The Journal of clinical endocrinology and metabolism最新文献

{"title":"No More Free Lunch: Challenges to Mendelian Randomization Due to Sample Selection and Complex Methods.","authors":"Tianyuan Lu, Wenmin Zhang, Fergus W Hamilton, Guillaume Butler-Laporte, Nicholas J Timpson, George Davey Smith, J Brent Richards","doi":"10.1210/clinem/dgaf305","DOIUrl":"https://doi.org/10.1210/clinem/dgaf305","url":null,"abstract":"<p><p>Mendelian randomization (MR) is increasingly used in epidemiological studies to investigate causal relationships. MR depends on 3 fundamental instrumental variable assumptions: relevance, independence, and exclusion restriction. Studies often assume that MR mitigates bias from confounding due to the random allocation of genetic variants at conception. In this perspective, using causal directed acyclic graphs, we discuss several scenarios where biases in MR analyses may arise due to the nature of the data or methods being used. These include (1) collider bias due to the nonrandom selection of participants into study populations used for conducting genome-wide association studies (GWAS), (2) indirect genetic effects arising from population-based GWAS rather than within-family studies, and (3) collider bias due to gene-environment interaction effects on the exposure in nonlinear MR analyses. We provide practical considerations for examining and reducing these biases in MR analyses.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144288155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Levothyroxine in Pregnancy: Protective Neurodevelopmental Role Beyond Cognitive Outcomes?","authors":"Freddy J K Toloza, Sangeetha Gummalla, Spyridoula Maraka","doi":"10.1210/clinem/dgaf351","DOIUrl":"https://doi.org/10.1210/clinem/dgaf351","url":null,"abstract":"","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144278142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Weight Trajectory Impacts Risk for Ten Distinct Cardiometabolic Diseases.","authors":"Alison Z Swartz, Kathryn Wood, Eric Farber-Eger, Alexander Petty, Heidi J Silver","doi":"10.1210/clinem/dgaf348","DOIUrl":"https://doi.org/10.1210/clinem/dgaf348","url":null,"abstract":"<p><strong>Context: </strong>Repetitive bouts of weight loss and regain, termed weight cycling, may exaggerate risk for cardiometabolic disease. We previously identified that weight cyclers were likely to have prescribed medications for hypertension, dyslipidemia, and diabetes - suggesting high prevalence of cardiometabolic disease.</p><p><strong>Objective: </strong>No prior study has compared relationships between longitudinal weight trajectory (weight stable, weight gainer, weight loser, or weight cycler) and commonly occurring specific cardiometabolic diseases among persons with similar high baseline BMI.</p><p><strong>Methods: </strong>Using de-identified electronic health record data from all adults treated at Vanderbilt University Medical Center between 1997 to 2020 and a landmark approach, we developed multivariate cox proportional hazards regression models to determine relationships between weight trajectory and risk for ten highly prevalent cardiometabolic diseases.</p><p><strong>Results: </strong>Compared to weight stability, weight cycling associated with almost 30% increased risk for obstructive sleep apnea (HR 1.28; 95% CI 1.15-1.42), MASLD (HR 1.28; 95% CI 1.08-1.51), and T2DM (HR 1.23; 95% CI 1.10-1.38). Weight cycling also associated with more than 50% increased risk for heart failure (HR 1.54; 95% CI 1.31-1.82), although both weight gain and weight loss also showed increased risk for HF (HR 1.29; 95% CI 1.08-1.55 and HR 1.32; 95% CI 1.10-1.58, respectively).</p><p><strong>Conclusions: </strong>The relationship between weight cycling and cardiometabolic disease risk was independent of having high baseline BMI, which was similar among weight trajectory groups. The present findings support promoting either weight stability at high BMI or weight loss if able to be maintained to prevent the incidence of a variety of cardiometabolic diseases.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144278113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediabetes subgroups, type 2 diabetes risk, and differential effects of preventive interventions.","authors":"Jeanette M Stafford, Ramon Casanova, Byron C Jaeger, Yitbarek Demesie, Brian J Wells, Michael P Bancks","doi":"10.1210/clinem/dgaf350","DOIUrl":"https://doi.org/10.1210/clinem/dgaf350","url":null,"abstract":"<p><strong>Objective: </strong>Prior studies have subclassified type 2 diabetes using statistical clustering approaches with clinical data, but few have subclassified prediabetes and assessed effects of preventive interventions. Our objective was to derive prediabetes subgroups based on clinical biomarkers and assess risk for incident diabetes and differential preventive intervention effects within the derived subgroups, with comparison to more simple modeling approaches.</p><p><strong>Methods: </strong>Baseline data for 3145 participants in the Diabetes Prevention Program trial were used to derive prediabetes subgroups using K-means clustering with data for 22 clinical biomarkers (sex-standardized). Cox proportional hazards regression was used to estimate hazard ratios (HR) for diabetes and differential intervention effects (intensive lifestyle, metformin, or placebo) by prediabetes subgroups and to compare the clustering strategy to a model with clinical variables.</p><p><strong>Results: </strong>We identified two prediabetes subgroups characterized by severe insulin resistance with severe obesity (subgroup 1, 31% of sample) and moderate insulin resistance with overweight or obesity (subgroup 2, 69%). Subgroup 1 had 58% higher risk for diabetes (HR: 1.58, 95% confidence interval: 1.31, 1.91) compared to subgroup 2. Randomization to lifestyle (compared to placebo) halved diabetes risk for both subgroups, while metformin provided greater benefit to subgroup 1 versus subgroup 2 (p for interaction <0.05). A clinical variable model discriminated diabetes risk better than the clustering strategy.</p><p><strong>Conclusion: </strong>Pathophysiologically distinct prediabetes subgroups differ in risk for diabetes and preventive benefit from metformin. These results support distinct mechanisms of diabetes susceptibility, however use of clinical prediction models to guide treatment decisions may provide adequate risk profiling.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144268457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The relationships between MASLD, extrahepatic multimorbidity and all-cause mortality in UK Biobank cohort.","authors":"Qi Feng, Chioma N Izzi-Engbeaya, Andrea D Branch, Benjamin H Mullish, Pinelopi Manousou, Mark Woodward","doi":"10.1210/clinem/dgaf342","DOIUrl":"https://doi.org/10.1210/clinem/dgaf342","url":null,"abstract":"<p><strong>Background & aims: </strong>This study aimed to estimate the impact of metabolic dysfunction-associated steatotic liver disease (MASLD), with and without multimorbidity, on all-cause mortality.</p><p><strong>Methods: </strong>We analysed data from the UK Biobank. MASLD was identified as a fatty liver index (FLI) ≥ 60 and presence of cardiometabolic risk factors. Multimorbidity was defined as ≥2 of the long-term conditions (LTCs) in a pre-specified list of 47 extrahepatic conditions. Hazard ratios (HRs) from adjusted Cox models quantified the association between MASLD, multimorbidity and all-cause mortality.</p><p><strong>Results: </strong>Of the 438,840 participants, 131,020 (29.9%) had MASLD at baseline. The participants with MASLD at baseline had a higher prevalence of multimorbidity than those without (21.3% vs. 14.4%). In addition to cardiometabolic risk factors, MASLD was strongly associated with several LTCs, particularly metabolic, cardiovascular, cancers, kidney, mental/behavioural, and respiratory diseases. During a median follow-up of 13 years, MASLD was associated with higher mortality (HR 1.16 (95%CI: 1.13, 1.19)), with stronger associations in females and in those with low LTC counts (≤3 LTCs). Each additional LTC at baseline was associated with 30% and 38% higher mortality in MASLD (HR 1.30 (1.29, 1.32)) and non-MASLD (HR 1.38 (1.37, 1.40)) populations, respectively. Among the 47 LTCs, 16 were associated with increased mortality in people with MASLD.</p><p><strong>Conclusion: </strong>Those with MASLD exhibited a higher prevalence of extrahepatic multimorbidity and a 16% higher rate of mortality than those without, underscoring the impact of liver steatosis on mortality and highlighting the need to target LTCs to improve outcomes and reduce healthcare burdens.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144268483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of GLP-1-based Therapies on Metabolic Dysfunction-Associated Steatotic Liver Disease and Metabolic Dysfunction-Associated Steatohepatitis: A Systematic Review and Meta-Analysis.","authors":"Yahao Wang, Yue Zhou, Zhihong Wang, Yunzhi Ni, Gerald J Prud'homme, Qinghua Wang","doi":"10.1210/clinem/dgaf336","DOIUrl":"https://doi.org/10.1210/clinem/dgaf336","url":null,"abstract":"<p><strong>Objective: </strong>New therapies are urgently needed for the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH). We conducted this systematic review and meta-analysis to evaluate the therapeutic effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on MASLD/MASH.</p><p><strong>Methods: </strong>We searched PubMed, Embase and Cochrane Library database to identify randomized controlled trials (RCTs) that compared GLP-1RAs with placebo or active agents with respect to the efficacy in patients with MASLD/MASH. The effects of GLP-1RAs on liver fat content (LFC) by imaging, liver histology, serum liver enzymes, and noninvasive fibrosis indexes (fibrosis-4, NFS, CK-18, procollagen III and liver stiffness) were evaluated. Mean differences (MDs) and risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using a random-effect model.</p><p><strong>Results: </strong>25 RCTs involving 2600 patients that used GLP-1RAs including liraglutide, exenatide, dulaglutide, semaglutide, tirzepatide, efinopegdutide, survodutide and retatrutide were included. Overall, GLP-1RAs treatment for a median of 24 weeks demonstrated a significant reduction in LFC by 5.21%, with the retatrutide displaying the most obvious treatment effects. GLP-1RAs treatment induced significant histological improvements in steatosis, hepatocellular ballooning and lobular inflammation, but non-significantly improved fibrosis, with the evidence for tirzepatide more robust than that for semaglutide and liraglutide. GLP-1RAs treatment significantly decreased serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyl transferase (GGT) compared with control. GLP-1RAs also significantly improved liver stiffness, with semaglutide displaying the most obvious treatment effect. No drug-related adverse effects involving the liver was observed.</p><p><strong>Conclusion: </strong>GLP-1RAs decreased liver fat deposition and improved histological steatosis, hepatocellular ballooning and lobular inflammation, without worsening of fibrosis in MASLD and MASH.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incretin Receptor Agonism, Fat-free Mass, and Cardiorespiratory Fitness: A Narrative Review.","authors":"Zhenqi Liu, Nathan R Weeldreyer, Siddhartha S Angadi","doi":"10.1210/clinem/dgaf335","DOIUrl":"https://doi.org/10.1210/clinem/dgaf335","url":null,"abstract":"<p><strong>Context: </strong>Individuals with obesity often exhibit low muscle quality and are at risk of reduced muscle mass and diminished cardiorespiratory fitness (CRF). Glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1RA) and dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist (GLP-1/GIPRA) promote significant loss in adipose tissue but are also associated with notable reductions in fat-free mass (FFM). It is not yet understood how these drugs affect CRF which is an independent predictor of all-cause and cardiovascular mortality.</p><p><strong>Evidence description: </strong>People with obesity frequently have low CRF which is defined by the Fick principle - the product of cardiac output and peripheral oxygen extraction. Cardiovascular dysfunction and reduced muscle quality, due to lipid infiltration, relatively low muscle mass, and dysfunctional microvasculature, work in concert to affect the determinants of the Fick equation and cause low CRF in this population. Weight loss interventions, including GLP-1RAs and dual GLP-1/GIPRA, may improve these measures. However, recent trials show GLP-1RAs and dual GLP-1/GIPRA therapy accelerates FFM loss. Evidence indicates that approximately 25-40% of weight loss attributed to GLP-1RAs and dual GLP-1/GIPRA comes from FFM loss, a rate far exceeding the annual age-related decline of FFM in adults. While these therapies have revolutionized obesity and glycemic management by inducing significant weight loss, reducing blood glucose levels, and demonstrating cardiovascular benefits in individuals with or without type 2 diabetes, clinical studies have failed to show improvements in CRF, a critical determinant of long-term cardiovascular health, and the long-term implications of FFM loss in these individuals remain unknown.</p><p><strong>Conclusion: </strong>GLP-1RAs and dual GLP-1/GIPRA significantly reduce body weight and adiposity, along with a substantial FFM loss but with no clear evidence of CRF enhancement. Further research is needed to elucidate the complex interplay among GLP-1 and dual GLP-1/GIP receptor agonism, FFM, direct cardiovascular measures, and determinants of CRF to optimize clinical outcomes in obesity and type 2 diabetes.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiomyopathy in patients with acromegaly - not truly a concern anymore?","authors":"Peter Wolf, Luigi Maione, Peter Kamenický, Philippe Chanson","doi":"10.1210/clinem/dgaf338","DOIUrl":"https://doi.org/10.1210/clinem/dgaf338","url":null,"abstract":"<p><p>Acromegaly is associated with increased mortality rates if not adequately treated. Cardiovascular and metabolic comorbidities are highly prevalent and have long been considered the main cause of death among patients with acromegaly. However, substantial advances in GH/IGF-I-lowering treatment, together with increased awareness and optimized management of other risk factors, have led to major improvements in mortality rates in the 2-3 past decades. Here we review the effects of chronic excessive GH/IGF-I production and the successful treatment of this condition on relevant classical cardiovascular risk factors. and on morphological and functional changes in the heart and discuss differences in reported prevalence rates over time according to different imaging methodologies used. While morphological alterations, i.e., myocardial hypertrophy as well as increased atrial and ventricular volumes, are common in patients with acromegaly, overt clinically relevant dysfunction is rare. Valvular cardiac disease and arrhythmia are also reviewed. Clinically relevant cardiomyopathy is currently less common than previously estimated. Recent epidemiological studies have shown that the risk of heart failure is comparable to that of the general population after adjusting for biochemical disease control and other risk factors.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucose Parameters, Inflammation Markers, and Gut Microbiota Changes of Gut Microbiome-Targeted Therapies in Type 2 Diabetes Mellitus: a Systematic Review and Meta-Analysis of Randomized Controlled Trials.","authors":"Xin Zhou, Wenbin Zheng, Wen Kong, Jiaoyue Zhang, Yunfei Liao, Jie Min, Tianshu Zeng","doi":"10.1210/clinem/dgaf340","DOIUrl":"https://doi.org/10.1210/clinem/dgaf340","url":null,"abstract":"<p><strong>Purpose: </strong>This meta-analysis aims to summarize the effects of gut microbiome-targeted therapies (MTTs) on glucometabolic, inflammatory factors and gut microbiota in patients with type 2 diabetes mellitus (T2DM).</p><p><strong>Methods: </strong>4 databases were searched for randomized controlled trials (RCTs) that included subjects with T2DM who received MTTs. All results were presented as standardized mean difference (SMD)/MD and 95% confidence intervals (95% CIs). In addition, subgroup analyses were performed according to region, type of MTTs, number of probiotic strains, probiotics dose, prebiotics dose, duration of MTTs, mean age, and baseline body mass index.</p><p><strong>Results: </strong>Fifty-four RCTs were included, encompassing 60 groups and 3,390 subjects. Overall, MTTs intervention decreased fasting plasma glucose (MD = -7.97 mg/dL, 95%CI =-10.82, -5.12; p ＜0.00001), 2h-postprandial blood glucose (MD = -43.30 mg/dL, 95%CI = -75.83, -10.77; p = 0.009), fasting insulin (MD = -1.73uU/ml, 95%CI = -2.63, -0.84; p = 0.0001), HbA1c (MD = -0.28%, 95%CI = -0.39, -0.17; p ＜0.00001), and Homeostatic Model Assessment of Insulin Resistance (MD =-0.53, 95%CI = -0.85, -0.20; P=0.0002). Furthermore, MTTs supplementation reduced high-sensitivity C-reactive protein, tumor necrosis factor alpha, and lipopolysaccharides. Meanwhile, the levels of Interleukin-10 were increased. Moreover, the abundance of Actinobacteria, Lactobacillus, and Lactobacillus casei subgroup increased.</p><p><strong>Conclusion: </strong>MTTs modestly improved glucometabolic parameters, reduced pro-inflammatory cytokines, and enriched beneficial microbes (e.g., Actinobacteria, Lactobacillus) in T2DM. However, heterogeneity and limited long-term data highlight the need for large-scale RCTs.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammation-associated lipidomic signatures prior to carotid artery atherosclerosis in people living with HIV.","authors":"Yingying Ding, Xiaoxiao Chen, Weiwei Shen, Hao Yin, Yunqiu Zhang, Cheng Feng, Jiayu He, Miaochen Wang, Jingjing Xia, Haijiang Lin, Na He","doi":"10.1210/clinem/dgaf331","DOIUrl":"https://doi.org/10.1210/clinem/dgaf331","url":null,"abstract":"<p><strong>Objectives: </strong>Lipid metabolism plays an important role in HIV-associated atherosclerosis. However, the interplay between lipid metabolism, uncontrolled inflammation and subclinical carotid atherosclerosis (SCA) in HIV infection remains poorly understood. This study aimed to characterize lipidome signatures that, togetherwith inflammatory patterns, may predispose HIV-positive individuals to incident SCA.</p><p><strong>Methods: </strong>A nested case-control study was conducted within the Comparative HIV and Aging Research Cohort in Taizhou, China, including 115 HIV-positive individuals with incident SCA, 112 age and sex comparable HIV-positive normal controls, and 117 HIV-negative normal controls. Untargeted lipidomic profiling and inflammatory marker assessments were performed at baseline and follow-up. 649 plasma lipid species were annotated and 20 plasma inflammatory markers were quantified.</p><p><strong>Results: </strong>Three distinct baseline lipidomic signatures were identified: one upregulated in HIV infection, one downregulated and one upregulated in HIV-associated SCA (showing a decreasing or increasing trend from HIV-negative NCs to HIV-positive NCs to SCA cases). The latter two signatures were p enriched in glycerophospholipid metabolism, particularly involving lysophospholipids (LPL) and short-chain fatty acyls (SCFA). Lipid species within each signature exhibited distinct correlation patterns with subsets of inflammatory proteins, a pattern that persisted after onset of SCA. Network analysis revealed that IL-18 was the only inflammatory protein showing divergent associations across lipidomic signatures, displaying positive correlations in the HIV-associated SCA-upregulated lipidomic signature and negative correlations in the other two.</p><p><strong>Discussion: </strong>Our findings underscore specific lipidomic-inflammatory networks that may underlie the heightened risk of atherosclerosis in HIV infection. The differential involvement of IL-18 suggests a central role of NLRP3 inflammasome activation in HIV-associated vascular inflammation. The observed alterations in LPL and SCFA metabolism warrant further mechanistic investigation as potential mediators of HIV-related atherogenesis.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}