Search Results (165)

Background/Objectives: Gestational diabetes (GD) is a well known risk factor for future metabolic diseases. However, the long-term time-dependent risk of non-alcoholic fatty liver disease (NAFLD) remains unexplored. The aim of this meta-analysis was to quantify the long-term risk of NAFLD in women with previous GD and evaluate if the risk persists beyond the postpartum period. Methods: A systematic search was performed in PubMed using appropriate medical subject headings to identify trials evaluating the incidence of NAFLD among women with previous GD compared to those with normal glucose tolerance (NGT). Studies reporting adjusted risk estimates with a follow-up duration beyond pregnancy were included. Data were extracted and analyzed using relevant statistical methods, with the level of significance at p < 0.05. Results: A total of four studies (N = 2873) were included in the meta-analysis. Women with previous GD had a 2.46-fold higher odds of NAFLD compared to those with NGT (95% CI 1.88–3.23, p < 0.001). The slope for years since delivery was not significant (β = 0.001 per year, 95% CI −0.037 to 0.040, p = 0.901), indicating that the likelihood of NAFLD in women with prior GD did not change over time. Conclusions: GD is associated with a substantially increased and sustained risk of NAFLD, persisting decades beyond pregnancy. These findings identified GD as a potential early risk marker of future liver outcomes and highlight the need for long-term metabolic screening and preventive strategies for this high-risk population. Full article

In recent decades, the rate of kidney transplantation has risen significantly, leading to better outcomes in terms of cardiovascular and overall mortality for patients with kidney failure. Although kidney transplantation represents the most effective therapeutic option, it is not devoid of the risk of failure. Immunological and non-immunological risk factors are involved. These factors often interact and may act synergistically, ultimately influencing graft longevity and patient survival. Both contribute to long-term transplant outcomes; however, non-immunological factors, representing a significant clinical challenge, will be the focus of our review. Of the numerous non-immunological risk factors, for clarity and to avoid overextending the discussion, only those most closely associated with chronic kidney disease have been considered: hypertension, anemia, diabetes mellitus, proteinuria, electrolyte and acid–base imbalances, and impaired bone mineralization. Hypertension is reported in approximately 90% of kidney transplant recipients, often related to immunosuppressive therapy and residual renal dysfunction, and it is strongly associated with reduced graft survival. Anemia affects approximately 20–51% of these patients, contributing to cardiovascular morbidity and a more rapid decline in graft function, as does pre-existing diabetes mellitus. Proteinuria has a prevalence ranging from 7.5% to 45%, depending on the established target, and is a significant negative prognostic factor. Metabolic complications are also frequent; for example, hyperkalemia has an incidence of 25–44%, and metabolic acidosis has a prevalence of 12–58%. In our review, each of these factors is analyzed in terms of clinical impact, etiopathogenic mechanism, and available therapeutic management. Full article

Adult growth hormone deficiency (GHD) is linked to increased cardiovascular and metabolic risk due to oxidative stress (OS), endothelial dysfunction, and unhealthy body composition. Long-term systemic effects of recombinant human growth hormone (rhGH) therapy remain insufficiently defined. This study assessed the impact of 24-month rhGH replacement on OS, vascular markers, body composition, and bone mineral density (BMD) in adults with severe GHD. Fifteen adults with confirmed GHD received rhGH for 24 months. Serum insulin-like growth factor 1 (IGF-1), oxidized LDL (Ox-LDL), thioredoxin (Trx), 8-oxoguanine DNA glycosylase 1 (OGG1), E-selectin, intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1) were measured at baseline and 12 and 24 months. Body composition and BMD were evaluated by DXA. IGF-1 increased significantly at 12 and 24 months (p < 0.001). Ox-LDL markedly decreased (p < 0.00001), while Trx and OGG1 increased (p < 0.05). Levels of E-selectin, ICAM-1, and VCAM-1 declined, indicating improved endothelial function. Lean body mass and BMD increased, while body fat parameters showed heterogeneous changes. Lipid profiles were unchanged. Significant correlations were observed between vascular markers and adiposity, and between BMD, triglycerides, and IGF-1. A 24-month course of rhGH therapy improves redox balance, vascular function, and body composition in adults with severe GHD, supporting the use of redox and vascular biomarkers to monitor treatment efficacy. Full article

Kidney transplantation remains the ultimate treatment option for patients with end-stage renal disease. However, the global shortage in donor kidneys, exacerbated by challenges such as ischemia–reperfusion injury (IRI), reduces renal graft viability and negatively impacts post-transplant outcomes. Static cold storage, the gold standard of organ preservation, reduces metabolic demand but increases the risk of cold-induced mitochondrial dysfunction and IRI, especially in marginal kidneys. The introduction of machine perfusion techniques allows renal grafts and other solid organ grafts to be preserved at a wider range of temperatures. Organ preservation temperatures play an important role in determining post-transplant outcomes in the transplantation of the kidney and other transplantable solid organs. Therefore, determining the optimal preservation temperature may help increase organ utilization by avoiding unnecessary graft discards and increasing the safe use of marginal organs. This review discusses the impact of various preservation temperatures and methods of preservation on post-transplant outcomes in renal grafts and other organ grafts. Drawing from preclinical, clinical, and meta-analytic studies, we compare hypothermic (0–4 °C), moderate hypothermic (10 °C), subnormothermic (20–32 °C), normothermic (35–37 °C), and subzero preservation strategies, and cellular and molecular changes that occur in renal grafts and other solid organ grafts during preservation at these temperatures. Overall, temperature-controlled machine perfusion outperforms static preservation of renal grafts and other solid organ grafts from marginal and deceased donors, potentially expanding donor pools and improving long-term graft survival, and suggests the need for future research to determine optimal preservation temperature for renal grafts and other solid organ grafts to improve viability and post-transplant outcomes. Full article

Diabetic foot complications represent a major global health burden and arise from a multifactorial interaction between neuropathy, ischemia, infection, and impaired wound repair. Increasing evidence suggests that, beyond traditional vascular and metabolic risk factors, endocrine dysregulation plays a central role in shaping vascular dysfunction and tissue vulnerability in patients with diabetes. This narrative review provides an updated overview of the endocrine–vascular axis in the development, progression, and healing of diabetic foot ulcers (DFUs), integrating evidence from experimental and clinical studies identified through targeted searches of PubMed, Embase, and Scopus. We examine how alterations in insulin signaling, relative glucagon excess, adipokine imbalance, dysregulation of stress hormones, and thyroid dysfunction interact with chronic hyperglycemia, dyslipidemia, mitochondrial dysfunction, and low-grade inflammation to impair endothelial homeostasis. These disturbances promote oxidative stress, reduce nitric oxide bioavailability, and compromise microvascular perfusion, thereby creating a pro-ischemic and pro-inflammatory tissue environment that limits angiogenesis, extracellular matrix (ECM) remodeling, immune coordination, and effective wound repair. By linking pathophysiological mechanisms to clinical relevance, this review highlights potential biomarkers of endocrine–vascular dysfunction, implications for risk stratification, and emerging therapeutic perspectives targeting metabolic optimization, endothelial protection, and hormonal modulation. Finally, key knowledge gaps and priority areas for future translational and clinical research are discussed, supporting the development of integrated endocrine-based strategies aimed at improving DFU prevention, healing outcomes, and long-term limb preservation in patients with diabetes. 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

Obesity is a systemic metabolic disorder characterized by chronic low-grade inflammation and insulin resistance, with growing evidence indicating that the brain represents a primary and particularly vulnerable target organ. Beyond peripheral metabolic consequences, obesity induces region-specific structural, functional, and biochemical alterations within the central nervous system, contributing to cognitive impairment, dysregulated energy homeostasis, and increased susceptibility to neurodegenerative diseases. This narrative review examines key neurometabolic and neuroinflammatory mechanisms underlying obesity-related brain vulnerability, including downstream neuroinflammation, impaired insulin signaling, mitochondrial dysfunction, oxidative stress, blood–brain barrier disruption, and impaired brain clearance mechanisms. These processes preferentially affect frontal and limbic networks involved in executive control, reward processing, salience detection, and appetite regulation. Advanced neuroimaging has substantially refined our understanding of these mechanisms. Magnetic resonance spectroscopy provides unique in vivo insight into early neurometabolic alterations that may precede irreversible structural damage and is complemented by diffusion imaging, volumetric MRI, functional MRI, cerebral perfusion imaging, and positron emission tomography. Together, these complementary modalities reveal microstructural, network-level, structural, hemodynamic, and molecular alterations associated with obesity-related brain vulnerability and support the concept that such brain dysfunction is dynamic and potentially modifiable. Integrating neurometabolic and multimodal neuroimaging biomarkers with metabolic and clinical profiling may improve early risk stratification and guide preventive and therapeutic strategies aimed at preserving long-term brain health in obesity. 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/Objectives: Vitamin B₁₂ deficiency is increasingly recognized as a contributor in both vascular and neurodegenerative aging-related disorders. Its deficiency disrupts one-carbon metabolism, leading to impaired homocysteine (Hcy) cycling. Elevated Hcy is a well-established risk factor for vascular dysfunction. Previously, we established that elevated Hcy contributes to aging retinal diseases and plays a central role in blood retinal barrier (BRB) dysfunction. Building on this foundation, the present study examines how B-vitamin deficiency disrupts one-carbon metabolism and whether restoring these vitamins can serve as a preventive or therapeutic strategy. Since B-vitamins (B₆, B₉, and B₁₂) are crucial cofactors in the metabolism of Hcy, we investigated how dietary changes in these vitamins affect serum Hcy levels and retinal vascular integrity in mice. Methods: C57BL/6- Wild-type (WT) and cbs^+/− mice (Cystathionine Beta-Synthase heterozygotes, common mouse model for elevated Hcy) were fed specially formulated diets, which contained different levels of B-vitamins (normal, deficient (B-Vit (−)) or enriched (B-Vit (+)). Initially, two groups of mice were placed on either a normal or a deficient diet. After 12–16 weeks, the success of the diet regimes was confirmed by observing serum B₁₂ deficiency in the B-Vit (−) group, along with elevated Hcy levels. Subsequently, a subgroup of the B-Vit (−) mice was switched to an enriched diet. The BRB integrity was evaluated in living mice using fluorescein angiography (FA), optical coherence tomography (OCT), and in the perfused mice retinas with Western blot analysis of leaked retinal albumin and tight junction proteins (occludin and ZO-1) levels. Results: The B-vitamin deficiency caused significant drop in serum vitamin B₁₂ and an increase in plasma Hcy, leading to vascular leakage, altered retinal thickness, choroidal neovascular changes, increased retinal albumin leak, and decreased tight junction protein expression, indicating BRB disruption, which was restored with B-vitamin supplementation. Conclusions: a long-term deficiency of vitamins B₆, B₉, and B₁₂ can lead to disruptions in the BRB. However, supplementation with these B-vitamins has the potential to reverse these effects and help maintain the integrity of BRB. This under-score the significance of one-carbon metabolism for retinal health and suggests that ensuring adequate levels of B-vitamins may aid in preventing aging retinal diseases with BRB disruption such as diabetic retinopathy and age-related macular degeneration. Full article

Atrial fibrillation (AF) is the most prevalent sustained arrhythmia worldwide and is now increasingly regarded as a disease of chronic inflammation and progressive atrial fibrosis. Understanding of molecular mechanisms that mediate the linkage between systemic metabolic dysregulation, inflammation, and structural atrial changes is crucial for informing risk stratification and targeting of prevention strategies. This review provides evidence from 105 studies focusing on the contributions of transforming growth factor-β1 (TGF-β1), tumor necrosis factor-a (TNF-α), interleukin-6 (IL-6), galectin-3, and galectin-1 to cardiac fibrogenesis, atrial fibrosis, and AF pathogenesis. We also link metabolic syndrome to these biomarkers and to atrial remodeling, as well as echocardiographic correlates of fibrosis. TGF-β1 is established as the central profibrotic cytokine and promotes Smad-based fibroblast activation, collagen accumulation, and structural atrial remodeling. Its role is highly potentiated by thrombospondin-1 by turning latent TGF-β1 into its potent form. TNF-α and IL-6 also play an integral role in the inflammatory fibrotic continuum by activating NF-κB and STAT3 signaling, promoting fibroblast proliferation, electrical uncoupling, and extracellular matrix accumulation. Galectin-3 is a potent profibrotic mediator that promotes TGF-β signaling and is a risk factor for negative outcomes, whereas Gal-1 seems to regulate inflammation resolution and may exert context-dependent protective or maladaptive roles. Metabolic syndrome is strongly associated with excessive levels of these biomarkers, chronic low-grade inflammation, oxidative stress, and ventricular and atrial fibrosis. Chronic clinical findings show that metabolic syndrome (MetS) increases AF risk, exacerbates atrial dilatation, and is associated with worse postoperative outcomes. Echocardiographic data are connected to circulating biomarkers and are non-invasive for evaluating atrial remodeling. The evidence to date supports that atrial fibrosis should be considered an end point of systemic inflammation, metabolic dysfunction, and activation of profibrotic molecular pathways. Metabolic syndrome, due to its chronic low-grade inflammatory environment and prolonged levels of metabolic stress, manifests as an important upstream factor of fibrotic remodeling, which continuously promotes the release of cytokines, oxidative stress, and fibroblast activation. Circulating fibrotic biomarkers, in comparison with metabolic syndrome, serve separate yet interdependent pathways that help orchestrate atrial structural remodeling through the simultaneous process but can also provide a long-term indirect measure of ongoing profibrotic activity. The integration of these biomarkers with superior atrial imaging enables a broader understanding of the fibrotic substrate of atrial fibrillation. This combined molecular imaging approach can facilitate risk stratification, refine therapeutic decisions, and facilitate early identification of higher-risk metabolic phenotypes, thus potentially facilitating directed antifibrotic and anti-inflammatory therapy in atrial fibrillation. Full article

Metformin, the most widely prescribed oral antihyperglycemic agent, is established as the first-line therapy for type 2 diabetes mellitus (T2DM) owing to its efficacy, affordability, and safety. Increasing evidence indicates that its benefits extend beyond glycemic control, encompassing cardiovascular protection and diabetes prevention in individuals at elevated cardiometabolic risk. Mechanistic studies demonstrate that metformin exerts pleiotropic effects through activation of AMP-activated protein kinase, modulation of the gut microbiota, inhibition of pro-inflammatory and oxidative stress pathways, and improvements in endothelial function, lipid metabolism, and insulin sensitivity. These actions address core drivers of atherosclerosis and metabolic dysfunction, many of which occur independently of glucose lowering. In patients with T2DM, the cardiovascular benefits of metformin are well recognized, including reductions in all-cause mortality and cardiovascular events. In individuals without diabetes but at high cardiovascular risk—such as those with prediabetes, obesity, or metabolic syndrome—evidence is more limited, as most data are derived from subgroup analyses or trials with surrogate endpoints. Nonetheless, consistent signals suggest that metformin may delay the progression from prediabetes to overt diabetes and potentially confer vascular protection, particularly in carefully selected high-risk populations. Clinical trials and meta-analyses have demonstrated that metformin reduces incident diabetes by approximately one quarter in high-risk adults, with stronger effects observed in younger, overweight individuals, women with prior gestational diabetes, and those treated for longer durations. However, uncertainties remain regarding its long-term cost-effectiveness, optimal dosing strategies, and cardiovascular benefits in non-diabetic populations. The ongoing VA-IMPACT trial (NCT02915198) is expected to clarify whether metformin reduces major cardiovascular events in prediabetic patients with atherosclerotic disease. Taken together, metformin represents more than an antidiabetic drug. Its pleiotropic mechanisms, favorable safety profile, and low cost support its potential integration into broader cardiometabolic prevention strategies, including primary prevention. Expanding its role beyond diabetes management may offer a cost-effective, widely accessible intervention with significant public health impact. Full article

Background/Objectives: Sexual health is shaped by lifestyle factors alongside biomedical determinants. This review synthesises evidence on physiotherapy, balneology/peloidotherapy, and diet therapy as preventive and therapeutic adjuncts for female sexual dysfunctions and related gynaecological conditions. Methods: A structured narrative review of PubMed and Google Scholar (June–July 2025) was conducted by three independent reviewers using predefined keywords in English and Polish. Case reports, preprints, and studies before 2015 were excluded. From 7322 records, 47 studies met the inclusion criteria for qualitative synthesis. Results: Physiotherapy—particularly pelvic floor muscle training, multimodal manual therapy, neuromuscular electrical stimulation (including PTNS), magnetostimulation, short-wave diathermy, and capacitive–resistive monopolar radiofrequency—was consistently associated with reductions in dyspareunia, chronic pelvic pain, and urinary symptoms, with parallel improvements in sexual function and quality of life. Balneological procedures (brine baths/irrigations, crenotherapy, selected radon/sulphide/iodine–bromine applications) and peloidotherapy demonstrated analgesic, anti-inflammatory, and perfusion-enhancing effects, with signals of benefit in vulvodynia, endometriosis, and infertility support. Dietary measures—higher fruit intake (notably citrus), adequate vitamin D, targeted omega-3 use in PCOS, a Mediterranean dietary pattern, and prudent red-meat limitation—were associated with favourable endocrine–metabolic profiles and, in selected contexts, reduced disease risk. Conclusions: Integrating lifestyle–medicine modalities with standard care may meaningfully prevent and manage female sexual dysfunctions by addressing pain, perfusion, neuromuscular control, and endocrine–metabolic drivers. Implementation frameworks and high-quality trials are warranted to refine indications, dosing, and long-term effectiveness. Full article

Background: The transition from the term non-alcoholic fatty liver disease (NAFLD) to steatotic liver disease (SLD), an umbrella term for several related conditions, offers benefits, particularly in identifying cardiometabolic risk factors more effectively. However, the impact of alcohol consumption on liver disease progression remains significant, leading to the recognition of a new entity: MetALD (metabolic dysfunction-associated steatotic liver disease with moderate alcohol intake). Aim: This study aimed to compare characteristics associated with liver disease progression in diabetic patients diagnosed with metabolic dysfunction-associated steatotic liver disease (MASLD) versus those with MetALD. Materials and Methods: In this prospective study, 286 diabetic patients were followed for 12 months. All patients underwent transient elastography (TE) and ultrasound to assess hepatic steatosis. Participants were classified into MASLD and MetALD groups. The performance of fibrosis-4 index (FIB-4), and NAFLD fibrosis score (NFS) were also evaluated. Results: MASLD was diagnosed in 58.2% (167 patients), of whom 4.9% (7 patients) had TE values suggestive for liver cirrhosis. Among those with MetALD, 17.6% (21 patients) had TE values compatible with advanced fibrosis. MASLD subjects presented a slight decrease in liver fibrosis values from 6.58 ± 2.27 kPa to 6.03 ± 1.57 kPa in the 12 months. On the contrary, MetALD subjects had an increase of liver stiffness measurements (LSM) values from 11.83 ± 6.27 kPa to 12.24 ± 8.66 kPa. Conclusions: in diabetic patients, the coexistence of moderate alcohol intake and cardiometabolic risk factors (MetALD) is associated with more advanced liver fibrosis and impaired long-term glycemic control, compared to MASLD alone. Full article

Metabolomics research in schizophrenia has revealed consistent alterations across multiple biochemical domains, including energy metabolism, lipid composition, amino acid pathways, and oxidative stress regulation. The most reproducible findings include the dysregulation of the tryptophan–kynurenine pathway, disturbances in arginine/nitric oxide metabolism, alterations in phospholipid and sphingolipid profiles, reduced glutathione (GSH) in the brain, and elevated lactate levels, suggesting mitochondrial dysfunction. Antipsychotic treatment itself modifies a wide range of metabolites, complicating biomarker discovery. Although no single biomarker has yet achieved clinical utility, systematic reviews and Mendelian randomization studies provide evidence for validated biomarker panels and potential causal links between peripheral metabolite signatures and schizophrenia risk. The aim of this study is to characterize metabolic changes in patients diagnosed with schizophrenia, where each group received different non-invasive therapeutic methods and was compared to patients continuing standard pharmacotherapy without modification. The study results show that schizophrenia is associated with systemic metabolic disturbances affecting energy, amino acid, lipid, and redox pathways. Further development of research in this area requires comprehensive and long-term studies integrated with modern imaging and analytical techniques. Full article

Microplastics represent an emerging threat to aquatic environments and organisms, as they infiltrate water systems, are ingested by marine species, and cause physical harm, endocrine disruption, and bioaccumulation up the food chain, potentially impacting biodiversity and human health. Aquatic ecosystems face considerable harm from microplastic pollution because fish in the early developmental stages, including embryos, larvae, and juveniles, are more susceptible due to their immature physiological and detoxification systems. This review aims to comprehensively explore the impacts of microplastics on the early life stages of fish. Aquatic environments receive primary and secondary MPs from urban runoff and industrial waste, together with degraded plastics, which affect fish embryos and larvae via direct ingestion, surface adhesion, and trophic transmission pathways. The physical impact of MPs causes digestive tract blockages that reduce hatching success and create developmental problems in fish organs, but chemical toxicity develops from plasticizers, heavy metal leaching, and pollutant adsorption, which causes oxidative stress, endocrine disruption, and metabolic dysfunction. Survival rates decrease because exposure causes fish to perform poorly during swimming activities and make limited efforts to avoid predators. The small dimensions and high chemical reactivity of MPs increase their bioavailability, which promotes tissue penetration and leads to accumulation at different levels of the food chain. This comprehensive review emphasizes that we need to establish uniform detection protocols, long-term exposure research, and effective strategies to control MP pollution. The resolution of these difficulties remains essential for protecting fish populations, as well as for protecting biodiversity and minimizing seafood contamination risks to human health. Full article