Search Results (1,155)

Background: Non-nutritive sweeteners (NNS) are chemical substances developed by the food industry to reduce sugar and calories while preserving sweetness. Epidemiological studies have indicated a potential increased risk of certain cancers, including breast cancer (BC), associated with NNS consumption. However, the evidence has exclusively relied on self-reported dietary information rather than objective measurements of NNSs. We examined the association of urinary concentrations of NNS with BC risk in women from the large Moli-sani Study. Methods: Using a case-cohort design, a sample of 988 middle-aged women (mean age 55 ± 12 y) was randomly selected as a sub-cohort and compared to 272 women with incident BC (38 premenopausal and 234 postmenopausal). A total of 6 commonly used NNSs (i.e., aspartame, acesulfame, saccharin, sucralose, cyclamate, and steviol glycosides) were measured through liquid chromatography–mass spectrometry in spot urine samples (creatinine-adjusted concentrations; µg/mg) collected at baseline (2005–2010). The multivariable hazard ratios (HRs) were estimated using weighted Cox regression models for the case-cohort design, with each NNS modelled as a binary variable (i.e., presence vs. absence). The sum of these values produced a total urinary NNS score, which could range from 0 to 6, and was further categorised as low (0–1) or high (2–5). Results: The predominant NNS detected in urine was saccharin (E954), contributing to 77% of total NNSs, followed by steviol glycosides (E960;11%). In multivariable-adjusted Cox analyses, neither individual NNSs nor total NNS urinary concentrations were associated with overall BC risk (HR = 1.09; 95% CI 0.80–1.48 for high vs. low). However, the presence of sucralose (E955) was directly linked to premenopausal BC (HR = 5.90; 95% CI 1.44–24.20; p = 0.014), although this estimate was based on only 38 cases and was imprecise. Conclusions: Urinary NNS concentrations were not associated with overall BC risk. The observed association between urinary sucralose and premenopausal BC should be considered exploratory and hypothesis-generating and requires independent replication. Full article

Ash dieback, together with altered hydrological conditions and limited natural regeneration, threatens narrow-leaved ash (Fraxinus angustifolia Vahl) forests in Croatian floodplains. This study evaluated whether individual-tree attributes and stand structure were associated with crown damage and short-term radial-growth resilience. Ten stands in the middle Sava River floodplain were sampled using 41 circular plots. Stand density, basal area, and growing stock were estimated at the plot level. Diameter, height, crown dimensions, and crown damage were assessed on a subsample of 154 trees, from which increment cores were also collected. Ring-width measurements were used to calculate the Resilience index (Rs_3/6). Relationships among variables were evaluated using linear correlation and one-way analysis of variance was used for testing differences in crown damage and resilience index between categorized tree and stand variables. Mean crown damage was 24.4%, while the mean Rs_3/6 value of 0.90 indicated that radial growth had generally not returned to its previous level. Crown damage was negatively correlated with growth resilience. Trees in the 15–30 cm diameter class and the 21–40-year age class showed the lowest crown damage and highest resilience. The most favorable values of both indicators occurred at stand densities of 800–1200 trees ha⁻¹, while crown damage was lowest at basal areas below 15 m² ha⁻¹. Although the observed associations were moderate and should not be interpreted as causal effects, the combined use of crown condition and radial-growth recovery can support the identification of vigorous trees and inform adaptive, site-specific management of declining narrow-leaved ash stands. Full article

Background: The Warburg effect is a metabolic phenomenon observed in cancer cells that is characterized by aerobic glycolysis instead of mitochondrial oxidative phosphorylation as the primary mechanism of cellular energy generation. The exact benefit of such a metabolic switch is poorly understood, as aerobic glycolysis is thermodynamically more inefficient than mitochondrial oxidative phosphorylation. Case Presentation: Here, we present a case of a middle-aged individual with advanced stage 4 hepatocellular carcinoma with chronically low glucose levels measured in the 20 s to 40 s and completely asymptomatic. Upon examination, findings of sympathetic hyperactivity in the setting of hypoglycemia were absent, and mentation was completely intact. This occurred in the absence of any states or medications known to induce hypoglycemia; concurrently, the patient demonstrated hyperphagia, suggesting increased metabolic demand in the setting of an immense, overwhelming tumor burden. During these hypoglycemic intervals, the patient’s coagulation profile, including PT and international normalized ratio, remained within normal limits, suggesting sufficient residual hepatic parenchyma and glucogenic capacity. The patient’s glucose remained extremely low, refractory to correction with multiple dextrose, D5, and D10 administrations. This suggests chronic systemic habituation to malignant cell consumption of serum glucose leading to adaptations to this hypoglycemia in highly metabolically active organs, such as the brain, heart, liver, and kidneys. Discussion and Conclusions: This report highlights the clinical utility of recognizing this metabolic state in the setting of advanced-stage malignancy with significant tumor burden and how it affects hospital glucose management. Its early recognition will lead to improvements in meeting the patient’s metabolic demands while avoiding paradoxical exacerbation of lactic acidosis when providing guideline-directed oncological treatment. This metabolic state holds the potential to function as a surrogate marker, in conjunction with serum markers and imaging studies, for clinical identification of otherwise clinically silent advanced stage malignancies and for treatment escalation. Full article

Background: Ripretinib, a switch-control kinase inhibitor approved for advanced gastrointestinal stromal tumor (GIST), inhibits primary and secondary KIT and PDGFRA mutations. Real-world data from Western and Middle Eastern populations remain limited. We report outcomes from a molecularly characterized Israeli multicenter cohort. Methods: We conducted a multicenter retrospective cohort study across seven university-affiliated medical centers in Israel. Patients with advanced GIST receiving Ripretinib at any treatment line were eligible. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method, and response was assessed according to modified RECIST v1.1. Results: Sixteen patients were identified (median age, 67.5 years; 75.0% received Ripretinib in the fourth-line setting). KIT exon 11 mutations were present in 62.5% of patients, including five with secondary resistance mutations involving exon 13 or exons 17/18. Median PFS was 7.0 months (95% CI, 2.0–13.0) and median OS was 14.7 months (95% CI, 4.4–NR). Individual outcomes varied substantially, with PFS ranging from 2.0 to 60.2 months and OS from 2.2 to 60.2 months. Three patients achieved complete responses, with PFS of 20.0, 33.6, and 60.2 months. ORR was 56.3% (CR, n = 3; PR, n = 6) and DCR was 81.3%. No dose reductions or treatment discontinuations due to adverse events were documented; however, adverse events were recorded in only 4 of 16 patients. Conclusions: Ripretinib demonstrated clinical activity in this small, heavily pre-treated cohort. The relatively high ORR and wide variability in outcomes should be interpreted cautiously given the small sample size, retrospective design, and absence of central radiological review. Durable responses were observed in some patients with KIT exon 11 and secondary exon 17/18 mutations, but this exploratory observation does not establish a predictive molecular subgroup. Larger prospective studies with systematic molecular, radiological, and safety assessment are warranted. Full article

Background: Public health emergencies disrupt daily life and impose a heavy burden on mental health. Middle-aged and older adults are particularly vulnerable to the shocks caused by such emergencies, which may substantially increase their risk of depressive symptoms. Although social ties are closely related to mental health, little is known about how different types of social ties are associated with mental health in emergency contexts. Moreover, these associations have rarely been examined alongside broader contextual shocks. This study explores how different social ties are associated with lower depressive symptoms and examines the role of indirect disaster exposure. Methods: Data were drawn from the 2020 wave of the China Health and Retirement Longitudinal Study (CHARLS) and matched with urban cumulative confirmed cases. Using data from 15,897 respondents, we employed linear regression and bootstrap resampling to test whether life satisfaction statistically accounts for some of the associations between social ties, household financial stability, and depressive symptoms. The model also examined whether the association between life satisfaction and depressive symptoms varied with indirect disaster exposure. Results: Broader social participation (b = −0.242, p < 0.01), more positive perceived changes in intergenerational relationships (b = −0.536, p < 0.05), and better household financial stability (b = −1.637, p < 0.01) were associated with fewer depressive symptoms. Life satisfaction statistically contributed to the link between weak ties, financial instability, and depressive symptoms (b = −2.136, p < 0.01). Indirect disaster exposure strengthened the negative association between life satisfaction and depressive symptoms (b = −0.134, p < 0.01). Conclusions: During public health emergencies, depressive symptoms among middle-aged and older adults are associated not only with social ties and household financial stability, but also with the broader context of city-level disaster exposure. Depression prevention strategies need to consider both individual psychological resources and contextual disaster exposure to identify vulnerable populations and reduce mental health risk. Full article

Background: Lipoprotein(a) [Lp(a)] is a genetically determined, pro-atherogenic lipoprotein enriched in oxidized phospholipids and increasingly recognized as a key potential contributor to residual cardiovascular and inflammatory risk. However, data on its distribution and cardiometabolic associations in Middle Eastern populations remain limited. This study aimed to evaluate the prevalence of elevated Lp(a) and its association with type 2 diabetes (T2D), systemic inflammation, and ethnic variation in a multiethnic cohort. Methods: In this cross-sectional study, data from 2083 adults aged ≥ 18 years residing in Kuwait were collected through the Kuwait Diabetes Epidemiology Program (KDEP) at Dasman Diabetes Institute between 2011 and 2014 using random sampling. Plasma Lp(a) concentrations, cardiometabolic parameters, and high-sensitivity C-reactive protein (CRP) were measured. Elevated Lp(a) was defined as ≥ 50 mg/dL according to established clinical guidelines. Associations of elevated Lp(a) with T2D and CRP were assessed using multivariable Poisson regression models to estimate adjusted prevalence ratios. Results: The overall prevalence of elevated Lp(a) was 41.2%, exceeding global estimates. Significant ethnic variation was observed, with Arabs exhibiting the highest prevalence. After adjustment for potential confounders, individuals with T2D had a higher prevalence of elevated Lp(a) (APR = 1.166) and diabetes status significantly modified the association between CRP and elevated Lp(a) interaction (APR = 1.015), thus supporting a link between Lp(a) and systemic inflammation. Conclusions: Elevated Lp(a) was highly prevalent in this multiethnic Middle Eastern population and was independently associated with T2D and systemic inflammation. These findings support the emerging concept that Lp(a) may function as a molecular-inflammatory mediator potentially contributing to residual cardiovascular risk and highlight the importance of incorporating Lp(a) assessment into cardiometabolic risk stratification, particularly in high-risk populations. Full article

The Naglieri Nonverbal Ability Test–Individual Form (NNAT-I) is widely used to assess nonverbal reasoning while minimizing language demands, yet evidence regarding its psychometric properties in Turkish middle school students is limited. This study examined the reliability, convergent validity, internal structure, item functioning, and differential item functioning (DIF) of the NNAT-I in 1130 students aged 10–14 years attending schools across socioeconomic development strata in Aydın, Türkiye. Internal consistency, test–retest and alternate-form reliability, convergent validity, confirmatory factor analysis (CFA), Rasch analyses, multiple-group Rasch DIF analyses, and linear mixed-effects modeling were conducted. The NNAT-I demonstrated high internal consistency (Cronbach’s α = 0.93; McDonald’s ω = 0.94), strong test–retest and alternate-form reliability, and strong correlations with the Test of Nonverbal Intelligence–Third Edition (TONI-3) and Raven’s Standard Progressive Matrices (RSPM). CFA provided qualified rather than unequivocal evidence for a predominantly unidimensional structure, with model fit varying according to item response distributions and the treatment of structurally nonadministered responses. Rasch analyses of the calibrated items supported an ordered hierarchy of item difficulty, with all items showing Infit values within the prespecified descriptive reference range. After adjustment for multiple comparisons, DIF analyses identified significant gender-related DIF for only one item, while no items showed significant age-related DIF. Linear mixed-effects modeling showed that grade level and gender were significantly associated with NNAT-I scores, whereas chronological age was not independently associated with performance. These findings provide evidence regarding the reliability, convergent validity, internal structure, and item functioning of the NNAT-I in this Turkish middle-school sample, while also indicating that conclusions regarding unidimensionality should remain qualified. The findings underscore the importance of local psychometric evaluation before applying nonverbal measures in new educational and cultural contexts. Full article

Background/Objectives: School-based food and nutrition education is an important public health strategy for developing healthy dietary behaviors during childhood and adolescence. However, limited qualitative evidence describes how nutrition teachers, who are simultaneously responsible for school meals, perceive established educational priorities and emerging needs. This study explored current and future priorities for school-based food and nutrition education in South Korea. Methods: Two online focus group interviews were conducted with eight nutrition teachers working in elementary, middle, and high schools. The interviews were transcribed and analyzed using qualitative content analysis procedures. Results: Current priorities included foundational nutrition and food-related knowledge, balanced eating, environmental issues, low-sodium and low-sugar diets, understanding school meals, prevention of eating disorders and chronic diseases, and table manners and picky eating. Future needs centered on food choice and food literacy, sustainable diets, interdisciplinary education, and understanding diverse food cultures. Across themes, participants described a shift from primarily knowledge-focused instruction toward applied dietary competence, a broadening from individual disease prevention toward health and sustainability, and stronger integration of classroom education with school meals and other subjects. Conclusions: From the perspectives of the participating nutrition teachers, the findings provide formative evidence for curricula and interventions that combine foundational nutrition science with food-choice skills, age-appropriate preventive messages, sustainable dietary practices, and opportunities for behavioral application in the school meal setting. Future quantitative and intervention studies, including nationally representative samples, are needed before robust national priorities can be established. Full article

Research on how children develop emotion concepts is vital to successful, culturally sensitive social–emotional learning (SEL) programs that account for individual differences in the development of SEL skills. This study presents a thematic analysis of child emotion definitions and potential implications for SEL programs as an exploration of how children are taught about emotions and to center child voice in SEL research. It is the first, to the researchers’ knowledge, to link child emotion representation with SEL programs by analyzing emotion-focused program content through the lens of a child’s emotional representational system. A total of 1239 definitions produced by 49 children ages 8 to 11 (M_age = 9.24; SD = 0.75; 46.9% Female; 69% multilingual) were analyzed. Eight themes were identified in the definition corpus via thematic analysis and used as a framework to which 38 SEL programs were mapped. A majority of SEL programs addressed the following themes in the child-informed emotion framework: ‘interpersonal dynamics’ (addressed by 97% of programs), ‘cognitive states’ (95%), ‘performing an activity’ (87%), and ‘observable signs’ (71%) that referred to physical/sensory experience. When defining emotions, over 80% of children mentioned ‘interpersonal dynamics’ (e.g., rejection), ‘experiencing a non-social situation’ (e.g., a disappointing event), and ‘observable signs’ (e.g., sleeping). Findings offer preliminary insight into how a sample of children in middle childhood describe and make meaning of emotions, and prompt an exploratory discussion on emotion-focused content in SEL programs for middle childhood. Definitions collected constitute an emotion definition database available for future research on child emotion language. Full article

Background: Anterior ischemic optic neuropathy (AION) is a potentially vision threatening disorder that affects middle-aged and elderly individuals. The pathogenesis of the disease remains incompletely understood. However, the most universally accepted hypothesis suggests that a transient reduction in optic nerve head (ONH) perfusion, secondary to hypovolemia, nocturnal hypotension, or small-vessel disease, results in ischemic infarction of the anterior portion of the optic nerve. Case presentation: We present the case of a 61-year-old male patient with a history of arterial hypertension, type II diabetes mellitus, generalized atheromatosis, femoral bypass and stent implantation for chronic ischemia in his left leg, followed by brachial artery dissection that needed a prompt vascular intervention; he presented visual acuity loss in both eyes (BE), with the left eye (LE) being more affected than the right eye (RE). A complete ophthalmologic check-up was performed, and it revealed best-corrected visual acuity (BCVA) RE 0.5 Snellen, LE light perception, normal intraocular pressure (IOP), BE papillary edema and arteriovenous abnormalities. Visual field (VF) examination revealed RE inferior altitudinal defect and LE preabsolute scotoma. The diagnosis of BE anterior ischemic optic neuropathy and hypertensive retinopathy stage II was formulated. Following the aforementioned surgical procedures meant optimizing the patient’s critical vascular status, subsequent management of NA-AION systemic risk factors, along with implementing important lifestyle changes. No further cardiovascular events occurred, and visual field parameters remained stable at the three-year follow-up. Conclusions: Non-arteritic anterior ischemic optic neuropathy (NA-AION) remains a topic of interest for both ophthalmologists and neurologists worldwide. When confronted with a high-risk cardiovascular patient, a rapid and thorough systemic evaluation may prove beneficial. This management strategy could potentially contribute to maintaining a stable systemic outcome, despite major cardiovascular threats. Full article

Background: Polyendocrine Metabolic Ovarian Syndrome (PMOS), previously known as Polycystic Ovary Syndrome (PCOS), is one of the most common endocrine disorders affecting women of reproductive age and represents a major cause of infertility worldwide. It is associated with hormonal imbalance, ovulatory dysfunction, and metabolic disturbances, all of which can significantly impair reproductive outcomes and quality of life. We aimed to investigate the metabolic and hormonal markers in infertile women who had PMOS in one of the rapidly developing Middle Eastern countries. Methods: This was a retrospective observational cohort study conducted at the Military Medical Specialist Center in Qatar (2019–2024). Data were extracted from patient medical records, including demographic characteristics, clinical presentation, hormonal profiles, metabolic parameters, and details of fertility treatment. Women aged 18–40 years diagnosed with PMOS according to the Rotterdam criteria were included. Correlation coefficient analysis was performed to assess the associations between PMOS-related factors. Patients were categorized by BMI (normal, overweight, and obese). Results: The mean age of patients was 31.9 ± 5.3 years, and 43.8% of patients were obese. Primary infertility was more frequent than secondary infertility (61.8% vs. 38.2%). Women with secondary infertility were significantly older and had higher body mass index (BMI) (p = 0.001 and p = 0.01, respectively). Insulin resistance was prominent (mean Homeostatic Model Assessment for Insulin Resistance [HOMA-IR] of 4.04) and increased significantly with the increase in BMI (p = 0.01). BMI showed positive correlations with serum levels of glucose, insulin, HOMA-IR, and testosterone. Hormonal parameters were largely comparable between infertility groups, except for lower FSH levels in secondary infertility (p = 0.04). The proportion of PMOS based on the HOMA-IR category was 5.6% (HOMA-IR < 1.0), 23.4% (HOMA-IR 1–1.99), 20.2% (HOMA-IR 2–2.99), and 50.8% (HOMA-IR > 3.00). In PMOS patients, there was a significant association between obesity and HOMA-IR, with each 1-unit increase in HOMA-IR associated with a 14% increase in odds (crude odds ratio 1.14; 95% confidence interval 1.02–1.28, p = 0.02). Also, obesity was associated with low LH/FSH (crude odds ratio, 0.67; 95% CI, 0.45–0.99; p = 0.04). Results: The mean age of patients was 31.9 ± 5.3 years, and 43.8% of patients were obese. Primary infertility was more frequent than secondary infertility (61.8% vs. 38.2%). Insulin resistance was prominent (mean HOMA-IR 4.04) and increased significantly across BMI categories (3.0 in normal-weight vs. 4.8 in obese women, p = 0.01). BMI was positively correlated with HOMA-IR (r = 0.17, p = 0.02) and testosterone levels (r = 0.18, p = 0.01). Secondary infertility became more frequent with increasing BMI (p = 0.02). Each 1-unit increase in HOMA-IR was associated with a 14% increase in the odds of obesity (OR 1.14, 95% CI 1.02–1.28, p = 0.02). Conclusions: Among infertile women with PMOS, obesity and insulin resistance were prominent metabolic characteristics. These findings support routine screening for insulin resistance, particularly in overweight and obese women, together with weight management and individualized fertility treatment based on BMI and metabolic profiles. Full article

Background: Depressive symptoms have become a significant public health issue faced by middle-aged and older adults in China. Although previous studies have primarily focused on demographic and socioeconomic factors, the association between modifiable lifestyle behaviors and depressive symptoms still requires further investigation. Objective: To examine the associations between sleep duration, physical activity, digital participation, social participation, and depressive symptoms as well as life satisfaction among middle-aged and older adults in China. Methods: A cross-sectional analysis was conducted using data from the 2020 China Health and Retirement Longitudinal Survey (CHARLS). Depressive symptoms were defined as CES-D-10 scores ≥10, with 13,576 individuals included in the analysis sample. Adjusted prevalence ratios (aPRs) were estimated using modified Poisson regression, while ordinal logistic regression was employed to analyze life satisfaction. The analysis controlled for covariates such as demographics, socioeconomic status, and health status, and accounted for the complex sampling design. Results: The weighted prevalence of depressive symptoms was 44.5%. Sleep deprivation (<7 h/day) was significantly associated with elevated depressive symptoms (aPR = 1.49, 95% CI: 1.33–1.68); participation in recreational activities was significantly associated with reduced depressive symptoms (aPR = 0.86, 95% CI: 0.77–0.96); adequate physical activity was associated with a higher prevalence of elevated depressive symptoms (aPR = 1.17, 95% CI: 1.04–1.32); watching videos (aPR = 0.87, 95% CI: 0.76–0.99) and playing online games (aPR = 0.65, 95% CI: 0.50–0.83) were significantly associated with reduced depressive symptoms; and overall internet use was correlated with lower life satisfaction (OR = 0.90, 95% CI: 0.81–1.00). Women, rural residents, and low-income groups exhibited higher prevalence of elevated depressive symptoms. Conclusion: Sleep deprivation, as well as different types of social engagement, physical activity, and digital behavior, exhibit distinct associations with depressive symptoms in middle-aged and older adults. Behavioral intervention strategies targeting sleep hygiene, leisure activities, and tailored digital behaviors warrant further attention. Full article

Households have been reported to account for more than a third of food waste (FW) generated in the most developed and high-income countries. Despite this, there remains a limited understanding of the behavioural and sociodemographic factors driving household food waste (HFW) generation in most countries, including the Republic of Ireland (ROI). This study therefore examined how behavioural practices and sociodemographic characteristics independently and interactively influence HFW generation in the ROI. Data from a national online survey (n = 966 households; 3163 individuals) were analysed using hierarchical quantile regression. Households with children (Mixed households) reported the highest HFW (1177 g/household/week), and single-adult households recorded the highest per capita median waste (females = 596.0 g/cap/week and males = 496.5 g/cap/week). Behavioural factors were stronger predictors than sociodemographic characteristics. Reliance on date labels was the strongest predictor of HFW, associated with an additional 239 g/week. Each additional weekly shopping trip was associated with 140 g/week more waste, whereas using a shopping list was associated with 42 g/week less waste. Some effects were moderated by sociodemographic factors: reliance on date labels was more strongly associated with waste among adults aged 18–24, and shopping frequency more strongly associated with waste in middle-income households. The findings point to the value of reforming date labelling, supporting more planned shopping, and encouraging the active reuse of leftovers, with attention to differences across household groups. The findings also have direct implications for Ireland’s obligations under SDG 12.3 and the EU Waste Framework Directive. Full article

Objective: Our objective was to describe morphologic features and longitudinal changes observed on high-resolution vessel wall imaging (HR-VWI) in a selected retrospective case series of patients evaluated for suspected inflammatory intracranial vasculopathy. Methods: This retrospective case series included patients who underwent 3T intracranial HR-VWI for suspected inflammatory intracranial vasculopathy. Clinical and imaging data were collected from medical records and imaging archives. Three radiologists reviewed baseline and follow-up examinations for vessel wall enhancement (VWE) pattern and grade, wall thickness, luminal narrowing, arterial distribution, diffusion-restricted lesions, and susceptibility-sensitive findings. Analyses were descriptive and patient-level. Each patient contributed one baseline and one final examination to longitudinal summaries; intermediate scans characterized individual trajectories only. Results: Nineteen patients were included, and 17 underwent serial HR-VWI. Median age was 46 years (IQR, 35.5–60.0 years), and 11 patients were female. Follow-up HR-VWI was available in 17 patients over a median of 391 days (IQR, 237–1819 days; range, 15–4034 days). VWE was present in all patients, with a purely concentric pattern in 15/19 (78.9%). The middle cerebral and internal carotid arteries were involved in 17/19 and 13/19 patients, respectively. Among the 17 patients with paired examinations, VWE grade decreased in 13 patients (76.5%) and remained stable in four patients (23.5%), with the median decreasing from 3.0 to 1.0. Maximum wall thickness decreased in 16 patients and remained stable in one, with the median changing from 2.0 mm to 1.4 mm. Conclusions: In this selected retrospective case series of patients evaluated for suspected inflammatory intracranial vasculopathy, 3T HR-VWI commonly demonstrated concentric VWE and provided descriptive longitudinal information regarding enhancement evolution. These findings should not be interpreted as evidence of diagnostic performance. Full article

Background: Insulin resistance (IR) indices—C-reactive protein–triglyceride–glucose index (CTI), triglyceride–glucose (TyG) index, and weight-adjusted waist index (WWI)—are linked to cardiovascular disease (CVD), but their comparative utility in prediabetic populations remains unclear. To evaluate the associations and exploratory mediating roles of CTI, TyG and WWI with prevalent CVD in middle-aged and elderly patients with prediabetes. Methods: The study included 3121 NHANES participants aged ≥45 with prediabetes. Four machine learning algorithms identified key variables. Multivariable logistic regression and restricted cubic spline analyses examined the associations between IR and CVD. Model performance was assessed via receiver operating characteristic curves, net reclassification improvement, integrated discrimination improvement, calibration, and decision curve analysis. Subgroup analyses tested robustness. Mediation analysis assessed the mediating roles of IR in the WWI–CVD relationship. External validation used CHARLS. Results: Individuals in the highest tertiles of TyG, TyG–WWI, and CTI had approximately twofold higher CVD risk (ORs: 1.80–1.97). RCS showed a significant linear increase in CVD risk with higher IR index levels. In fully adjusted models, AUCs improved markedly over baseline: TyG–WWI 0.771 vs. 0.579. Mediation analyses indicated that CTI and TyG mediated 22.13–26.30% of the WWI–CVD association. Subgroup analyses and external validation in CHARLS supported the robustness. Conclusions: IR, as captured by TyG, TyG–WWI, and CTI, independently elevates CVD risk among middle-aged and older adults with prediabetes. WWI is associated with greater odds of prevalent CVD, potentially driven by adiposity accumulation, with CTI and TyG partially mediating this effect. Full article