and AD risk. Thirty-eight studies were included, and a random-effects model was used to calculate pooled effect sizes (EF). Subgroup analyses and meta-regressions examined age-specific relationships. Underweight BMI was associated with borderline increased risk (ES: 1.28, 95% confidence interval [CI]: 1.00-1.64), and obese BMI was associated with decreased risk (ES: 0.78, 95% CI: 0.64-0.95). However, when stratified by age, overweight and obesity were protective on AD among aged ≥ 60 years (ES range: 0.81-0.90), but risk-enhancing for individuals aged < 60 years (ES range: 1.65-2.45). Weight loss increased AD risk, especially in older individuals (ES: 1.31, 95% CI: 1.08-1.58). A dose relationship between BMI and AD risk indicated increased risk at both low and high extremes, while higher BMI was protective in older adults. This meta-analysis revealed a complex, age-dependent association between obesity and AD, supporting the obesity paradox in older adults. These findings underscore the importance of age-specific considerations along with obesity management strategies for AD prevention and emphasize the need for further research to elucidate underlying mechanisms.

ObjectiveTo examine the associations between sleep quality and left ventricular hypertrophy (LVH) and their associations with haemodynamic and cardiometabolic risk factors among adults with hypertension in Pakistan.DesignA cross-sectional analytical study conducted from February to July 2025.SettingConducted in three tertiary care hospitals in Sialkot, Pakistan representing both urban and rural populations.ParticipantsA total of 405 participants aged ≥30 years, diagnosed with hypertension, were enrolled. Patients with primary sleep disorders, psychiatric illness, pregnancy or incomplete data were excluded.Outcome measuresSleep quality was assessed using the Urdu version of the Pittsburgh Sleep Quality Index (PSQI) with a cut-off ≥5. Blood pressure was measured as the average of three seated readings. LVH was determined by echocardiography. Modified Poisson regression with robust SEs was applied to estimate adjusted prevalence ratios (aPRs) for factors associated with LVH and poor sleep, accounting for clustering by hospital.ResultsLVH was present in 38.3% of participants, and 68.4% had poor sleep quality. In fully adjusted models for LVH, poor sleep quality was not independently associated with LVH (aPR 1.11; p=0.512).Independent associates of LVH included:Age (aPR=1.32; p<0.001).Systolic blood pressure (aPR=1.021 per mm Hg; p<0.001).Diastolic blood pressure (aPR=1.030 per mm Hg; p<0.001).Longer hypertension duration (aPR=1.47; p=0.002).Overweight (aPR=0.77) and obesity (aPR=0.71) were inversely associated with LVH, consistent with the obesity paradox. Poor sleep quality was independently associated with smoking status, longer hypertension duration and higher blood pressure. Sensitivity analyses treating PSQI as a continuous variable (aPR=1.033 per point) suggested a modest dose–response relationship between more severe sleep impairment and LVH.ConclusionsElevated blood pressure, longer hypertension duration and smoking were significantly associated with LVH and poor sleep quality. Sleep quality was not an independent correlate of LVH, suggesting an indirect relationship mediated through haemodynamic factors.

Non-small cell lung cancer (NSCLC) is a biologically and clinically heterogeneous disease. In addition to tumor-intrinsic characteristics, clinical outcomes from immune checkpoint inhibitors (ICIs) are influenced by a variety of host-related factors. This review aims to summarize current evidence on how body composition, metabolic comorbidities, sex, and systemic inflammation shape anti-tumor immunity and affect immunotherapy efficacy. Emerging data suggest that altered body composition, including obesity and sarcopenia, may modulate ICI outcomes, giving rise to the so-called "obesity paradox", which appears inconsistent across tumor types and may reflect disease-specific nutritional and immunological profiles. Likewise, metabolic disorders such as type 2 diabetes and dyslipidemia can promote chronic inflammation and immune exhaustion, potentially dampening ICI activity. Advances in cross-sectional imaging and molecular profiling are refining the characterization of host-tumor-immune interactions and providing novel predictive insights. Host-related determinants play an integral role in shaping response to ICIs in NSCLC. A deeper understanding of the dynamic continuum linking metabolism, body composition, systemic inflammation, and immune regulation may enable more precise patient stratification and open opportunities for personalized immunotherapy strategies.

Objectives: We aim to investigate the relationship between body weight and the risk of cardiovascular events in heart failure patients with diabetes. Methods: We therefore conducted a retrospective analysis of HF patients with T2D using the Nationwide Readmissions Database (NRD) from 2016 to 2022. Patients were stratified by BMI classes: underweight, normal weight, overweight, and obesity classes I–III. The primary outcome was in-hospital mortality. Secondary outcomes included 1-year mortality and readmission for heart failure. Results: A total of 26,199 patients with BMI data were included in the analysis. Underweight patients had the highest risk of in-hospital mortality [aOR = 1.80 (95% CI: 1.16–2.80)] and cardiogenic shock [aOR = 2.13 (95% CI: 1.26–3.59)]. In contrast, obesity classes I–III were associated with significantly lower odds of those events. One-year mortality rates did not differ significantly across BMI groups. However, obesity classes II and III were associated with a lower adjusted risk of HF readmission [aHR = 0.71 (95% CI: 0.50–0.99); aHR = 0.68 (95% CI: 0.49–0.96), respectively]. Conclusions: In patients with T2D and HF, an obesity paradox exists whereby patients with obesity have a lower risk of in-hospital mortality and cardiogenic shock. Further, obesity classes II-III are associated with a lower risk of 1-year readmission for HF.

The “obesity paradox” suggests a protective effect of obesity on certain diseases including cardiovascular and respiratory illnesses, but results remain inconsistent, largely due to reliance on body mass index (BMI) alone. To clarify this, we used Mendelian randomization (MR) to assess causal effects of multiple obesity-related anthropometric traits on key clinical outcomes. We conducted MR analyses using summary statistics from genome-wide association study to investigate the causal effects of 13 obesity-related anthropometric indicators-including BMI, basal metabolic rate (BMR), hip circumference, waist circumference (WC), body fat percentage (BFP), arm fat mass (AFM), leg fat mass (LFM), trunk fat mass (TFM), trunk fat free mass (TFFM), whole body fat mass, whole body fat free mass (WBFFM), whole body water mass (WBWM), trunk predicted mass (TPM)-on 5 major clinical outcomes: diffuse large B cell lymphoma, pancreatic cancer, pathological fracture in patient with osteoporosis, sepsis, and 28-day mortality due to sepsis. We selected these outcomes because they represent distinct but obesity-relevant disease categories, encompassing cancer, metabolic-skeletal complications, infection, and mortality risk. Sensitivity analyses, included tests for heterogeneity and horizontal pleiotropy, were performed to assess the stability of MR results. MR analyses revealed no evidence supporting the obesity paradox but demonstrated causal associations between obesity-related traits and clinical outcomes. After excluding traits with horizontal pleiotropy, results showed: BMR, TFFM, and TPM increased diffuse large B cell lymphoma risk; BMI, BMR, AFM, LFM, TFFM, WBFFM, and TPM increased pancreatic cancer risk; BMR, TFFM, WBFFM, WBWM, and TPM increased pathological fracture risk in osteoporosis; BMI, BMR, WC, BFP, AFM, LFM, TFM, whole body fat mass and WBWM increased sepsis risk; and BMI, hip circumference, WC, BFP, AFM, LFM, and TFM increased 28-day sepsis mortality risk (all P < .05). This MR study found no evidence of an “obesity paradox” for the specific outcomes evaluated. Instead, our findings demonstrated that elevated levels of obesity-related anthropometric traits are causally associated with increased risks of diffuse large B-cell lymphoma, pancreatic cancer, pathological fractures in osteoporosis, sepsis, and sepsis-related 28-day mortality. These results provide important insights into the pathogenic role of obesity and may inform future strategies for obesity-related disease prevention and risk assessment.

Midlife obesity is a known risk factor for cognitive impairment, whereas its association in late life is complex, giving rise to the concept of the 'obesity paradox.' The weight-adjusted waist index (WWI), an indicator reflecting central obesity, has recently emerged. However, evidence regarding the association between WWI and cognitive impairment in Chinese older adults remains scarce. This study explores WWI's association with cognitive decline in older adults, addressing gaps in central obesity's role in neurocognitive health. A total of 5001 older adults aged ≥65 years with normal cognition from the Chinese Longitudinal Healthy Longevity Survey were included in this longitudinal analysis, with a median follow-up duration of 4 years. A time-varying Cox proportional hazards regression model was used to evaluate the association between WWI, waist circumference (WC), body mass index (BMI) and incident cognitive impairment. Nonlinear correlations were investigated using restricted-cubic-spline curves. Subgroup analyses and sensitivity analyses were conducted to enhance the robustness of findings. The incidence of cognitive impairment across the four WWI quartile groups (Q1-Q4) was 6.7%, 7.8%, 9.3% and 13.4%, respectively. WWI was positively associated with incident cognitive impairment, whether treated as a continuous variable (hazard ratio [HR] = 1.14, 95% confidence interval [95% CI] = 1.06-1.23) or a categorised variable (Q4 vs. Q1: HR = 1.70, 95% CI = 1.29-2.24; Q3 vs. Q1: HR = 1.43, 95% CI = 1.08-1.90) in models adjusted for multiple covariates. WC showed a similar trend, while BMI demonstrated no significant association. Associations persisted across subgroups and sensitivity analyses. Elevated WWI and WC, but not BMI, were significantly associated with an increased risk of incident cognitive impairment. The findings suggested that WWI may be a more precise indicator of the association between obesity and cognitive impairment.

A comorbid hypertension was previously associated with survival advantages in patients with stroke. We aimed to explore how strong priors for the hypertension covariate affect the reverse association, as a way to test the sensitivity of reverse epidemiology findings to bias assumptions. The authors used stroke data from 2014 to 2019 (N = 177,947) and subsequently performed random sampling from a population of various sizes. The data were analyzed using Bayesian multiple logistic mixed-effects regression, which was further modelled in three scenarios: with informative (strong) priors, non-informative priors, and accounting for the interaction mechanism (age*hypertension). In addition, we perform a series of sensitivity analyses to check the robustness of the estimates to different prior choices. Both informative and non-informative priors demonstrated elevated posterior odds ratios (ORs) for hypertension in low sample fractions (n = 100–500). As the sample size increased, the ORs declined (below 1) for each subsequently larger samples. The ORs plateaued as the sample exceeded 5000 and became similar for both the modeling scenarios. Conversely, the interaction term revealed inverse patterns, increasing in effect as the sample size grew large. Thus, the reverse effect of hypertension diminishes with age. Although further modifications of prior precision revealed somewhat higher ORs for hypertension covariate, the estimates mostly overlapped. Bayesian analysis may improve the interpretation of reverse associations when data are limited; however, in large datasets, their influence diminishes. This pattern suggests that reverse associations reflect collider or selection bias rather than prior choice and that Bayesian priors alone cannot address design bias.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-30952-z.

Impact of Hemoglobin A1c on the Obesity Paradox and Survival in Patients With Non-Metastatic Renal Cell Carcinoma.

Obesity and GEP-NEN: what's new?

The ‘obesity paradox’ in patients undergoing transcatheter aortic valve implantation. A specialized narrative review

BackgroundHigher body mass index (BMI) has often been linked to a heightened risk for cognitive decline; however, emerging evidence suggests a potential “obesity paradox,” in which overweight or obese older adults may actually experience a slower rate of cognitive decline. Using a large, longitudinal cohort of older adults from 25 sites across the United States, we examined the relationship between BMI and cognition.MethodData were drawn from the National Alzheimer’s Coordinating Center (NACC) database over five annual visits. Cognition was measured by the Montreal Cognitive Assessment (MoCA). Clinically‐assessed BMI was categorized as normal, overweight, and obese. Time‐varying covariate measures included age and presence of clinically‐assessed comorbidities (i.e., diabetes, hyperlipidemia, and hypertension). To test the association between MoCA and BMI, we used linear‐mixed effects regression models with random intercepts and fixed effects for BMI, time, and their interaction with covariate measures. We performed sensitivity analyses stratified by age (55‐75, and ≥ 76).ResultIn the full sample (n =526 participants, p =2630 observations), total raw MoCA scores significantly decreased from visit 1 to visit 5 (β = ‐0.71, p<0.05). Age was negatively associated with MoCA (β = ‐0.09, p<0.5). There was no significant main effect of BMI on MoCA, however there were significant interactions between BMI categories and time. Specifically, obese (β = 0.86, p< 0.05) and overweight (β = 0.95, p <0.05) participants showed a slower rate of decline in MoCA over five visits compared to normal‐weight individuals. The same pattern of results held for participants aged 55‐75 as in the full sample. However, among those 76 years and older, being overweight or obese no longer significantly reduced the MoCA decline over the five visits. Comorbidities were not associated with MoCA in any of the models.ConclusionIn contrast to some previous research, our findings suggest a complex, and at times contradictory, relationship between weight status and MoCA score, where overweight or obesity may modestly buffer against cognitive decline based on age. Further research should explore potential age‐dependent effects, clarify casual pathways, and determine whether targeted interventions around BMI might modify late‐life cognitive trajectories.

Nutritional and inflammatory status in the obesity paradox of coronary artery disease.

Prevalence and Prognostic Differences Between Sarcopenia and Sarcopenic Obesity in Heart Failure.

Background/Objectives: The relationship between body mass index (BMI) and clinical outcomes in sepsis patients remains controversial, with some studies suggesting an "obesity paradox" and others indicating increased risks for underweight individuals. This study aims to further explore the impact of BMI on mortality and other specific sepsis outcomes. Methods: This was a retrospective cohort study of adult patients with sepsis admitted to the intensive care unit (ICU) from 1 January 2021 to 31 December 2023. Patients were divided into four groups according to BMI category. The primary outcome of this study was ICU mortality. Secondary outcomes included the development of septic shock, acute respiratory distress syndrome, 30- and 90-day mortality, ICU and hospital length of stay, and vasopressor- and/or ventilation-free days. Results: A total of 559 patients were included in the study. Among these, 51 were in the underweight group, 206 were in the normal weight group, 158 were in the overweight group, and 184 were in the obese group. The primary outcome of ICU mortality was not significantly different among all BMI groups (p-value > 0.05). Similarly, all secondary outcomes were not significantly different between the groups. Conclusions: Our findings demonstrate that BMI in sepsis patients is not associated with worse clinical outcomes. Further prospective research is warranted to confirm these findings on a larger scale.

The aim of the study was to carry out a comparative effect assessment of methotrexate (MTX), adalimumab (ADA), and tocilizumab (TOC) on the blood lipid profile in children with JIA to figure out possible metabolic consequences and risks. Materials and methods: 120 patients with JIA were enrolled in the study and later divided into 3 different therapy-based groups: ADA group (n=60), TOC group (n=30), and MTX group (n=30). All patients underwent the same clinical, laboratory and instrumental evaluation, which included the disease activity assessment by JADAS27 scale and lipid profile analysis (total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), very low density lipoprotein cholesterol (VLDL-C), triglycerides (TG), atherogenic coefficient (AC), both at disease onset and 3 months after reaching the pharmacological remission. Results: There were no statistically significant differences in TC, VLDL-C, and AC levels between the therapy groups at enrollment. However, the TOC group had higher TG and VLDL-C levels. All groups showed decreases in LDL-C and HDL-C levels, therefore suggesting a “lipid paradox”. Statistically significant differences were detected during remission: patients in the ADA group had a stable lipid profile with increasing HDL-C levels, whereas in the TOC and MTX groups a significant increase in atherogenic lipid parameters was seen (TC, LDL-C, TG, AC) together with a reduction in HDL-C levels. The relative incidence of dyslipidemia in remission was 33% in the ADA group, 97% in the TOC group, and 73% in the MTX group. Only in ADA group, 8.3% of patients showed regression of dyslipidemia. Spearman correlation analysis showed direct relations of JIA activity by JADAS27 with atherogenic lipids, confirming the inflammation influence on lipid metabolism even in remission. Conclusions: The results suggest that the use of different JIA therapy can significantly affect the blood lipid profile. TNF-α inhibitors helped to stabilize or even improve lipid profiles, while the therapy with tocilizumab and methotrexate was associated with the development of atherogenic dyslipidemia. This confirms the need for lipid profile monitoring in children with JIA

While obesity is a known risk factor for ischemic stroke, its prognostic value remains uncertain. We examined the independent and combined effects of body mass index (BMI) and waist-to-hip ratio (WHR) on early stroke outcomes across subtypes. In this prospective cohort study, 714 patients with acute ischemic stroke or TIA were enrolled over six months. BMI and WHR were assessed on admission. Stroke severity (NIHSS) and functional outcome at discharge (modified Rankin Scale, mRS) were recorded. Stroke aetiology was classified using TOAST and ESUS criteria. Multivariable regression and restricted cubic spline models were applied. A U-shaped association emerged between BMI and both stroke severity and recovery, with overweight patients (BMI 25.0-29.9 kg/m²) showing the lowest NIHSS and highest independence rate (mRS 0-1: 65%). Underweight and obese patients had significantly worse outcomes (p < 0.001). WHR was an independent predictor of higher stroke severity (β = +2.8; 95% CI: 2.1-3.5) and poor outcome (OR = 0.70; 95% CI: 0.52-0.94), and showed additive prognostic value when combined with BMI. A sex-specific interaction suggested a greater benefit from overweight in women (OR = 1.72; p = 0.02). Subtype analysis revealed a U-shaped BMI association in cardioembolic stroke (p = 0.014), but not in ESUS. BMI and WHR show distinct, nonlinear, and sex- and subtype-specific associations with stroke severity and outcome. WHR outperforms BMI and enhances prognostication when combined. These findings challenge the obesity paradox and support integrating adiposity phenotypes into individualized stroke risk models.