Search Results (6,680)

Polycystic ovary syndrome (PCOS) is associated with reproductive, metabolic, and inflammatory disturbances. Alterations in T-cell subpopulations—particularly increased T helper 17 cells (Th17) and decreased regulatory T cells (Treg)—have been reported in PCOS; however, data on normoandrogenic phenotype D remain limited. Hypoxia-inducible factor 1α (HIF-1α), a key regulator of hypoxic response, also influences immune and metabolic processes and may affect the Treg/Th17 balance. To assess Treg and Th17 abundance, HIF-1α expression within these cells, and their ratios in women with phenotype D PCOS compared with healthy controls. The study included 49 women with phenotype D PCOS and 40 controls comparable in terms of age and BMI. Anthropometric, hormonal, metabolic, and inflammatory parameters were evaluated. Peripheral T-cell subsets and intracellular HIF-1α expression were analyzed by multiparameter flow cytometry. Absolute numbers of Treg and Th17 cells did not differ between groups. However, PCOS patients showed significantly higher Treg/Th17 and HIF-1α-positive Treg/HIF-1α-positive Th17 ratios. HIF-1α-positive Treg cells correlated positively with adiposity and insulin resistance markers; however, after False Discovery Rate (FDR) correction, correlations no longer remained statistically significant. Despite normoandrogenemia, PCOS patients exhibited higher hs-CRP levels. Phenotype D PCOS is characterized by altered immune cell ratios rather than absolute T-cell differences, suggesting distinct immunological features and persistent low-grade inflammation. Full article

Atherosclerosis is a complex, multifactorial disease that progresses through distinct stages: initiation, progression, and complication, ultimately leading to acute coronary syndromes (ACS). Endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and macrophages are central players in this process, influencing plaque stability and vulnerability. Insulin-Like Growth Factor 1 (IGF-1), soluble-Klotho (S-Klotho), and the Growth Hormone Receptor exon 3 deletion polymorphism (GHRd3) have emerged as key modulators of vascular health, impacting these cellular components through various mechanisms. IGF-1 supports endothelial function, enhances VSMC survival and migration, and mitigates inflammation by inhibiting macrophage recruitment and activation, ultimately reducing the risk of plaque destabilization. S-Klotho, an anti-aging protein with potent anti-inflammatory and antioxidant properties, has been linked to vascular protection, with its deficiency associated with endothelial dysfunction, vascular calcification, and impaired VSMC survival. Evidence suggests that IGF-1 may enhance Klotho shedding, indicating a potential synergistic role in maintaining vascular integrity. This narrative review aims to outline the fundamental stages of atherosclerosis progression, consolidate current evidence on the roles of IGF-1 and S-Klotho in modulating key cellular components of atherosclerosis, and shed light on their potential involvement in plaque healing—an area that remains largely unexplored. By integrating established molecular mechanisms, we explore how these factors may contribute to endothelial integrity, VSMC survival, and macrophage activation and polarization, potentially shaping a more stable plaque phenotype and influencing future therapeutic strategies in cardiovascular disease. Full article

Background and Objectives: Severe COVID-19 frequently fulfills Sepsis-3 criteria and is characterized by thrombo-inflammation and endothelial injury. We evaluated whether a bedside endothelial activation index (EAI = D-dimer/fibrinogen) identifies biologically distinct phenotypes and relates to interleukin-6 (IL-6) response after therapeutic plasma exchange (TPE), and whether baseline IL-6 predicts a ≥50% IL-6 reduction. Methods: Retrospective single-center ICU cohort of adults with SARS-CoV-2 infection, sepsis-related organ dysfunction, and ≥1 TPE session (n = 51). Patients were stratified by median EAI (low vs. high). Outcomes included peri-procedural biomarker/physiology changes (post–baseline), IL-6 responder status (≥50% reduction), correlations with IL-6 reduction (%), and multivariable predictors of response. Results: Compared with low EAI (n = 25), high EAI (n = 26) had higher baseline D-dimer (6.2 vs. 2.2 µg/mL) and lower fibrinogen (2.9 vs. 7.1 g/L) (both p < 0.001). Low EAI showed larger CRP decreases (ΔCRP −84.0 vs. −2.3 mg/L; p = 0.001) and larger fibrinogen falls (Δ −3.1 vs. −0.4 g/L; p < 0.001), while high EAI had larger D-dimer decreases (Δ −2.5 vs. −0.6 µg/mL; p = 0.004) and a modest SOFA improvement (Δ −0.3 vs. +0.1; p = 0.026). IL-6 responders (n = 20) had higher baseline IL-6 than non-responders (365.2 vs. 47.1 pg/mL; p < 0.001). Baseline IL-6 independently predicted response (per doubling: OR 1.94, 95% CI 1.27–2.95; p = 0.002), while age reduced odds (OR 0.91/year, 95% CI 0.84–0.99; p = 0.032). IL-6 reduction correlated with ΔCRP (ρ = −0.41; p = 0.003) and ΔPaO₂/FiO₂ (ρ = 0.37; p = 0.01). Conclusions: EAI stratifies distinct thrombo-inflammatory patterns around TPE, while baseline IL-6 is the dominant predictor of achieving large IL-6 reductions. To emphasize the novelty and clarify the study objective, this exploratory analysis used a phenotype-stratified framework to test whether a simple bedside endothelial activation index could enrich biological response assessment to adjunctive TPE. The prespecified primary outcome was achievement of a ≥50% IL-6 reduction after completion of the TPE course; secondary outcomes included peri-procedural biomarker, oxygenation, SOFA, and ICU endpoints. Full article

Background/Objectives: Routine liver biopsies play an important role in monitoring liver allografts but carry non-negligible risks. This pilot study assesses the feasibility of dynamic long-axial field-of-view (LAFOV) [¹⁸F]FDG PET/CT as a non-invasive alternative to biopsy. Methods: Liver transplant (LTx) recipients meeting the inclusion criteria of ≥10 months post-transplantation and scheduled routine biopsy were prospectively enrolled, along with healthy controls. All participants underwent dynamic LAFOV [¹⁸F]FDG PET/CT, followed by biopsy in LTx recipients, who were stratified by inflammatory severity using the BANFF score. Hepatic kinetic parameters (K1, k2, k3, k4) and SUVmean/SUVmax were compared using Mann–Whitney U tests. Correlations were assessed using Spearman’s rank correlation. A p-value < 0.05 was considered significant. Analyses were performed in RStudio (version 2024.12.10563). Results: Sixteen LTx recipients (mean age 48.6 years; seven female, nine male) and eight healthy controls (mean age 35.4 years; six female, two male) were included. Healthy controls had mean k3 and k4 values of 0.0037 min⁻¹ ± 0.0003 min⁻¹ and 0.0019 min⁻¹ ± 0.0011 min⁻¹, respectively. LTx recipients showed significantly higher k3 and k4 values, both when including and excluding patients with biopsy-confirmed inflammation. Descriptive comparisons between LTx recipients with and without significant inflammation (n = 3) showed no clear differences. Spearman analysis showed no significant correlations between the BANFF score and kinetic parameters. The strongest degree of correlation was found between BANFF score and k3, indicating a moderate positive but non-significant association (k3: rs = 0.396, p = 0.128). Conclusions: Elevated k3 and k4 values in LTx recipients were not explained by allograft inflammation, suggesting altered FDG kinetics post-transplant. These differences may confound [¹⁸F]FDG PET interpretation. Larger studies are needed to assess the clinical applicability of dynamic LAFOV [¹⁸F]FDG PET/CT. Full article

Background: Manganese (Mn) is an essential trace element with antioxidant properties; however, excessive exposure may contribute to inflammation and vascular dysfunction. Hair analysis provides an indicator of long-term Mn exposure. This study evaluated the relationship between hair Mn levels, acute coronary syndrome (ACS), coronary artery disease (CAD) severity, and cardiovascular risk factors, with particular emphasis on metabolic status in a cardiometabolic population. Methods: Hair Mn concentration was measured using inductively coupled plasma optical emission spectrometry (ICP-OES) in 80 patients (mean age 67 ± 11 years; 28.8% women) undergoing coronary angiography for suspected ACS. Final diagnoses included stable CAD (N = 42) and ACS [ST-elevation myocardial infarction (STEMI) N = 17, non-ST-elevation myocardial infarction (NSTEMI) N = 12, and unstable angina (UA) N = 9]. CAD severity was quantified using the SYNTAX score and the Coronary Artery Surgery Study Score (CASSS). Associations with clinical variables were assessed using non-parametric tests and Spearman correlations. The median SYNTAX score was 13.8 (range 0.0–68.5), and the median hair Mn concentration was 0.22 ppm (range 0.01–1.65). Results: SYNTAX scores were higher in ACS than in stable CAD (p = 0.027), with the highest values observed in NSTEMI. Hair Mn levels did not differ among diagnostic groups and showed no association with CASSS or SYNTAX (R = −0.11; p = 0.348). No differences were detected with respect to sex, smoking, prior myocardial infarction, hypertension, hyperlipidemia, or type 2 diabetes. A modest inverse correlation was observed between hair Mn and body mass index (BMI) in unadjusted analysis (R = −0.25; p = 0.03), but this association was not robust after correction for multiple comparisons, suggesting a potential exploratory link between manganese homeostasis and cardiometabolic status. Conclusions: Although hair Mn concentration was not associated with angiographic indices of CAD severity or ACS subtypes, the observed relationship with BMI may indicate a role of Mn homeostasis in cardiometabolic regulation. Larger prospective studies are required to clarify these associations. Full article

Background: Frailty has been linked with systemic inflammation in elderly oncology patients. In this paper, we report the results of an analysis evaluating the association between blood cell biomarkers of inflammation and frailty in patients with operable non-small-cell lung cancer (NSCLC). Methods: A retrospective analysis was performed on patients undergoing surgery for NSCLC between March 2022 and March 2023. Frailty was assessed using the modified Frailty Index-5 (mFI-5) and 11 (mFI-11). Inflammation was evaluated using the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune–inflammation index (SII), and systemic immune–inflammation response index (SIRI), all calculated from preoperative assessments. Results: In this sample of surgical NSCLC patients (n = 106), frailty prevalence was 29.2% with mFI-11 and 17% with mFI-5. The log of the neutrophil-to-lymphocyte ratio (logNLR) emerged as the most significant predictor of frailty (OR of 3.13, 95% CI: 1.12–9.09, p = 0.03 for mFI-11 and 3.82, 95% CI: 1.28–11.11, p = 0.02 for FI-5). The platelet-to-lymphocyte ratio (PLR) was predictive only in the model assessing mFI-5. Furthermore, both the NLR and PLR showed an inverse linear correlation with frailty severity, a finding that remained consistent regardless of age, gender, disease stage, nutrition status, or comorbidity burden. Conclusions: Frail patients with operable NSCLC exhibit distinct inflammatory response patterns compared with those observed in non-frail lung cancer patients. Using these biomarkers could help identify patients suitable for preoperative interventions that could improve their postoperative course. However, further studies are needed to explore these preliminary findings prospectively and to understand the causal relationship between the observed association with frailty status and severity. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global health burden, yet effective therapeutic options remain limited. This study investigated the protective mechanisms of Astragalus membranous extract (AM) against high-fat diet (HFD)-induced MAFLD in mice using an integrated strategy combining network pharmacology, hepatic metabolomics, and 16S rRNA sequencing. UPLC–Q-Orbitrap–MS/MS identified 37 major constituents in AM, mainly phenolic acids and flavonoids. Iristectorin A, isorhamnetin, ononin, and rhamnocitrin were identified as key candidate compounds due to their relatively high abundance and confirmation as absorbed constituents in vivo. Network pharmacology and molecular docking indicated favorable interactions with hub targets (TNF, EGFR, and AKT1; binding energies < −5.0 kcal/mol) and highlighted the involvement of the AGE–RAGE signaling pathway and inflammation- and lipid metabolism-related processes. In vivo, AM significantly attenuated HFD-induced weight gain, decreased serum ALT and AST levels, and reduced hepatic lipid deposition. AM also alleviated oxidative stress by lowering malondialdehyde (MDA) and increasing superoxide dismutase (SOD) activity, while suppressing hepatic IL-1β and IL-6. Moreover, AM improved gut microbial homeostasis by restoring α-diversity and enriching beneficial genera, including Akkermansia and Bacteroides. Hepatic metabolomics further showed that AM partially normalized lipid metabolic disturbances, particularly glycerophospholipid and sphingolipid metabolism. Collectively, these results suggest that AM mitigates MASLD via a multi-component, multi-target mechanism, potentially through modulation of AGE–RAGE-associated inflammatory signaling and the gut–liver axis, supporting its development as a functional food-derived candidate for metabolic liver disorders. Full article

Nanomaterials (NMs) are increasingly utilized in drug delivery, diagnostic imaging, and therapeutic applications. However, their widespread use raises concerns regarding potential neurotoxicity, particularly for metal and metal oxide nanoparticles. Accumulating evidence indicates that these nanoparticles induce neurotoxicity through interconnected mechanisms, including excessive reactive oxygen species generation, activation of neuroinflammatory pathways, mitochondrial dysfunction, and disruption of blood–brain barrier integrity. These molecular events collectively lead to synaptic impairment, neuronal apoptosis, and progressive cognitive and behavioral deficits, with toxicity severity influenced by dose, exposure duration, and age. Given that in vitro models often fail to capture complex systemic interactions such as nanoparticle biodistribution, blood–brain barrier dynamics, and neuroimmune responses, this review places particular emphasis on in vivo studies to provide a more physiologically relevant understanding of nanoparticle-induced neurotoxicity. Importantly, a growing body of in vivo evidence demonstrates that natural bioactive compounds can mitigate these effects by targeting key pathogenic pathways, including oxidative stress, inflammation, and mitochondrial dysfunction, while preserving neuronal integrity. These findings highlight the therapeutic potential of natural bioactives as protective agents against nanoparticle-induced neurotoxicity and as candidates for broader neuroprotective strategies. This review summarizes the mechanistic basis of metal and metal oxide nanoparticle neurotoxicity and critically evaluates the protective role of natural bioactive compounds, with a focus on evidence derived from animal models. Full article

Background: Duchenne muscular dystrophy (DMD) is a rare, disabling, and life-threatening X-linked recessive disorder caused by mutations in the dystrophin gene. The current standard of care is treatment with corticosteroids, which aim to decrease inflammation-induced muscle damage and delay disease progression. Here, we aim to describe clinical, genetic, and diagnostic characteristics and evaluate current management practices of DMD patients in the Kingdom of Saudi Arabia (KSA). Methods: This was an ambispective (prospective and retrospective) observational multicenter study evaluating characteristics of patients aged 1–14 years with genetically confirmed DMD in the KSA. The variables of interest were demographics, genetic mutations, clinical characteristics, and initial management. The relationship between the age at diagnosis, initial management plan (standard of care), and age at initiation of treatment on disease outcomes was also evaluated. Results: A total of 226 patients (181 in the retrospective part and 45 in the prospective part) were enrolled. The most common type of genetic mutation was large deletions (134 patients, 59.3%). The median age of first symptom was 2.7 years (IQR: 2.0–4.6 years) and the median age at diagnosis was 7.0 years (IQR: 4.8–8.5 years). Among these patients, the most common initial symptoms were difficulty in walking (87.7%) and waddling gait (41%). The initial management plan for DMD patients involved medication (75.6%) and physical therapy (71.0%). The most frequently prescribed initial medications were vitamin D (82%) and corticosteroids (62.3%). In total, 6/226 patients (2.6%) received ataluren; they all had identified nonsense mutations. The median age of corticosteroid initiation was 7.1 years (IQR: 5.7–8.7). The median age at loss of ambulation (LoA) was 9.8 years (IQR: 8.0–11.4 years) in the non-treated patients; it was 10.1 years (IQR: 9.3–11.2 years) in the steroid-only group and 10.8 years (10.8, 10.8) in the combined ataluren and steroid treatment group. Discussion: Age of diagnosis and age of treatment initiation is relatively late in the KSA. However, early diagnosis and early treatment onset is associated with better clinical outcomes, mainly a delay in LoA. Therefore, there is an urgent need for raising awareness and enhancing early screening in the KSA. Full article

Skin aging is a complex biological process triggered by intrinsic and extrinsic factors, causing structural and functional deterioration, and its mitigation is a priority in cosmetology and functional food science. Skin fibroblasts, which mediate skin repair, wound healing and inflammation, are closely associated with aging. Sea cucumber collagen peptides exhibit prominent anti-aging, immunomodulatory and antioxidant properties, yet their mechanisms in ameliorating skin aging remain elusive, necessitating further exploration. This study verified the anti-skin aging efficacy of sea cucumber collagen peptides in D-galactose-induced aging mice, and explored whether the mechanism involves regulating endoplasmic reticulum (ER) stress in skin fibroblasts. Aging mice were gavaged with sea cucumber collagen peptides; skin moisture, barrier function and hydroxyproline content were measured, and skin morphology was observed. Immunofluorescence and Western Blot were used to detect ER stress-related proteins. Results showed that sea cucumber collagen peptides significantly improved aging mouse skin barrier function, elevated water and collagen fiber contents, and ameliorated the status of fibroblasts and prickle cells. The underlying mechanism may involve inhibiting ER stress in skin fibroblasts and enhancing prickle cell function. These findings confirm the peptides’ high bioavailability and potential as anti-aging functional food ingredients, providing insights for skin aging prevention. Full article

Metabolic abnormalities are frequently associated with hepatic steatosis and low-grade inflammation, yet the contributions of iron metabolism and genetic susceptibility are not fully understood. We aimed to investigate the relationship between serum ferritin, hepatic steatosis, metabolic risk clustering, and the PNPLA3 rs738409 gene variant in children. A total of 68 children aged 6–14 years underwent anthropometric, biochemical, imaging, and genetic assessment. Hepatic steatosis was present in 72.1% of participants, with fibrosis greater than F1 in 42.6%. Serum ferritin showed a strong correlation with echographic liver steatosis severity (ρ = 0.804, p < 0.001) and a moderate correlation with the number of metabolic risk components (ρ = 0.482, p < 0.001). The highest metabolic burden occurred in children with low iron and elevated ferritin. While PNPLA3 status did not independently predict ferritin levels, carriers had a significantly higher prevalence of hypertension (50.0% vs. 25.0%, p = 0.038) and a non-significant trend toward low HDL-C (65.0% vs. 42.9%, p = 0.070). Ferritin was associated with metabolic clustering and ultrasound-defined hepatic steatosis, acting as a nonspecific marker of combined metabolic and hepatic alterations. PNPLA3 genotype was not independently related to ferritin or fibrosis in early pediatric disease. Given the cross-sectional design and the relatively small sample size, these findings should be interpreted as exploratory and further studies including larger populations and direct inflammatory markers should be conducted. Full article

Introduction: Olives have been used in traditional Mediterranean medicine for thousands of years to address the causes of inflammation, ageing and cognitive health. Traditional preparations of olive include olive oil and olive leaf extract, which are major components of diets that contribute to maintaining cognitive function and reducing neurodegenerative disease risk. Aims of the study: This systematic review aimed to synthesise experimental and limited human evidence on olive biophenols in neurodegenerative disease models, identify the most studied compounds, characterise their mechanisms of action, and evaluate key translational barriers. Materials and methods: Following PRISMA 2020 guidelines and registered with PROSPERO (CRD420251252252), primary studies investigating the effects of well-characterised olive biophenols in neurodegenerative relevant in vitro, in vivo, or human models were systematically reviewed. Each study was assessed for its design, experimental model, mechanistic outcomes and reported limitations. Risk of bias was evaluated using validated tools (SYRCLE/OHAT/ToxR) appropriate for preclinical and experimental study designs. Results: Among the 25 studies, 7 (28.0%) examined oleuropein or oleuropein aglycone, 10 (40.0%) focused on hydroxytyrosol or its derivatives, and 9 (36.0%) investigated oleocanthal. Most studies employed in vivo animal models (57.7%), predominantly transgenic mouse models of AD and toxin-induced PD models. Oleuropein-based studies reported inhibition of amyloid-β and α-synuclein aggregation with behavioural improvements. Hydroxytyrosol primarily exerted antioxidant and anti-inflammatory effects with modest cognitive benefits. Oleocanthal showed the most consistent anti-amyloid and anti-tau activity, including enhanced amyloid-β clearance across the blood–brain barrier. Most studies show a moderate risk of bias due to incomplete reporting, randomisation and blinding. Conclusions: Olive biophenols demonstrate consistent neuroprotective effects in preclinical models; however, translation to clinical application remains limited by pharmacokinetic constraints, methodological heterogeneity, and insufficient human evidence. Full article

Atherosclerosis is a chronic inflammatory and metabolic disease driven by endothelial dysfunction, immune activation, vascular smooth muscle cell remodeling and aging-associated mitochondrial decline. Although lipid lowering remains the cornerstone of therapy, substantial residual inflammatory risk persists, highlighting the need for integrative regulatory targets. Sirtuin 1 (SIRT1), a NAD⁺-dependent deacetylase, has emerged as a central metabolic sensor linking energy availability to transcriptional control of inflammation, oxidative stress, mitochondrial biogenesis and cellular senescence. Experimental studies across endothelial cells, macrophages and vascular smooth muscle cells consistently demonstrate that SIRT1 activation preserves nitric oxide bioavailability, suppresses ROS-dependent inflammasome signaling, modulates macrophage polarization, inhibits ferroptosis and maintains mitochondrial integrity. These cell-type-specific effects converge to reduce plaque progression and enhance fibrous cap stability in preclinical models. However, SIRT1 activity is hierarchically regulated by AMPK signaling and NAD⁺ availability and is influenced by aging, metabolic dysfunction and environmental stressors, underscoring its context-dependent function. Despite promising mechanistic data, clinical translation remains limited, suggesting that precision modulation strategies may be required. This review synthesizes current evidence and proposes that SIRT1 functions as a metabolic–inflammatory integrator within the atherosclerotic arterial wall, representing a potential but context-sensitive target for future cardiovascular therapies. Full article

Neurodegenerative diseases of the central nervous system, such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis, represent a growing health challenge in ageing populations. Among the mechanisms underlying these disorders, increasing attention has been directed toward the role of cellular senescence. This process, triggered by chronic cellular and oxidative stress as well as DNA damage, leads to irreversible cell-cycle arrest and the development of the senescence-associated secretory phenotype (SASP). Within the central nervous system, the accumulation of senescent cells induces chronic inflammation, blood–brain barrier disruption, and progression of neurodegenerative processes. In this review, we present current evidence regarding the mechanisms of cellular senescence in the central nervous system, with particular emphasis on the role of SASP in neuroinflammation, vascular dysfunction, and neural tissue damage. Experimental and clinical data supporting the involvement of cellular senescence in the pathogenesis of Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis are discussed. The review also covers methods for identifying senescent cells in the brain, including molecular marker-based approaches and machine learning-based tools. Importantly, we discuss the methodological limitations of commonly used senescence markers, such as their limited specificity and the risk of false-positive detection, particularly in the heterogeneous cellular environment of the central nervous system. Strategies to improve detection reliability discussed in this review include the use of multimarker signatures, analysis of SASP components using qRT-PCR and ELISA, as well as transcriptomic approaches such as RNA sequencing and single-cell RNA sequencing. Furthermore, we analyze therapeutic strategies targeting senescent cells—senolytics, senomorphics, and SASP modulation—together with their limitations and associated clinical challenges. The collected evidence indicates that precise characterization of senescent cell populations in the brain is essential for the development of disease-modifying therapies for neurodegenerative disorders. Full article

Background: Chronic low-grade inflammation plays a central role in the pathogenesis of type 2 diabetes (T2DM) and its complications. Neopterin, a marker of macrophage activation and Th1-mediated immune response, has been associated with cardiovascular disease and metabolic disorders. However, its relationship with diabetic autonomic neuropathy remains insufficiently investigated. Methods: We conducted a cross-sectional study including 129 participants (93 with T2DM and 36 with obesity without carbohydrate disturbances). Clinical, anthropometric, and biochemical assessments were performed. Cardiovascular autonomic neuropathy was evaluated using Ewing cardiovascular reflex tests and sudomotor dysfunction scoring. Neopterin concentrations were measured in serum. Correlation, ROC, and logistic regression analyses were performed. Results: Neopterin levels were not significantly different between T2DM and obesity groups. No differences were observed in patients with versus without peripheral neuropathy, nephropathy, or retinopathy. However, neopterin levels were significantly higher in individuals with cardiovascular autonomic neuropathy (p = 0.013). Neopterin correlated with cardiovascular autonomic neuropathy score, sudomotor dysfunction, fasting glucose, fasting insulin, and HOMA-IR. It showed a moderate negative monotonic correlation with eGFR (Spearman’s rho = −0.41, p< 0.001). In multivariable logistic regression adjusted for age, HbA1c, BMI, eGFR, and diabetes duration, each 1-SD increase in neopterin was associated with 2.67-fold higher odds of cardiovascular autonomic neuropathy (95% CI 1.21–5.89; p = 0.015). Conclusions: Circulating neopterin is independently associated with cardiovascular autonomic neuropathy in T2DM but not with classical microvascular complications. These findings suggest a potential role of immune-mediated mechanisms in the pathogenesis of diabetic cardiovascular autonomic neuropathy. Full article