Search Results (1,778)

Background: Vitamin D (25(OH)D) deficiency affects over one billion people globally and is associated with type 2 diabetes (T2D) and cardiometabolic diseases. However, causal relationships remain unclear, as vitamin D supplementation has shown limited benefit in reducing the risk of T2D. Genetic studies have identified variants that influence circulating 25(OH)D levels, but whether genetically determined vitamin D status predicts cardiometabolic outcomes remains uncertain. Methods and Results: Using multi-ethnic populations from the UK Biobank (471,861) and the Asian Indian Diabetic Heart Study (3486), we performed genome-wide univariate and polygenic risk score (PRS)-based bidirectional MR analyses to determine the causal association between vitamin D and T2D. A polygenic score of vitamin D–raising alleles did not affect the risk of T2D or cardiovascular disease. In contrast, a higher T2D PRS was strongly associated with an increased risk for 25(OH)D deficiency. Genetically instrumented per SD increase in T2D PRS was predicted to significantly (p = 9.5 × 10⁻³¹) reduce circulating 25(OH)D (β = −9.1 nmol/L; 95% CI: −8.9 to −9.3). The ancestry-specific univariate MR and sensitivity analyses confirmed that vitamin D levels reduced significantly with increasing T2D risk across all ancestries. Conclusions: Our findings suggest low circulating vitamin D levels are unlikely to causally predict T2D risk but may serve as a marker for secondary prevention in endocrine and cardiovascular health. Instead, genetic susceptibility to T2D appears to contribute to vitamin D insufficiency, which may lead to cardiovascular complications. Further studies are needed to clarify the mechanisms underlying vitamin D deficiency in diabetes. Full article

Background: Cardiometabolic diseases are shaped by complex interactions between biological and social determinants. While socioeconomic inequalities in cardiometabolic risk are well established, less is known about how these inequalities are distributed across multidimensional cardiometabolic phenotypes and whether they differ by sex. Objective: We aimed to examine sex differences in the socioeconomic gradient of cardiometabolic phenotypes using latent class analysis in a working-age population. Methods: A cross-sectional study was conducted in 3108 adults aged 18–65 years undergoing occupational health assessments in the Balearic Islands (Spain). Educational level was used as an indicator of socioeconomic position. Cardiometabolic risk was assessed using obesity, insulin resistance (METS-IR), metabolic dysfunction-associated steatotic liver disease (FLI), atherogenic index of plasma, and metabolic syndrome. Latent class analysis was applied to identify cardiometabolic phenotypes. Multinomial logistic regression models stratified by sex and interaction analyses were used to assess associations between educational level and class membership. Tests for linear trend and predicted probabilities were also estimated. Results: Four cardiometabolic phenotypes were identified: low-risk (40.8%), obesity-dominant (24.1%), dysmetabolic (19.3%), and high-risk multimorbid (15.8%). A clear socioeconomic gradient was observed, with lower educational attainment associated with a higher likelihood of belonging to adverse cardiometabolic profiles. This gradient was stronger among women. For the high-risk multimorbid class, the relative risk ratio comparing low vs. high educational level was 1.82 (95% CI 1.34–2.46) in men and 2.47 (95% CI 1.68–3.64) in women (p for interaction = 0.012). A significant linear trend across educational levels was observed in both sexes (p for trend < 0.001). Predicted probabilities further confirmed a steeper increase in high-risk profiles among women with lower educational attainment. Conclusions: Cardiometabolic risk is structured into distinct phenotypic profiles that are socially patterned. Socioeconomic inequalities are strongly associated with adverse cardiometabolic phenotypes, with a more pronounced gradient among women. These findings highlight the need for gender-sensitive strategies addressing social determinants to reduce cardiometabolic health inequalities. Full article

Adolescence is a developmental stage marked by dynamic interactions between diet, the gut microbiome and endocrine maturation, creating a physiological environment in which early metabolic disturbances can rapidly translate into long-term cardiovascular vulnerability. This narrative review summarises the latest research on the diet–microbiome–hormone axis in adolescents, focusing on the metabolic pathways through which microbial metabolites influence host physiology. Short-chain fatty acids (SCFAs), microbially transformed bile acids and postbiotic signalling molecules regulate enteroendocrine communication, insulin sensitivity, vascular function and inflammatory tone, thereby linking dietary exposures to early cardiometabolic alterations. Dysbiosis, driven by ultra-processed dietary patterns, low fibre intake and reduced microbial diversity, promotes metabolic endotoxemia, neuroendocrine imbalance and endothelial impairment, all of which are recognised as early indicators of cardiovascular disease. A distinctive contribution of this review is the integration of PF into the adolescent cardiometabolic framework. This emerging biotechnological process enables the controlled production of structurally defined bioactive compounds, including angiotensin-converting enzyme (ACE) inhibitory peptides, targeted prebiotic oligosaccharides, fermentable substrates that promote SCFA formation, microbially derived eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), phytosterols and purified postbiotics. These compounds modulate several regulatory pathways, such as the renin–angiotensin–aldosterone system, lipid and bile acid metabolism, gut barrier stability, inflammatory signalling and endocrine axes involving glucagon-like peptide-1 (GLP-1), peptide YY (PYY), leptin, insulin sensitivity and growth hormone/insulin-like growth factor-1 (GH/IGF-1) dynamics. By situating precision fermentation within the broader context of adolescent metabolic susceptibility, this review highlights its potential to support microbiome resilience, stabilise hormonal regulation and mitigate early cardiovascular risk. However, further adolescent-specific clinical trials and long-term safety assessments are required to translate these advances into effective public health strategies. Full article

Background/Objectives: Disease count alone does not show which multimorbidity combinations diversify or persist. We examined longitudinal changes in clinically recognisable multimorbidity profiles across three national ageing cohorts. Methods: Harmonised data from the China Health and Retirement Longitudinal Study (CHARLS), the English Longitudinal Study of Ageing (ELSA), and the U.S. Health and Retirement Study (HRS) were analysed. Eight physician-diagnosed chronic conditions were encoded as binary states, and wave-to-wave transitions (four windows in CHARLS and ELSA; five in HRS) were assessed within each cohort. State-level measures characterised accumulation, branching, persistence, and stabilisation sensitivity, supplemented by sensitivity analyses, BranchScore decomposition, prevalence-adjusted enrichment, and a disease-count-preserving permutation null model. Results: The analysis included 17,142 CHARLS, 10,272 ELSA, and 22,034 HRS participants, with baseline multimorbidity of 23.7%, 41.0%, and 58.5%, respectively. Transitions are concentrated around common profiles. One- and two-condition states (hypertension, diabetes, heart disease, chronic lung disease, psychiatric or emotional disorders) showed faster accumulation and greater branching; later persistent states were dominated by cardiometabolic-musculoskeletal combinations, particularly hypertension-heart disease-arthritis and hypertension-diabetes-arthritis. Targeted stabilisation produced modest perturbations exceeding random benchmarks. Count-preserving null models showed that early branching was largely structural, whereas selected lock-in states exceeded null expectations. Conclusions: Across three ageing cohorts, multimorbidity trajectories reflected disease composition as well as count. Because branching was strongly influenced by disease-count geometry, early branching states should be interpreted as structural cohort-level features of the cumulative framework rather than inherently predictive clinical entities. Selected cardiometabolic-musculoskeletal profiles were more persistent and may help frame integrated long-term management; patient-level prediction requires outcome-based studies. Full article

Background/Objectives: This study aims to estimate the prevalence of MASLD in a general outpatient population, describe associated metabolic risk factors, and evaluate liver fibrosis. Methods: We conducted a prospective, cross-sectional study at a tertiary hospital that included adults referred there for abdominal ultrasound for non-hepatic indications. Exclusion criteria were significant alcohol intake or known liver disease. Hepatic steatosis was assessed by ultrasound in all patients, and vibration-controlled transient elastography (VCTE) was performed in a subgroup. Clinical and laboratory data were collected. Comparisons used the chi-square test, Fisher’s exact test, and the Wilcoxon test, and logistic regression identified associated factors. Results: Hepatic steatosis was identified by ultrasound in 57.6% of the 182 patients, with most (93%) fulfilling the MASLD criteria. MASLD was diagnosed in 58.2% of patients based on ultrasound or VCTE findings of steatosis. Hepatic steatosis by ultrasound was associated with higher BMI (OR 1.30; 95% CI 1.18–1.43), hypertension (OR 1.92; 95% CI 1.04–3.53), glucose disorders (OR 3.33; 95% CI 1.60–6.92), and triglycerides (OR 1.01; 95% CI 1.00–1.03), while physical activity was protective (OR 0.86; 95% CI 0.26–0.99). Among 74 patients evaluated by VCTE, 8% had fibrosis (≥F1), which was more frequent in those with higher BMI and a number of cardiometabolic risk factors. Conclusions: This study reveals a high prevalence of MASLD and fibrosis among outpatients, supporting the use of abdominal ultrasound for opportunistic screening of MASLD and emphasizing the need for early risk stratification and referral. Full article

Gestational diabetes (GDM) is associated with long-term risk of diabetes and cardiovascular disease. Offspring of mothers with GDM also have elevated cardiometabolic risk in their lifetime. This article reviews risk factors that may predict progression to Type 2 or Type 1 diabetes after history of GDM, recurrence risk of GDM in a future pregnancy and discusses what evidence is available for risk mitigation in reducing long-term adverse health outcomes in both mothers with GDM and their children. Full article

Background/Aim: Berberine, an isoquinoline alkaloid widely used in traditional medicine, has attracted considerable interest for its capacity to modulate the gut microbiota and improve cardiometabolic outcomes. Although preclinical evidence is promising, no systematic review has previously synthesised evidence from randomised controlled trials (RCTs) in humans. This review aimed to evaluate the effects of berberine supplementation on gut microbiota and to explore associated cardiometabolic, inflammatory, and immunological changes. Methods: Prospectively registered in PROSPERO (CRD42024524143) and conducted in accordance with PRISMA guidelines, this review searched PubMed, Web of Science, Scopus, and Embase from inception to 10 January 2026. Eligible studies were RCTs in adults reporting gut microbiota outcomes following berberine supplementation. Methodological quality was assessed using the Cochrane Risk of Bias tool. Microbiota assessment methods, including sequencing platforms and bioinformatic pipelines, were systematically characterised across the included studies. Results: Seven RCTs enrolling 34 to 446 participants per intervention arm were included across diverse clinical populations—type two diabetes mellitus (T2DM), hyperlipidaemia, colorectal adenoma, psychiatric disorders, and Parkinson’s disease. Six of seven studies reported significant compositional shifts; the most extensively characterised changes—observed predominantly in T2DM populations—included enrichment of γ-Proteobacteria and depletion of butyrate-producing taxa, with specific taxa and the breadth of compositional changes varying considerably across clinical populations and sequencing methodologies. These shifts co-occurred with improvements in fasting glucose, lipid profiles, and inflammatory markers; however, causal inference cannot be established. Conclusions: Berberine consistently modulated gut microbial composition across heterogeneous clinical populations, with concurrent cardiometabolic and anti-inflammatory improvements. Compositional shifts were not uniformly favourable, and findings should be interpreted as hypothesis-generating. Geographically diverse, mechanistically focused RCTs are required to establish causality. Full article

Tryptophan (TRP) metabolism has emerged as a critical interface linking inflammation, immune regulation, oxidative stress, and cellular energetics. The kynurenine pathway, the predominant route of TRP degradation, is highly responsive to inflammatory stimuli and generates a spectrum of bioactive metabolites with divergent and context-dependent biological effects. Indoleamine 2,3-dioxygenase 1 (IDO1)-mediated TRP catabolism integrates immune activation with downstream metabolic signaling, influencing redox homeostasis, endothelial function, and mitochondrial energetics, in part by regulating nicotinamide adenine dinucleotide (NAD⁺) synthesis. Alterations in TRP metabolism are consistently observed across cardiometabolic diseases, including obesity, type 2 diabetes (T2D), atherosclerosis, myocardial infarction (MI), and heart failure with preserved ejection fraction (HFpEF), where they are associated with disease severity and adverse outcomes. Importantly, emerging data suggest that cardiometabolic phenotypes are determined not by pathway activation alone, but by the relative distribution of flux across downstream metabolic branches. Depending on the tissue compartment and stage of the disease, different biological effects may be contributed by redox-active kynurenine 3-monooxygenase (KMO)/3-hydroxykynurenine (3-HK)/quinolinic acid (QA) pathways, 3-hydroxyanthranilic acid (3-HAA)-mediated lipid and inflammasome regulation, microbiome-derived indoles, and NAD⁺-generating pathways. This review synthesizes current evidence using a branch-specific and context-dependent framework. We discuss the utility and limitations of the kynurenine-to-tryptophan ratio (KTR) as an upstream biomarker, the need for downstream metabolite panels, and therapeutic opportunities aimed at pathway modulation rather than broad inhibition. Future studies integrating temporal profiling, spatial and cell-specific approaches, large-animal models, and pathway-informed clinical trials will be essential to define causal mechanisms and enable precision therapeutic translation. Full article

Liver involvement is closely related to the progression and prognosis of heart failure (HF). This review evaluates the role of FIB-4, a non-invasive and easily calculable index of hepatic fibrosis, as a prognostic biomarker across different HF phenotypes, compared with other established biomarkers of HF. Current evidence demonstrates that elevated FIB-4 scores are closely associated with systemic venous congestion and right ventricular dysfunction and represent a strong independent predictor of adverse cardiovascular events, particularly in HFpEF. In contrast, in HFrEF and HFmrEF, its prognostic value appears less pronounced and more strongly influenced by concomitant primary liver disease, such as MASLD. In acute heart failure, FIB-4 reflects congestion severity and its dynamic reduction during hospitalization carries independent prognostic significance. Compared with NT-proBNP, FIB-4 provides complementary or superior prognostic information in HFpEF, particularly in the presence of predominant right ventricular dysfunction. Additionally, FIB-4 may serve as a screening tool to identify subjects at risk for HFpEF. In conclusion, FIB-4 is a promising tool for risk stratification in HF. However, further prospective studies are needed to establish standardized cut-off values, support its incorporation into clinical guidelines, and clarify its response to SGLT2 inhibitor therapy. Moreover, emerging cardio-metabolic therapies targeting both HF and hepatic fibrosis may further increase the clinical relevance of FIB-4 as a dynamic biomarker of the cardio–hepatic axis. Full article

Background: Vasomotor symptoms (VMS), particularly hot flashes and night sweats, are highly prevalent during the menopausal transition and have been increasingly associated with adverse cardiometabolic profiles. Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a major manifestation of systemic metabolic dysregulation and is rising globally. Emerging evidence suggests a potential overlap between menopausal symptom severity and MASLD risk; however, this relationship remains insufficiently characterized. Method: A scoping review was conducted in accordance with PRISMA-ScR guidelines to map the existing evidence on the association between VMS and MASLD. A comprehensive search of PubMed, Scopus, CINAHL, Cochrane Library, and MEDLINE was performed for English-language studies published between January 2015 and December 2025. Eligible studies included original research assessing both MASLD and menopausal symptoms. Data were extracted and synthesized narratively. Methodological quality was appraised using the CASP Cross-Sectional Studies Checklist. Results: Of 690 identified records, five cross-sectional studies met the inclusion criteria, comprising 106 to 5995 participants from Korea, Greece, and the United States. Across studies, moderate-to-severe VMS were consistently associated with increased MASLD prevalence or higher surrogate indices of hepatic steatosis. Women with more severe VMS demonstrated unfavorable metabolic profiles, including greater insulin resistance and elevated liver enzyme levels. Although adjustments for body mass index and hypertension attenuated some associations, the overall trend remained positive. Heterogeneity was observed in diagnostic tools and symptom assessment methods. Conclusions: Current evidence indicates a consistent association between VMS severity and MASLD in peri- and postmenopausal women. While causality cannot be inferred due to cross-sectional designs, VMS may represent a clinical marker of underlying metabolic and hepatic dysfunction. Longitudinal and mechanistic studies are warranted to clarify directionality and inform integrated screening strategies in midlife women. Full article

Background and Objectives: Obesity and insulin resistance are major contributors to cardiometabolic disease and type 2 diabetes mellitus (T2DM). This study evaluated the real-world effects of semaglutide on metabolic parameters, body composition, and cardiometabolic risk factors in people with obesity, with and without T2DM, and explored predictors of treatment response. Materials and Methods: This retrospective longitudinal observational study included 70 adults with obesity (42 with T2DM and 28 without T2DM) treated with semaglutide according to current clinical guidelines. The primary outcomes were changes in body weight, waist circumference, fasting plasma glucose, and glycated hemoglobin (HbA1c). Secondary outcomes included changes in lipid profile, insulin resistance indices, inflammatory markers, hepatic parameters, and body composition assessed by bioelectrical impedance analysis (InBody770). Results: Semaglutide treatment was associated with significant reductions in body weight (−9 kg), waist circumference (−8 cm), HbA1c (−1.1%), systolic blood pressure (−7.5 mmHg), visceral fat area (−30.1 cm²), and insulin resistance markers. Improvements in glycemic parameters were more pronounced in participants with T2DM. Skeletal muscle mass (SMM) was relatively preserved during treatment. Baseline HbA1c and visceral adiposity were independently associated with metabolic response. Conclusions: In this real-world observational cohort, semaglutide was associated with significant improvements in metabolic parameters, body composition, and cardiometabolic risk markers in people with obesity, with and without T2DM. Baseline metabolic characteristics may influence treatment response. Full article

Background/Objectives: Obesity is a chronic, multifactorial condition characterized by excessive adipose tissue that adversely affects health and continues to rise worldwide. It is strongly associated with cardiometabolic abnormalities that increase the risk of adverse outcomes, including type 2 diabetes and coronary heart disease. Methods: We conducted a multicenter, clinic-based cross-sectional analysis of electronic health records from 200,022 adults aged ≥20 years, who accessed nutritional and clinical laboratory services at Salud Digna between 1 January 2022 and 31 December 2025. Nutritional status was classified as normal weight or overweight/obesity using body mass index criteria. Metabolic health was assessed using five components of the National Cholesterol Education Program Adult Treatment Panel III criteria. Individuals were defined as metabolically unhealthy if they met three or more metabolic syndrome criteria. Results: Among participants, 78.17% of males and 79.73% of females were classified as overweight or obese. Metabolic unhealthiness was observed in 50.74% of males and 55.42% of females. The prevalences of metabolically healthy normal weight, metabolically healthy overweight/obesity, metabolically unhealthy normal weight, and metabolically unhealthy overweight/obesity were 18.55%, 31.09%, 3.90%, and 44.20%, respectively. Conclusions: These findings highlight a high burden of overweight/obesity and metabolic abnormalities in a large clinic-based sample of Mexican adults. While not nationally representative, this study provides important insights into the distribution of nutritional and metabolic health profiles in individuals accessing healthcare services, supporting the need for targeted prevention, early detection, and management strategies in clinical settings. Full article

Background/Objectives: Precision nutrition is moving beyond population-based guidance and isolated gene–diet interactions toward integrative models of dietary response. However, current approaches remain fragmented across nutrigenomics, microbiome research, multi-omics profiling, digital health, and machine learning. This review proposes the Nutri-Exposome Intelligence Framework as a conceptual, data science-driven model for integrating cumulative dietary, environmental, microbial, molecular, clinical, and digital exposures for precision chronic disease prevention. Methods: This conceptual review synthesizes the literature on precision nutrition, nutrigenetics, nutrigenomics, exposomics, gut microbiome research, multi-omics integration, wearable and biomarker-based monitoring, and machine learning in nutrition studies. Evidence was organized into a framework linking exposure assessment, host susceptibility, microbiome-mediated biotransformation, molecular response profiling, computational modelling, personalized intervention, and longitudinal feedback. Results: The proposed framework consists of seven interconnected layers: diet, environment, and lifestyle exposures; host genome and microbiome; multi-omics molecular responses; machine learning-based integration; risk prediction and responder stratification; personalized dietary intervention; and wearable and biomarker-based feedback. It positions the nutri-exposome as a cumulative exposure–response system and highlights how machine learning can support data harmonization, feature engineering, predictive modelling, responder classification, explainable interpretation, and adaptive refinement of dietary recommendations. Key applications include obesity, type 2 diabetes, cardiovascular disease, metabolic dysfunction-associated steatotic liver disease, cardiovascular–kidney–metabolic syndrome, and broader cardiometabolic prevention. Conclusions: Nutri-exposome intelligence offers a structured pathway for transforming complex nutrition data into predictive, explainable, and adaptive precision nutrition strategies. Implementation will require longitudinal and multi-ethnic cohorts, standardized metadata, causal validation, interpretable machine learning, ethical governance, and equitable access to support responsible clinical and public health translation globally. Full article

Coronary artery calcification (CAC) represents a clear sign of advanced atherosclerosis and a strong indicator of coronary artery disease burden and cardiovascular risk. Beyond its established prognostic value, CAC significantly influences plaque biology, lesion morphology, and the technical complexity of percutaneous coronary intervention (PCI). This review summarizes current knowledge on the mechanisms of vascular calcification, its clinical determinants, diagnostic assessment, and therapeutic implications. Vascular calcification is now understood as an active, regulated process involving osteogenic transdifferentiation of vascular smooth muscle cells, inflammatory signaling pathways, extracellular vesicle release, and disturbances in mineral metabolism. Distinct calcification phenotypes exert different effects on plaque stability: micro- and spotty calcifications are frequently linked to plaque vulnerability, whereas dense, sheet-like calcification is more typical of stable fibrocalcific lesions. The prevalence of CAC increases with age and differs between sexes, while cardiometabolic risk factors, chronic kidney disease, systemic inflammation, and genetic predisposition further contribute to its development. Noninvasive computed tomography remains the cornerstone for CAC detection and quantification, enabling reliable cardiovascular risk stratification. Intravascular imaging techniques, particularly intravascular ultrasound and optical coherence tomography, provide detailed characterization of calcified plaque morphology and support optimal procedural planning. In patients with heavily calcified lesions, intravascular imaging-guided lesion preparation and stent optimization represent the most effective strategy for improving PCI outcomes. Full article

Background and Objectives: Cardiometabolic risk factors frequently cluster and substantially increase the risk of cardiovascular disease. While high-density lipoprotein cholesterol (HDL-C) and systemic inflammation, measured by high-sensitivity C-reactive protein (hs-CRP), are independently associated with cardiometabolic risk, whether systemic inflammation modifies the association between HDL-C and cardiometabolic risk clustering (CMRC) remains unclear. This study aimed to examine the independent associations of HDL-C and hs-CRP with CMRC and to evaluate the multiplicative product interaction between HDL-C and natural log-transformed hs-CRP in relation to CMRC among middle-aged adults. Materials and Methods: This cross-sectional study used data from 2283 adults aged 40–64 years who participated in the 2024 Korea National Health and Nutrition Examination Survey. CMRC was defined as the presence of ≥2 cardiometabolic risk factors. HDL-C and hs-CRP were analyzed as continuous variables. Complex sample logistic regression analyses were performed to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs), including a multiplicative product interaction term calculated as HDL-C × ln hs-CRP. Results: The prevalence of CMRC was 46.4%. HDL-C was inversely associated with CMRC (OR = 0.946, 95% CI = 0.937–0.956, p < 0.001), whereas ln hs-CRP was positively associated with CMRC (OR = 1.224, 95% CI = 1.020–1.468, p = 0.030). The HDL-C × ln hs-CRP product interaction term was significantly associated with CMRC (OR = 1.005, 95% CI = 1.001–1.009, p = 0.008). This finding indicates that the association between HDL-C and CMRC may vary across levels of ln hs-CRP, but it does not indicate a direct association between HDL-C and ln hs-CRP. Conclusions: HDL-C and ln hs-CRP were independently associated with CMRC. The significant HDL-C × ln hs-CRP product interaction term suggests possible statistical effect modification of the HDL-C–CMRC association by systemic inflammatory status. These findings should be interpreted cautiously and do not establish a causal or mechanistic relationship. Full article