Search Results (348)

Metabolic dysfunction-associated steatotic liver disease (MASLD) is defined by hepatic steatosis in individuals with at least one cardiometabolic risk factor, most commonly type 2 diabetes mellitus (T2DM). People with non-alcoholic fatty liver disease, even without other metabolic factors, have a higher risk of T2DM. MASLD includes isolated liver steatosis, metabolic dysfunction-associated steatohepatitis, fibrosis, cirrhosis, and MASH-related hepatocellular carcinoma. MASLD patients are also at a higher risk of developing T2DM than the general population. International guidelines recommend a stepwise approach for identifying those at high risk of fibrotic progression, using the FIB-4 index for initial screening, followed by transient elastography. The link between MASLD and T2DM is notable due to shared pathophysiological mechanisms, some of which are reversible with treatment used in T2DM. Many new glucose-lowering drugs have also proven effective in improving anthropometric and metabolic parameters, as well as the stage of hepatic steatosis and fibrosis. Recent evidence suggests that GLP-1RAs and SGLT2is have beneficial effects in MASLD patients with T2DM. Specifically, GLP-1RAs improve hepatic insulin signaling, modulate lipid metabolism, reduce inflammation, and decrease hepatocyte oxidative stress. European guidelines recommend resmetirom as a MASH-targeted therapy, if locally approved, for adults with non-cirrhotic MASH and significant liver fibrosis (stage ≥ 2) and GLP-1RAs in MASH, including compensated cirrhosis, but they should be used for their respective indications, such as T2DM and obesity. Given the post-COVID burden of MASLD and its high risk of liver fibrosis progression among T2DM patients, this review specifically provides an overview of the complex relationship between MASLD and T2DM. Additionally, it examines current understanding of liver fibrosis evaluation and the effects of novel treatment options, with a particular focus on glucose-lowering therapies and their effects on necroinflammation, hepatic fat accumulation, and fibrosis progression in patients with MASLD and T2DM. Full article

Background: Atrial fibrillation (AF) is frequently associated with cardiometabolic comorbidities, and increasing evidence suggests a close relationship between AF and liver disease, particularly metabolic dysfunction-associated steatotic liver disease (MASLD); however, the clinical patterns, hepatic phenotypes, and clinical implications of this association remain insufficiently characterized. Therefore, the aim of the present study was to characterize hepatic involvement in patients with paroxysmal AF by integrating a structured literature review with original clinical data. Methods: We performed a retrospective analysis of 253 patients admitted with paroxysmal AF between 2015 and 2025. Demographic data and associated diagnoses were collected with a specific focus on hepatic pathology. Patients were stratified according to the presence and type of liver disease, and descriptive statistics, bivariate analyses, and multivariate logistic regression were used to identify associations and independent predictors. Results: Liver disease was identified in 65.2% of patients, most commonly hepatic steatosis (46.2%), followed by liver cirrhosis or advanced liver disease (19.0%). Patients with liver disease had higher prevalences of type 2 diabetes mellitus, dyslipidemia, obesity, and alcohol consumption. Dyslipidemia (OR 4.51) and obesity (OR 2.54) were independent predictors of hepatic steatosis, whereas liver cirrhosis was inversely associated with age and serum lipid levels. Conclusions: Liver pathology is highly prevalent among patients with paroxysmal AF and is closely associated with adverse metabolic and clinical profiles. Recognition of distinct hepatic phenotypes may support improved risk stratification and multidisciplinary management in patients with AF. Full article

Background: Thyroid hormones regulate energy homeostasis, lipid/glucose metabolism, and protein turnover. Chronic Hepatitis C Virus (HCV) infection is highly associated with autoimmune hypothyroidism, which may have profound metabolic implications. This study evaluates thyroid dysfunction and anti-thyroid peroxidase (anti-TPO) autoimmunity in HCV patients and explores its potential metabolic implications in a high-prevalence region. Methods: In this comparative cross-sectional study adhering to STROBE guidelines, we enrolled 100 PCR-confirmed chronic HCV patients and 100 age/gender-matched controls from District Peshawar, Pakistan. Serum TSH, fT3, fT4, and anti-TPO antibodies were quantified. Multivariable logistic regression, adjusted for age, gender, and viral load, was used to compute adjusted odds ratios (aOR) with 95% confidence intervals (CI). Results: Thyroid dysfunction affected 41% of HCV patients vs. 12% of controls (aOR 5.2, 95% CI 2.8–9.6, p < 0.001), predominantly hypothyroidism (29% overall; 18% overt, 11% subclinical). Anti-TPO positivity was 38% in HCV vs. 8% in controls (aOR 6.7, 95% CI 3.1–14.5, p < 0.001). Anti-TPO titers correlated positively with TSH (r = +0.62, p < 0.001) and inversely with fT3/fT4. Subgroup analysis showed higher dysfunction in patients aged ≥40 years (52% vs. 28%, p = 0.012) and viral load ≥ 10⁶ IU/mL (48% vs. 32%, p = 0.041). We hypothesize that these findings may have significant metabolic implications, including impaired mitochondrial β-oxidation and insulin resistance. Conclusions: HCV infection is strongly associated with autoimmune hypothyroidism, which may amplify cardiometabolic risk. The paper has not explicitly identified metabolic parameters, including lipid profiles, indices of insulin resistance, and metabolomic signatures, and, therefore, any metabolic inferences are speculative and based on established thyroid and HCV pathophysiology. Routine thyroid screening pre- and post-DAA therapy is recommended, alongside metabolomic profiling to validate these proposed metabolic pathways. Full article

Insulin resistance (IR) is a central driver of cardiometabolic disease and an increasingly recognized modifier of inflammatory and vascular pathology. Beyond impaired glucose homeostasis, IR emerges from chronic, metabolically induced inflammation (“meta-inflammation”) and convergent cellular stress programs that propagate across tissues and organ systems, ultimately shaping endothelial dysfunction, atherogenesis, and cardiometabolic complications. Here, we synthesize multilevel links between insulin receptor signaling, intracellular stress modules (oxidative, endoplasmic reticulum, inflammatory, and fibrotic pathways), tissue-level dysfunction, and systemic inflammatory amplification. This work is a conceptual narrative review informed by targeted database searches and citation tracking, with explicit separation of mechanistic/experimental evidence from human observational and interventional data; causal inferences are framed primarily on mechanistic and interventional findings, whereas associative statements are reserved for observational evidence. We propose an integrative framework in which stress-response pathways are context-dependent and become maladaptive when chronically activated under nutrient excess and persistent inflammatory cues, generating self-reinforcing loops between IR and inflammation that accelerate vascular injury. This framework highlights points of convergence that can guide mechanistic prioritization and translational hypothesis testing. Full article

Background/Objectives: Obstructive sleep apnea (OSA) is often accompanied by metabolic syndrome (MetS), forming a high-risk phenotype with elevated cardiometabolic burden. The contribution of lifestyle behaviors—particularly eating mechanics and psychological eating cues—to disease severity remains unclear. This study examined independent associations of dietary behaviors and physical activity (PA) with OSA severity, sleep quality, and metabolic health. Methods: Forty-four OSA patients (mean age 38.3 ± 9.1 years; 89% male) underwent attended polysomnography, dual-energy X-ray absorptiometry, and metabolic profiling. Validated questionnaires assessed dietary behaviors, PA, and sleep quality. Hierarchical logistic regression identified predictors of MetS, severe OSA, and poor sleep quality. Results: The prevalence of MetS was 45%. Compared with those with OSA alone, participants with MetS demonstrated significantly greater central adiposity and more severe nocturnal hypoxemia, despite similar apnea–hypopnea indexes. In multivariable models, MetS was independently associated with higher body mass index (adjusted odds ratio [aOR] = 1.64; p = 0.008) and reward eating (aOR = 3.34; p = 0.041), whereas higher total PA was associated with reduced odds (aOR = 0.96; p = 0.026). Poor subjective sleep quality was significantly associated with younger age (aOR = 0.91; p = 0.037). For severe OSA, slow chewing was associated with significantly reduced odds (aOR = 0.24; p = 0.038), while emotional eating was associated with increased odds (aOR = 2.40; p = 0.048). Conclusions: This hypothesis-generating study identifies a high-risk OSA phenotype marked by metabolic dysfunction and hypoxemia. Eating speed (a proxy for mindful eating), emotional and reward-driven eating, and PA independently shape metabolic and respiratory outcomes. These findings support incorporating behavioral nutrition into multidisciplinary OSA management. Full article

Background and Objectives: Patients with type 2 diabetes mellitus (T2DM) and ischemic stroke present with endothelial, vascular and left ventricular (LV) myocardial dysfunction. We investigated the effects of treatment with either glucagon-like peptide-1 receptor agonists (GLP-1RA) or sodium-glucose contrasporter-2 inhibitors (SGLT-2i) on endothelial glycocalyx, arterial stiffness, and LV myocardial strain in patients with metformin-treated T2DM and a prior ischemic stroke. Materials and Methods: A total of 54 consecutive patients with T2DM and ischemic stroke who attended a cardiometabolic outpatient clinic in Athens, Greece, and received either GLP-1RA (dulaglutide; n = 27) or SGLT-2i (empagliflozin; n = 27) were enrolled in the study. We measured the perfused boundary region (PBR) of the sublingual microvessels, a marker of glycocalyx thickness, as well as carotid-femoral pulse wave velocity (PWV) and LV global longitudinal strain (GLS), at baseline and at 4 and 12 months of treatment. Results: Twelve months after treatment, all patients had reduced glycosylated hemoglobin and body mass index (BMI) (p < 0.001). Patients treated with dulaglutide showed a greater reduction in BMI (−11.8% vs. −4.8%, p < 0.001) compared to those treated with empagliflozin. Compared to baseline, all patients had reduced PBR, PWV and GLS (p < 0.001) after 12 months of treatment. However, empagliflozin presented a greater decrease in PWV (−14% vs. −10.9%, p = 0.041), while dulaglutide resulted in a greater increase in GLS (14.7% vs. 8.3%, p = 0.024) compared to empagliflozin. In all patients, the reduction in PBR at 12 months was correlated with a decrease in PWV and with an increase in GLS (p < 0.05). Conclusions: Both dulaglutide and empagliflozin improve cardiovascular function in T2DM patients with ischemic stroke. Dulaglutide appears to be more effective in the improvement of LV myocardial strain, whereas empagliflozin is more effective in reducing arterial stiffness. Full article

Type 2 diabetes mellitus (T2DM) is characterized not only by chronic hyperglycemia but also by profound adipose tissue dysfunction, including impaired lipid handling, low-grade inflammation, mitochondrial dysfunction, and extracellular matrix (ECM) remodeling. These adipose tissue alterations play a central role in the development of systemic insulin resistance, ectopic lipid accumulation, and cardiometabolic complications. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), particularly semaglutide, have emerged as highly effective therapies for T2DM and obesity. While their glucose-lowering and appetite-suppressive effects are well established, accumulating evidence indicates that semaglutide exerts pleiotropic metabolic actions that extend beyond glycemic control, with adipose tissue representing a key target organ. This review synthesizes current preclinical and clinical evidence on the molecular and cellular mechanisms through which semaglutide modulates adipose tissue biology in T2DM. We discuss depot-specific effects on visceral and subcutaneous adipose tissue, regulation of adipocyte lipid metabolism and lipolysis, enhancement of mitochondrial biogenesis and oxidative capacity, induction of beige adipocyte programming, modulation of adipokine and cytokine secretion, immunometabolic remodeling, and attenuation of adipose tissue fibrosis and ECM stiffness. Collectively, available data indicate that semaglutide promotes a functional shift in adipose tissue from a pro-inflammatory, lipid-storing phenotype toward a more oxidative, insulin-sensitive, and metabolically flexible state. These adipose-centered adaptations likely contribute to improvements in systemic insulin sensitivity, reduction in ectopic fat deposition, and attenuation of cardiometabolic risk observed in patients with T2DM. Despite compelling mechanistic insights, much of the current evidence derives from animal models or in vitro systems. Human adipose tissue-focused studies integrating molecular profiling, advanced imaging, and longitudinal clinical data are therefore needed to fully elucidate the extra-glycemic actions of semaglutide and to translate these findings into adipose-targeted therapeutic strategies. Full article

The increasing prevalence of metabolic dysfunction-associated fatty liver disease (MASLD) in children requires robust, non-invasive biomarkers to enable accurate disease staging and risk stratification. Elevated serum levels of homocysteine (Hcy) have emerged as potential risk factors for cardiometabolic disease in adults, including MASLD. In this observational retrospective study, we investigated the role of serum Hcy levels as a potential biomarker for disease severity and liver fibrosis in a pediatric cohort of 182 children with MASLD. In 89 patients, liver biopsy allowed the classification into metabolic dysfunction-associated steatohepatitis (MASH). Associations between Hcy, metabolic parameters, fibrosis scores, and histological features were examined, and the diagnostic performance of Hcy for liver fibrosis was evaluated using ROC analysis. Multivariate analyses identified elevated Hcy levels as independently associated with HOMA-IR (β = 0.55; p = 0.049), TG/HDL ratio (β = 3.23; p = 0.002), and liver fibrosis (β = 2.59; p = 0.04). Hcy showed a predictive accuracy of 81% for fibrosis. However, the combined diagnostic models of Hcy with non-invasive fibrotic scores (i.e., APRI and FIB-4) or TG/HDL ratio showed only a modest accuracy (AUC = 0.62–0.69). In conclusion, our data suggest that Hcy is associated with fibrosis and cardiometabolic risk. However, these results should be interpreted as exploratory and do not establish homocysteine as a diagnostic biomarker. Full article

Metabolic syndrome (MetS) is characterised by cardiometabolic risk factors and is closely associated with increased oxidative stress and chronic low-grade inflammation. MetS is largely driven by adverse lifestyle behaviours, particularly physical inactivity, and regular physical activity is recognised as a central strategy for its prevention and management. This study aimed to assess the long-term impact of a five-year follow-up period of physical activity on oxidative stress, inflammatory biomarkers, and cardiometabolic health in adults with MetS. Forty participants diagnosed with MetS (50% men, aged 55–75 years) were selected and stratified into two groups: those who increased their physical activity and those who reduced it during the intervention. Physical activity was assessed using metabolic equivalent task minutes per week (MET·min/week), and evaluations were performed at baseline, 3 years, and 5 years. Participants who increased physical activity showed a progressive reduction in reactive oxygen species (ROS) produced by peripheral blood mononuclear cells (PBMCs), together with a decrease in plasma malondialdehyde (MDA). Antioxidant enzyme activities, including catalase and superoxide dismutase, exhibited a favourable long-term profile, with recovery or maintenance of higher activity levels by the end of follow-up, reflecting enhanced endogenous antioxidant defence. Inflammatory status improved and was characterised by a reduction in myeloperoxidase (MPO) activity and a sustained increase in plasma interleukin-15 (IL-15). These participants also showed reductions in body weight, body mass index (BMI), waist circumference, fasting glucose, and glycosylated haemoglobin A1c (HbA1c), consistent with improved insulin sensitivity and metabolic control. Participants who reduced physical activity tended to show unfavourable trajectories in several biomarkers. Increasing physical activity over time is associated with substantial improvements in redox balance, inflammatory status, and cardiometabolic health in adults with MetS. These findings reinforce the central role of physical activity as a fundamental therapeutic component within lifestyle interventions aimed at mitigating metabolic dysfunction and preventing MetS progression. Full article

Metabolic dysfunction has emerged as a central driver of cardiovascular, renal, hepatic, and endocrine disorders, challenging traditional organ-specific disease models. Increasing evidence indicates that conditions such as obesity, type 2 diabetes, chronic kidney disease, heart failure, and metabolic dysfunction–associated steatotic liver disease frequently develop in parallel, reflecting shared upstream metabolic abnormalities rather than isolated pathologies. This narrative review synthesizes recent clinical, epidemiologic, biomarker, and therapeutic evidence to examine metabolic dysfunction as a unifying framework for multisystem disease, with particular focus on the cardiovascular–renal–hepatic–metabolic (CRHM) model. A targeted literature search of major biomedical databases was conducted to identify relevant studies published between 2020 and 2025, encompassing observational cohorts, randomized trials, and integrative reviews addressing cross-organ metabolic interactions. The reviewed evidence highlights consistent clinical overlap across organ systems, stage-dependent risk amplification and the utility of shared metabolic and inflammatory biomarkers in capturing multisystem vulnerability. In parallel, contemporary metabolic therapies demonstrate coordinated benefits across cardiovascular, renal, and hepatic domains, supporting the concept of common modifiable disease drivers. The reviewed evidence supports a shift from organ-based toward metabolic-centric frameworks for risk stratification and prevention. Viewing metabolic dysfunction as the organizing principle of cardiometabolic disease may improve recognition of multisystem risk, facilitate earlier intervention, and provide a more coherent foundation for precision and preventive medicine, in an era of growing cardiometabolic multimorbidity. Full article

Heart failure with preserved ejection fraction (HFpEF) accounts for more than half of the cases of HF worldwide. Among the different phenotypes, cardiometabolic HFpEF has the highest prevalence. Cumulative insults related to cardiometabolic comorbidities—obesity, hypertension and type 2 diabetes—create a milieu of metabolic derangements, low-grade systemic inflammation (i.e., metainflammation), endothelial dysfunction, and coronary microvascular disease. Emerging data indicate that the gut–heart axis is a potential amplifier of this process. Cardiometabolic comorbidities promote gut dysbiosis, loss of short-chain fatty acid (SCFA)-producing taxa, and disruption of the intestinal barrier, leading to endotoxemia and upregulation of pro-inflammatory pathways such as TLR4- and NLRP3-mediated signaling. Concomitantly, beneficial gut-derived metabolites (acetate, propionate, butyrate) decrease, while detrimental metabolites increase (e.g., TMAO), potentially fostering myocardial fibrosis, diastolic dysfunction, and adverse remodeling. SCFAs—acetate, propionate, and butyrate—may exert pleiotropic actions that directly target HFpEF pathophysiology: they may provide a CPT1-independent energy substrate to the failing myocardium, may improve lipid and glucose homeostasis via G protein-coupled receptors and AMPK activation, and may contribute to lower blood pressure and sympathetic tone, reinforce gut barrier integrity, and act as anti-inflammatory and epigenetic modulators through the inhibition of NF-κB, NLRP3, and histone deacetylases. This review summarizes current evidence linking gut microbiota dysfunction to cardiometabolic HFpEF, elucidates the mechanistic role of SCFAs, and discusses nutritional approaches aimed at enhancing their production and activity. Targeting gut–heart axis and SCFAs pathways may represent a biologically plausible and low-risk approach that could help attenuate inflammation and metabolic dysfunctions in patients with cardiometabolic HFpEF, offering novel potential therapeutic targets for their management. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a progressive spectrum of metabolic liver injury in which immune activation, metabolic stress, and stromal remodeling evolve in a tightly interdependent manner. Although early disease stages are dominated by metabolic overload, accumulating evidence indicates that immunometabolic rewiring and fibro-inflammatory amplification critically shape the transition toward metabolic dysfunction-associated steatohepatitis (MASH) and advanced fibrosis. This review synthesizes emerging insights into how hepatocyte stress responses, innate and adaptive immune circuits, and extracellular matrix-producing stromal populations interact to form a dynamic, feed-forward network driving disease progression. Particular emphasis is placed on the deterministic role of immune–fibrotic coupling in shaping clinical phenotypes, disease trajectory, and therapeutic responsiveness. Rather than focusing on individual molecular layers, we highlight how integrated clinical, imaging, and biomarker-informed frameworks can capture immune–fibrotic signatures relevant to risk stratification and precision intervention. Building on this systems-level perspective, we outline next-generation therapeutic strategies targeting immunometabolic circuits, cross-organ communication, and multi-system dysfunction. Finally, we discuss how future precision medicine—supported by integrative biomarker profiling and dynamic physiological assessment—may reshape MASLD management and improve long-term hepatic and cardiometabolic outcomes. Full article

Background: Visceral adiposity has emerged as a clinically relevant determinant of early cardiometabolic dysfunction in pediatric type 1 diabetes mellitus (T1DM), yet its assessment remains underutilized in routine practice. This study evaluated ultrasonographically measured epicardial adipose tissue thickness (EATT) and perirenal adipose tissue thickness (PrATT) as markers of metabolic risk, insulin sensitivity, and subclinical atherosclerosis in children and adolescents with T1DM. Methods: This cross-sectional study included 150 participants with T1DM and 152 age- and sex-matched healthy controls. Anthropometric data, biochemical parameters, hepatic steatosis grade, and insulin sensitivity indices (eGDR) were collected. EATT and PrATT were measured via standardized echocardiographic and abdominal ultrasonographic protocols. Carotid intima–media thickness (cIMT) was assessed as an indicator of subclinical atherosclerosis. Correlation and multivariable logistic regression analyses were performed to identify independent predictors of T1DM status and cardiometabolic risk. Results: Children with T1DM exhibited significantly higher PrATT and EATT values compared with controls (both p < 0.05). All eGDR indices were markedly lower in the T1DM group, reflecting reduced insulin sensitivity. PrATT and EATT showed strong or moderate correlations with hsCRP, hepatic steatosis, atherogenic index of plasma, and multiple anthropometric markers. Both visceral fat depots were positively associated with cIMT. Logistic regression identified PrATT, EATT, hsCRP, cIMT, and eGDR-BMI as independent predictors of case status. Subgroup analyses demonstrated more pronounced visceral adiposity and metabolic impairment among participants with BMI ≥85th percentile. Conclusions: Ultrasonographically measured PrATT and EATT provide valuable insight into early cardiometabolic risk in youth with T1DM, independent of BMI. Their associations with insulin resistance, inflammation, and subclinical atherosclerosis highlight their potential utility as accessible markers for early risk stratification in pediatric diabetes. Routine incorporation of visceral fat assessment may support earlier identification of high-risk individuals and more targeted preventive strategies. Full article

Circulating irisin, a myokine implicated in energy expenditure and adipose tissue regulation, has been increasingly studied as a potential biomarker of metabolic dysfunction. This study evaluated the relationship between serum irisin and metabolic indices, including the atherogenic index of plasma (AIP), the lipid accumulation product (LAP), and hypertriglyceridemic-waist (HTGW) phenotype in individuals with prediabetes (PreDM) and newly diagnosed type 2 diabetes mellitus (T2DM). A total of 138 participants (48 PreDM, 90 T2DM) were assessed for anthropometric, glycemic, and lipid parameters. Serum irisin levels were measured by enzyme-linked immunosorbent assay (ELISA) and correlated with insulin resistance indices (Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), Quantitative Insulin Sensitivity Check Index (QUICKI)), glycemic control (glycosylated hemoglobin A1c (HbA1c)), and composite lipid markers (total triglycerides-to-high-density lipoprotein cholesterol (TG/HDL-C)). Group differences were evaluated using non-parametric tests; two-way ANOVA assessed interactions between phenotypes and markers; multiple linear regression (MLR) and logistic regression models explored independent associations with metabolic indices and HTGW; receiver operating characteristic (ROC) analyses compared global and stratified model performance. Serum irisin was significantly lower in T2DM than in PreDM (median 140.4 vs. 230.7 ng/mL, p < 0.0001). Irisin levels remained comparable between males and females in both groups. Post hoc analysis shows that lipid indices and irisin primarily distinguish HTGW phenotypes, especially in T2DM. In both groups, irisin correlated inversely with HOMA-IR, AIP, and TG/HDL-C, and positively with QUICKI, indicating a possible compensatory role in early insulin resistance. MLR analyses revealed no independent relationship between irisin and either AIP or LAP in PreDM, while in T2DM, waist circumference remained the strongest negative predictor of irisin. Logistic regression identified age, male sex, and HbA1c as independent predictors of the HTGW phenotype, while irisin contributed modestly to overall model discrimination. ROC curves demonstrated good discriminative performance (AUC = 0.806 for global; 0.794 for PreDM; 0.813 for T2DM), suggesting comparable predictive accuracy across glycemic stages. In conclusion, irisin levels decline from prediabetes to overt diabetes and are inversely linked to lipid accumulation and insulin resistance but do not independently predict the HTGW phenotype. These findings support irisin’s role as an integrative indicator of metabolic stress rather than a stand-alone biomarker. Incorporating irisin into multi-parameter metabolic panels may enhance early detection of cardiometabolic risk in dysglycemic populations. Full article

Background/Objectives: Rosacea increasingly appears to involve systemic immune and metabolic disturbances rather than isolated cutaneous inflammation. To evaluate inflammatory, platelet, and oxidative–metabolic biomarkers in rosacea and explore their interrelations. Methods: 90 patients with rosacea and 90 healthy controls were evaluated for hematologic inflammatory indices—neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune–inflammation index (SII), pan-immune–inflammation value (PIV), mean platelet volume (MPV), and C-reactive protein (CRP)—along with oxidative–metabolic regulators including sirtuin 1 (SIRT1), sirtuin 3 (SIRT3), visfatin, and irisin. Logistic regression and receiver operating characteristic (ROC) analyses were used to identify independent predictors of rosacea, while inter-marker associations were evaluated using Spearman’s rank correlation. Results: Rosacea patients showed higher NLR, PLR, SII, PIV, MPV, CRP, and LDL cholesterol (p < 0.05) and lower SIRT1, SIRT3, visfatin, and irisin (p < 0.01). MPV independently predicted rosacea (OR = 7.24; AUC = 0.827), whereas SIRT1 inversely correlated with disease risk. SIRT1, SIRT3, and visfatin showed inverse correlations with HbA1c and waist-to-height ratio, while fasting glucose and HOMA-IR remained within normal ranges. Conclusions: Rosacea exhibits dual systemic activation, an inflammatory–platelet and an oxidative–metabolic axis bridging immune dysregulation, mitochondrial stress, and vascular dysfunction. Recognition of these pathways highlights the potential of redox-targeted and metabolic interventions beyond symptomatic treatment. Full article