Sweet potato (Ipomoea batatas L.) is a nutrient-dense tuber often used in traditional diabetic treatment. This research compares the antidiabetic potential of three sweet potato varieties: orange-fleshed (OFSP), purple-peel white-fleshed (PPWSP), and white-peel white-fleshed (WPWSP), utilising in vitro and in vivo techniques. Sweet potatoes (OFSP, PPWSP, and WPWSP) boiled at 100°C for 20 minutes were incorporated into formulated diets and administered to streptozotocin-induced diabetic rats for 14 days. Aqueous extracts of the diets were tested in vitro for antioxidants and phytochemicals. Glycaemic control parameters, lipid profiles, oxidative stress indicators, and pancreatic histology were investigated. Gene expression analysis was performed on critical diabetes-related pathways. OFSP showed significant strong anti-diabetic benefits, including better glycemic control, weight maintenance, lower HOMA-IR scores, and lowered α-amylase and α-glucosidase activity. OFSP-fed rats had higher insulin, glycogen, and hexokinase activity than those given PPWSP and WPWSP. OFSP decreased mRNA expression of DPP-4 while increasing GLP-1 expression. OFSP also improved lipid profiles, increasing HDLc while decreasing LDLc and triglycerides more than other varieties. Histopathological examination revealed restorative effects in pancreatic beta cells. OFSP demonstrated more pronounced antidiabetic effects compared to PPWSP and WPWSP, particularly in terms of glycemic control, insulin regulation, and lipid profile improvement. These findings suggest that OFSP may offer significant potential for diabetes management. However, further clinical studies are needed to validate these results and explore the practical dietary applications of OFSP in diabetes control.

Zebrafish (Danio rerio) have become indispensable models for advancing our understanding of multiple metabolic disorders such as obesity, diabetes mellitus, dyslipidemia, and metabolic syndrome. This review provides a comprehensive analysis of zebrafish as a powerful tool for dissecting the genetic and molecular mechanisms of these diseases, focusing on key genes, like pparγ, lepr, ins, and srebp. Zebrafish offer distinct advantages, including genetic tractability, optical transparency in early development, and the conservation of key metabolic pathways with humans. Studies have successfully used zebrafish to uncover conserved metabolic mechanisms, identify novel disease pathways, and facilitate high-throughput screening of potential therapeutic compounds. The review also highlights the novelty of using zebrafish to model multifactorial metabolic disorders, addressing challenges such as interspecies differences in metabolism and the complexity of human metabolic disease etiology. Moving forward, future research will benefit from integrating advanced omics technologies to map disease-specific molecular signatures, applying personalized medicine approaches to optimize treatments, and utilizing computational models to predict therapeutic outcomes. By embracing these innovative strategies, zebrafish research has the potential to revolutionize the diagnosis, treatment, and prevention of metabolic disorders, offering new avenues for translational applications. Continued interdisciplinary collaboration and investment in zebrafish-based studies will be crucial to fully harnessing their potential for advancing therapeutic development.

The precise pathogenic mechanism of long-term detrimental effects on mothers and infants resulting from gestational diabetes (GDM) remains unclear. This study aimed to examine the long-term detrimental consequences of GDM on mothers and newborns, particularly the impact of glucose concentration variations on vascular endothelial cells and its possible pathogenic mechanisms.

An analysis was conducted on the clinical data of 68 healthy pregnant women and 67 pregnant women diagnosed with GDM. Human umbilical vein endothelial cells (HUVECs) were obtained from six pairs of pregnant women for transcriptomic sequencing and analysis, which were concurrently analysed with existing databases. The study examined the effects of varying glucose concentrations on HUVECs, incorporating relevant biological experimental verifications, and assessed oxidative stress, inflammation, and the TGF-β signalling pathway.

Clinical data analysis indicated that in patients with gestational diabetes mellitus, early pregnancy hyperglycemia is significantly linked to adverse pregnancy outcomes, even when blood glucose levels are well-controlled. Transcriptomic sequencing revealed significant alterations in the gene expression of HUVECs under GDM conditions, highlighting enrichment in genes associated with metabolism, inflammation, oxidative stress, and diabetes signalling pathways. Cellular experiments indicated that a transition in glucose concentration from elevated to reduced levels can result in damage and dysfunction in HUVECs, elevate ROS levels, and activate the TGF-β signalling pathway. Additionally, injured HUVECs release CTGF through the TGF-β signalling pathway, influencing the extracellular matrix and surrounding cells.

The findings demonstrate that alterations in glucose concentration, particularly the shift from high to low levels, can lead to vascular endothelial cell dysfunction, increase ROS levels, and are associated with the TGF β/SMAD3 signalling pathway. Furthermore, compromised HUVECs can influence the microenvironment via their secretions, potentially jeopardising the health of both the mother and foetus.

The hyperglycemic state in diabetes mellitus induces oxidative stress and inflammation, contributing to diabetic tissue damage and associated complications. Astaxanthin, a potent antioxidant carotenoid, has been investigated for its potential to prevent and manage diabetes across various species; however, its effect on client-owned dogs remains poorly studied. This study explored the impact of astaxanthin supplementation on canine diabetes mellitus using a proteomics approach. A total of 18 client-owned dogs were enrolled: 6 dogs with diabetes mellitus and 12 clinically healthy dogs. The diabetic dogs received their standard treatment regimen along with daily oral supplementation of 12 mg of astaxanthin (1.5-2.4 mg/kg) for 90 days. Plasma samples were collected at the beginning and end of the study period for proteomics analysis. After astaxanthin supplementation, significant alterations in the expression of proteins associated with the complement system, coagulation cascade, JAK-STAT signaling, and protein kinase C signaling (all of which contribute to inflammation and oxidative stress) were observed. Astaxanthin exhibited potential for reducing diabetes-associated complications, such as insulin resistance, vascular dysfunction, nephropathy, and cardiac issues, even though it did not affect clinical parameters (hematology, plasma biochemistry, blood glucose, and serum fructosamine). These findings suggest that astaxanthin may be a valuable complementary therapy for managing diabetes-related complications in canines.

Artocarpus heterophyllus Lam. (Jackfruit) is a common plant in the genus Artocarpus of Moraceae family, and its fruit has a variety of nutritional values. Jackfruit polysaccharides are considered to be one of the main bioactive compounds in jackfruit, which have immunomodulatory, anticancer, antioxidant, hepatoprotective, hypoglycemic, antibacterial and other health benefits. This article reviews the research progress in the extraction, purification, structural characteristics and health benefits of jackfruit polysaccharides. Mechanisms of action based on in vivo and in vitro experiments are also elucidated. The structural-activity relationships of jackfruit polysaccharides are discussed in depth, and their potential application values are revealed by combining the relationships between molecular structures and health benefits. This article aims to address the key issue of how to obtain jackfruit polysaccharides that feature both high yield and significant health benefits, and to conduct an in-depth exploration of the development pathways for their transformation into new health products, as well as their practical applications in the sustainable utilization of plant resources. Through a comprehensive analysis of the current research status and development trend, this article puts forward a new prospect for jackfruit polysaccharides research, hoping to provide innovative ideas and practical guidance for follow-up related work.

Insulin glargine is a long-acting drug and the first synthetic insulin to mimic human metabolism. The safety of insulin glargine in the real world remains to be further investigated. This study aims to analyze insulin glargine-related adverse events (ADEs) to guide its safe clinical use.

This study collected ADE reports from the FDA Adverse Event Reporting System (FAERS) between the first quarter of 2004 and the third quarter of 2024, where insulin glargine was identified as the primary suspect drug. Four disproportionate analytical methods were employed to analyze positive signals for drug-related ADEs, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). The study also describes the time to onset of ADEs and uses the Weibull distribution to analyze the temporal trend of ADEs occurrence over time.

This study included 97,350 ADE reports, containing 228,258 ADEs, and identified 130 ADEs with positive signal. The study confirmed several known ADEs, such as hypoglycemia, injection site pain and acquired lipodystrophy. Additionally, several unexpected ADEs were identified, including pancreatic neoplasm, medullary thyroid cancer, and bone marrow tumor cell infiltration. 28.13% of ADEs occurred within the first month. The Weibull distribution indicated that the occurrence of ADEs decreased over time.

This study explored the real-world safety of insulin glargine and revealed several unexpected ADEs. These findings provide new insights into the safety profile of insulin glargine for clinicians."

Isoliquiritigenin (ISL), a major chalcone-type flavonoid produced predominantly from liquorice roots (Glycyrrhiza species), has exceptional therapeutic potential across a wide range of pharmacological activities. ISL has numerous benefits including antioxidant, anti-inflammatory, antidiabetic, cardioprotective, hepatoprotective, neuroprotective, and anticancer activities. This review gathers the pharmacological effects of ISL remarking into its mechanism of actions such as how it modulates oxidative stress, inflammatory pathways, glucose metabolism, and cancer growth, demonstrating its pharmacological versatility. The review emphasizes new advances in the field, allowing for more rational development and clinical use of ISL in medicine. However, further research is required to confirm the target-organ toxicity or side-effect investigations.

Periodontitis is a prevalent inflammatory disease that leads to significant periodontal tissue destruction and compromised dental health, with its severity exacerbated in individuals with Diabetes Mellitus (DM). This review explores the complex relationship between mitochondrial dysfunction and periodontitis in diabetic patients. Recent studies indicate that the excessive production of reactive oxygen species (ROS), primarily generated by dysfunctional mitochondrial electron transport chain (ETC) complexes, contributes to oxidative stress (OS) and subsequent periodontal tissue damage. The interplay between impaired mitochondrial biogenesis, apoptosis of periodontal cells, and ROS accumulation highlights a critical area of concern in understanding the pathophysiology of diabetic periodontitis. Furthermore, altered glycemic control due to inflammatory processes associated with periodontitis may perpetuate a cyclical detriment to oral and systemic health. This review aims to highlight the mechanistic roles of mitochondrial dysfunction in the aggravation of periodontitis among diabetic patients, emphasizing further research to identify potential therapeutic targets and improve treatment efficacy for this dual pathology.

An imbalance between oxidative and antioxidant processes in the host can lead to excessive oxidation, a condition known as oxidative stress (OS). Although changes in the hindgut microbiota have been frequently linked to OS, the specific microbial and metabolic underpinnings of this association remain unclear. In this study, we enrolled 81 postpartum Holstein cows and stratified them into high oxidative stress (HOS, n = 9) and low oxidative stress (LOS, n = 9) groups based on the oxidative stress index (OSi). Using a multi-omics approach, we performed 16S rRNA gene sequencing to evaluate microbial diversity, conducted metagenomic analysis to identify functional bacteria, and utilized untargeted metabolomics to profile serum metabolites. Our analyses revealed elevated levels of kynurenine, formyl-5-hydroxykynurenamine, and 5-hydroxyindole-3-acetic acid in LOS dairy cows. Additionally, the LOS cows had a higher abundance of short-chain fatty acids (SCFAs)-producing bacteria, including Bacteroidetes bacterium, Paludibacter propionicigenes, and Phascolarctobacterium succinatutens (P. succinatutens), which were negatively correlated with OSi. To explore the potential role of these bacteria in mitigating OS, we administered P. succinatutens (108 cfu/day for 14 days) to C57BL/6 J mice (n = 10). Oral administration of P. succinatutens significantly increased serum total antioxidant capacity, decreased total oxidants, and reduced OSi in mice. Moreover, this treatment promoted activation of the Nrf2-Keap1 antioxidant pathway, significantly enhancing the enzymatic activities of GSH-Px and SOD, as well as the concentrations of acetate and propionate in the colon. In conclusion, our findings suggest that systemic tryptophan metabolism and disordered SCFAs production are concurrent factors influenced by hindgut microbiota and associated with OS development. Modulating the hindgut microbiota, particularly by introducing specific SCFAs-producing bacteria, could be a promising strategy for combating OS.

In this editorial, we discussed the article published in the recent issue of the World Journal of Diabetes. To understand the effect of mizagliflozin on kidney injury induced by diabetes, we focused on the mechanisms by which high glucose triggers oxidative stress and contributes to kidney injury in diabetes. The high level of unmetabolized glucose reaching the kidney triggers glucose reabsorption by renal tubules, which elevates the cellular glucose level of renal cells. High glucose induces lactate dehydrogenase overexpression and thus shifts glucose metabolism, which causes mitochondrial dysfunction. Mitochondria generate approximately 90% of the reactive oxygen species in cells, whose dysfunction further alters glucose metabolism and enhances reactive oxygen species generation. Oxidative stress stimulates proinflammatory factor production and kidney inflammatory injury. Mizagliflozin decreases glucose reabsorption and thus ameliorates diabetes-induced kidney injury.

Hyperglycemia is characterized by high and uncompensated glucose levels, leading to diabetes mellitus (DM). Helianthus species extracts may have hypoglycemic properties and can be used as a complementary therapy for diabetes and its complications. This review evaluates the effects of extracts from Helianthus species on glycemia reduction in preclinical and clinical studies. Studies that isolated compounds or other associated compounds with the extract did not measure the glycemic profile; review articles and in vitro and ex vivo articles were excluded. The review followed the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) protocols, and the systematic review center for laboratory animal experimentation (SYRCLE) tool was used for preclinical studies risk-of-bias (RoB) assessment. 14 studies, including 12 preclinical and 1 clinical study, were included. A meta-analysis was applied to preclinical studies and showed a significant effect in reducing glycemia and HbA1c levels. Qualitative analysis of the clinical study has also shown a reduction in glycemia. Inulin and chlorogenic acid (CGA) were identified in HelianthustuberosusL. and HelianthusannuusL., respectively, as compounds possibly responsible for these pharmacological effects. Extracts of the Helianthus species have been effective in improving the glycemic profile, making it possible to control DM and minimize its complications.

Our previous studies demonstrated that the enzyme aldose reductase (AR) is activated by its interaction with tubulin, a mechanism which can lead to the emergence of secondary diseases in diabetic patients. We also found that different compounds derived from phenolic acid (CAFs) can prevent this interaction and thus AR activation. Here, we used spectroscopic and bioinformatic techniques to explore the interaction between AR and three CAFs: 3-nitrotyrosine (NTyr), Tyrosine (Tyr), and vanillic acid (Van). The results revealed that the CAFs alter the UV-Vis absorption spectrum of AR and significantly quenchAR fluorescence. These changes suggest the formation of stable AR-CAF complexes. Moreover, a single binding site for the CAFs was identified in AR, to which a single molecule of NTyr and at least two molecules of Tyr or Van appear to bind. NTyr showed the most affinity for interacting with the enzyme, followed by Tyr and Van. Binding occurs through a thermodynamically favorable and exothermic process. It involves van der Waals interactions and the creation of hydrogen bonds between the phenol substituent in the CAFs and the side residues in AR. Molecular docking calculations confirmed NTyr as the compound with the most affinity and revealed the multiple interactions that contribute to this affinity. These findings enhance our understanding of the molecular mechanisms through which different CAFs bind to AR and inhibit its interaction with tubulin. As such, they could pave the way for the design of novel adjunctive treatments that complement conventional antihyperglycemic therapies and mitigate complications associated with diabetes mellitus.

Type 2 diabetes (T2D) accounts for the majority of diabetes incidences and remains a widespread global chronic disorder. Apart from early lifestyle changes, intervention options for T2D are mainly pharmaceutical.

Repetitive transcranial magnetic stimulation (rTMS) has been approved by the FDA as a therapeutic intervention option for major depressive disorders, with further studies also indicating its role in energy metabolism and appetite. Considering its safe and non-invasive properties, we evaluated the effects of rTMS on systemic metabolism using T2D rats.

We observed that rTMS improved glucose tolerance and insulin sensitivity in T2D rats after a 10-day exposure. Improved systemic insulin sensitivity was maintained after a 21-day treatment period, accompanied by modest yet significant weight loss. Circulating serum lipid levels, including those of cholesteryl ester, tryglyceride and ceramides, were also reduced following rTMS application. RNA-seq analyses further revealed a changed expression profile of hepatic genes that are related to sterol production and fatty acid metabolism. Altered expression of hypothalamic genes that are related to appetite regulation, neural activity and ether lipid metabolism were also implicated.

In summary, our data report a positive impact of rTMS on systemic insulin sensitivity and weight management of T2D rats. The underlying mechanisms via which rTMS regulates systemic metabolic parameters partially involve lipid utilization in the periphery as well as central regulation of energy intake and lipid metabolism.

To evaluate the therapeutic potential of the curcumin analog J7 in protecting the liver and regulating glucose and lipid metabolism in rats with type 2 diabetes.

Bioinformatics methods were used to identify signaling pathways linked to diabetic liver disease. Diabetic rats were treated with curcumin, low-dose J7, or high-dose J7, and liver function and fibrosis were assessed through biochemical analyses, histopathology, immunohistochemistry, and ELISA.

J7 administration significantly improved lisver function, reduced fibrosis, and regulated metabolic profiles in diabetic rats. J7 downregulated TGF-β1, NF-κB p65, and BAX, while upregulating BCL-2, showing superior effects to traditional curcumin in reducing TGF-β1 and inhibiting α-SMA expression.

J7 demonstrates potential as a therapeutic agent for managing liver complications in type 2 diabetes, effectively attenuating liver fibrosis and regulating metabolism through the modulation of key signaling pathways and proteins.

Diabetic nephropathy (DN) is one of the most serious and prevalent complications associated with diabetes. Consequently, antidiabetic drugs or foods potentially protecting the kidneys are of significant therapeutic value. Sulforaphene (SFE) is a natural isothiocyanate derived from radish seeds, known for its anti-inflammatory and antioxidant properties. However, no studies have investigated on the ability of SFE to prevent or treat DN. This study established a high-fat diet combined with a streptozotocin-induced type II diabetes mellitus mouse model. We administered SFE treatment to examine its protective effects on renal and intestinal homeostasis in DN mice. After 4 weeks of treatment, SFE (50 mg/kg b.w.) not only reduced blood glucose concentration (20.3 %, P < 0.001), kidney to body weight ratio (26.2 %, P < 0.01), and levels of serum total cholesterol (40.6 %, P < 0.001), triglycerides (38.2 %, P < 0.01), creatinine (36.7 %, P < 0.01), and urea nitrogen (45.0 %, P < 0.001) in DN mice compared to control mice but also increased the kidney superoxide dismutase (72.7 %, P < 0.001), catalase (51.1 %, P < 0.001), and glutathione peroxidase activities (31.6 %, P < 0.01), as well as glutathione levels (39.2 %, P < 0.01) in comparison to DN mice. Furthermore, SFE decreased levels of reactive oxygen species (55.4 %, P < 0.01), 4-hydroxyalkenals (36.9 %, P < 0.001), malondialdehyde (42.6 %, P < 0.001), and 8-hydroxy-deoxyguanosine (26.3 %, P < 0.001), accompanied by a meliorating kidney morphological abnormalities. Notably, a reduction in renal inflammatory factors was also observed in SFE-treated DN mice compared to untreated DN mice, particularly in the C-X-C motif chemokine ligand 8 factors (54.8 %, P < 0.001). Western blotting results indicated that SFE significantly down-regulated the protein expression of TLR4 and MyD88 (1.9, 1.7-fold, P < 0.001). Additionally, SFE improved gut microbiota (GM) dysbiosis and intestinal homeostasis, as evidenced by increased expression of antimicrobial peptides and tight junction proteins in colon tissue. SFE appeared to enhance the proliferation of probiotics, such as Bacteroidota, Lachnospiraceae_NK4A136_group and norank_f__Muribaculaceae, while also decreasing harmful bacteria to a greater extent compared to STZ treatment. These findings suggest that SFE modulates GM and improves intestinal homeostasis, providing a theoretical basis for its use in the treatment of DN.

The endothelium modulates vascular homeostasis owing to a variety of vasoconstrictors and vasodilators. Endothelial dysfunction (ED), characterized by impaired vasodilation, inflammation, and thrombosis, triggers future cardiovascular (CV) diseases. Chronic kidney disease, a state of chronic inflammation caused by oxidative stress, metabolic abnormalities, infection, and uremic toxins damages the endothelium. ED is also associated with a decline in estimated glomerular filtration rate. After kidney transplantation, endothelial functions undergo immediate but partial restoration, promising graft longevity and enhanced CV health. However, the anticipated CV outcomes do not happen due to various transplant-related and unrelated risk factors for ED, culminating in poor CV health and graft survival. ED in kidney transplant recipients is an under-recognized and poorly studied entity. CV diseases are the leading cause of death among kidney transplant candidates with functioning grafts. ED contributes to the pathogenesis of many of the CV diseases. Various biomarkers and vasoreactivity tests are available to study endothelial functions. With an increasing number of transplants happening every year, and improved graft rejection rates due to the availability of effective immunosuppressants, the focus has now shifted to endothelial protection for the prevention, early recognition, and treatment of CV diseases.

To investigate the clinical effect of anti-platelet aggregation drugs combined with Shujin Huoluo Decoction (SJHLD, a decoction for relaxing muscles and activating collaterals) in the treatment of diabetic peripheral vascular disease.

A total of 130 patients with diabetic peripheral vascular disease were retrospectively included in this study and divided into two groups. In the monotherapy group, 65 patients were treated with cilostazol (CTZ) monotherapy; in the combined group, 65 patients were treated with CTZ combined with SJHLD. The treatment efficacy, inflammatory indexes, blood glucose and lipid levels, ultrasound parameters, and hemorheology of the two groups were compared before and after treatment.

Both groups showed significant improvements in walking distance and skin temperature of the toes, with more pronounced changes observed in the combined group (P < 0.05). After treatment, inflammatory markers decreased notably in both groups (P < 0.05). Blood glucose and lipid levels decreased markedly, with a more substantial reduction in lipid levels observed in the combined group (P < 0.05). Lower limb arterial conditions improved markedly in both groups, with greater improvements seen in the combined group (P < 0.05). Additionally, the pulsatile index and blood flow velocity in the ankle-brachial and dorsalis pedis arteries increased markedly in both groups, with the combined group showing a greater improvement (P < 0.05). Hemorheology parameters also decreased significantly in both groups, with the combined group showing a more significant reduction (P < 0.05). The effective treatment rate was significantly higher in the combined group (P < 0.05).

The combination of CTZ and SJHLD significantly improves lower limb function, ultrasound parameters, and blood flow, enhancing treatment efficiency in patients with diabetic peripheral vascular disease. This therapeutic approach offers valuable clinical guidance and warrants consideration for use in diabetic patients.

Background/Objectives: Diabetes mellitus is characterized by a dysregulated glucose metabolism, necessitating frequent and often invasive monitoring techniques for its effective management. Saliva, a non-invasive and readily accessible biofluid, has been proposed as a potential alternative for glycemic monitoring due to its biochemical correlation with blood glucose levels. This scoping review aims to evaluate the evidence regarding the use of salivary glucose as a biomarker to track glycemic changes in diabetic populations. Methods: This study adhered to the Joanna Briggs Institute guidelines and the PRISMA Extension for Scoping Reviews. A literature search was performed across the PubMed, Scopus, and Web of Science databases, supplemented by manual searches. Results: A total of fifty-seven studies were included, representing populations affected by type 1 diabetes (T1D), type 2 diabetes (T2D), and gestational diabetes (GD). The findings indicated consistent positive correlations between the salivary and blood glucose levels in most studies, although there were significant variations in the sensitivity, specificity, and methodological approaches. Salivary glucose showed promise as a complementary biomarker for glycemic monitoring, particularly due to its non-invasive nature. Conclusions: Challenges such as variability in salivary composition, the absence of standardized collection protocols, and the limited availability of portable devices were noted. This review highlights the potential of saliva as an adjunct sample for diabetes management while stressing the need for further research to bridge existing gaps.

The aim of this study was to assess the potential association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and type 2 diabetes mellitus (T2DM) in a middle-aged and elderly Chinese population using data from the China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2015. Methods We used data from CHARLS 2011 as baseline data and follow-up data from 2015. NHHR was used as a continuous and categorical variable, and multivariate logistic regression modeling was used to explore its relationship with T2DM. Three models were developed to adjust for the possible effects of 14 factors on the outcomes. Restricted cubic spline was used to check for possible nonlinear associations, and subgroup and interaction analyses were used to assess differences between groups. Results A total of 7847 subjects were enrolled in the study, of whom 948 (12.1%) were diagnosed with T2DM. The last NHHR quartile group (Q4) presented the highest risk of T2DM (OR, 1.115, 95% CI, 1.088-1.141) after accounting for all covariates. Restricted cubic spline regression modeling revealed a nonlinear relationship between NHHR and T2DM (p for nonlinear = 0.001). The results of the subgroup analyses were consistent across the categories, indicating a significant positive correlation. Interaction analyses revealed significant interactions between NHHR and age, gender and marital status. Conclusion In the middle-aged and elderly population in China, there is a strong correlation between elevated NHHR and increased risk of T2DM onset. The relationship between NHHR and T2DM can be further investigated in the future to provide reference for the development of more accurate prediction models.

Background: Diabetes mellitus (DM) is a major risk factor for the development of periodontal disease and aggravates the severity of periodontal conditions. Matrix metalloproteinases (MMPs) are known to degrade periodontal ligament attachment and bone matrix proteins. Increased expression of CD147 is associated with increased synthesis of several MMPs, being a modulator of MMP expression, including that of MMP-14. The purpose of this study was to quantify and compare the expressions of MMP-14 and CD147 in gingival tissues of patients with and without type 2 diabetes mellitus. Material and Methods: In this histological study, we included 33 subjects with periodontal disease: 16 patients with type 2 DM (test group) and 17 systemically healthy patients (control group). Tissue fragments were processed using an immunohistochemistry technique to determine immunoreactivity (IR) intensity of MMP-14 and CD147. Results: In the group of diabetes patients with periodontitis, 56.2% showed weak positive expressions (+), while 43.8% had intensely positive expressions (+++) of MMP-14. Statistically significant differences between test and control groups (p = 0.004, p = 0.883, and p = 0.002) were found for the membranous IR intensity of MMP-14. In the group of diabetes patients with periodontitis, 56.2% had moderate positive expressions (++) of CD 147, while 43.8% showed intensely positive expressions (+++). Statistically significant differences between the test and control groups were found (p = 0.001, p = 0.002, and p = 0.003) for the membranous IR intensity of CD147. Conclusions: The significantly higher membranous IR intensity for MMP-14 and CD 147 demonstrates the role of these biomarkers in the development of periodontal pathology in diabetes patients. It can be assumed that MMP-14 and CD147 could be further investigated as potential predictive biomarkers.

To explore and validate the association between the oxidative balance and prevalence of diabetic kidney disease (DKD) and mortality in patients with diabetes.

A large and representative sample from the National Health and Nutrition Examination Survey (NHANES) from 2013 to 2016 was analyzed to study the potential association between Oxidative Balance Score (OBS) and prognosis of DKD in adult diabetic patients. Weighted multivariate logistic regression analysis was conducted to examine the relationship between OBS and DKD risk. Subgroup analysis, sensitivity analysis, and mediation effect analysis were conducted to explore the effect of the covariates and assess the robustness of the findings. Mendelian randomization (MR) was employed to evaluate the correlated relationship between mitochondrial reactive oxygen species (ROS) levels and DKD at the genetic level.

The highest OBS quartile showed the most significant negative correlation with DKD compared to the lowest OBS quartile (OR = 0.62, 95% CI 0.41-0.92, P = 0.017). Higher OBS was associated with a reduced risk of DKD (OR = 0.96; 95% CI = 0.93, 0.98; P < 0.001) and mortality (P = 0.021 by log-rank) in diabetic patients. This association remained robust even after excluding individual OBS components. Subgroup analysis revealed the interaction of metabolic syndrome on OBS was significant. Mediation analyses revealed that OBS's effect on DKD was independent of blood uric acid and cholesterol. Restricted cubic spline (RCS) analysis indicated a typical L-shaped relationship between OBS and DKD risk. The physical activity was identified as the core variable predicting DKD risk by two machine learning algorithms. MR showed a potential correlated relationship between ROS and microalbuminuria in DKD.

The high level of oxidative balance score was negatively correlated with the risk of DKD and mortality in diabetic patients.

The molecular mechanisms involved in bone metabolism abnormalities in individuals with type 2 diabetes mellitus (T2DM) are a prominent area of investigation within the life sciences field. Myostatin (MSTN), a member of the TGF-β superfamily, serves as a critical negative regulator of skeletal muscle growth and bone metabolism. Current research on the exercise-mediated regulation of MSTN expression predominantly focuses on its role in skeletal muscle. However, due to the intricate and multifaceted mechanical and biochemical interactions between muscle and bone, the precise mechanisms by which exercise modulates MSTN to enhance bone metabolic disorders in T2DM necessitate additional exploration. The objective of this review is to systematically synthesize and evaluate the role of MSTN in the development of bone metabolism disorders associated with T2DM and elucidate the underlying mechanisms influenced by exercise interventions, aiming to offer novel insights and theoretical recommendations for enhancing bone health through physical activity.

Relevant articles in Chinese and English up to July 2024 were selected using specific search terms and databases (PubMed, CNKI, Web of Science); 147 studies were finally included after evaluation, and the reference lists were checked for other relevant research.

Myostatin's heightened expression in the bone and skeletal muscle of individuals with T2DM can impede various pathways, such as PI3K/AKT/mTOR and Wnt/β-catenin, hindering osteoblast differentiation and bone mineralization. Additionally, it can stimulate osteoclast differentiation and bone resorption capacity by facilitating Smad2-dependent NFATc1 nuclear translocation and PI3K/AKT/AP-1-mediated pro-inflammatory factor expression pathways, thereby contributing to bone metabolism disorders. Physical exercise plays a crucial role in ameliorating bone metabolism abnormalities in individuals with T2DM. Exercise can activate pathways like Wnt/GSK-3β/β-catenin, thereby suppressing myostatin and downstream Smads, CCL20/CCR6, and Nox4 target gene expression, fostering bone formation, inhibiting bone resorption, and enhancing bone metabolism in T2DM.

In the context of T2DM, MSTN has been shown to exacerbate bone metabolic disorders by inhibiting the differentiation of osteoblasts and the process of bone mineralization while simultaneously promoting the differentiation and activity of osteoclasts. Exercise interventions have demonstrated efficacy in downregulating MSTN expression, disrupting its downstream signaling pathways, and enhancing bone metabolism.

Oxidative stress is considered as the root-cause of different pathological conditions. Transition metals, because of their redox-active states, are capable of free radical generation contributing oxidative stress. Hemoglobin and myoglobin are two major heme proteins, involved in oxygen transport and oxygen storage, respectively. Heme prosthetic group of heme proteins is a good reservoir of iron, the most abundant transition metal in human body. Although iron is tightly bound in the heme pocket of these proteins, it is liberated under specific circumstances yielding free ferrous iron. This active iron can react with H2O2, a secondary metabolite, forming hydroxyl radical via Fenton reaction. Hydroxyl radical is the most harmful free radical among all the reactive oxygen species. It causes oxidative stress by damaging lipid membranes, proteins and nucleic acids, activating inflammatory pathways and altering membrane channels, resulting disease conditions. In this review, we have discussed how heme-irons of hemoglobin and myoglobin can promote oxidative stress under different pathophysiological conditions including metabolic syndrome, diabetes, cardiovascular, neurodegenerative and renal diseases. Understanding the association of heme proteins to oxidative stress may be important for knowing the complications as well as therapeutic management of different pathological conditions.

Diabetic retinopathy is the main microvascular complication of diabetes and the first blinding eye disease in the working-age population. Oxidative stress is an important pathogenesis of diabetic retinopathy. Plant metabolites can be divided into two types: primary metabolites and secondary metabolites, secondary metabolites are the main active components and important sources for developing new drugs. It has unique effect in the treatment of diabetic retinopathy. However, the research on the intervention mechanism of plant metabolites in diabetic retinopathy are still relatively shallow, which limit the application of plant metabolites. With the deepening of research, more and more plant metabolites have been reported to play a role in treating diabetic retinopathy through anti-oxidative stress, including polyphenols, polysaccharides, saponins, alkaloids, etc. Therefore, this article reviewed the potential of plant metabolites in the treatment of diabetic retinopathy in the last 10 years and elucidated their mechanism of action. We hope to provide some references for the application of plant metabolites and provide valuable resources for the research and development of new drugs for diabetic retinopathy.

Non-communicable chronic diseases (NCDs) are most commonly characterized by age-related loss of homeostasis and/or by cumulative exposures to environmental factors, which lead to low-grade sustained generation of reactive oxygen species (ROS), chronic inflammation and metabolic imbalance. Nuclear factor erythroid 2-like 2 (NRF2) is a basic leucine-zipper transcription factor that regulates the cellular redox homeostasis. NRF2 controls the expression of more than 250 human genes that share in their regulatory regions a cis-acting enhancer termed the antioxidant response element (ARE). The products of these genes participate in numerous functions including biotransformation and redox homeostasis, lipid and iron metabolism, inflammation, proteostasis, as well as mitochondrial dynamics and energetics. Thus, it is possible that a single pharmacological NRF2 modulator might mitigate the effect of the main hallmarks of NCDs, including oxidative, proteostatic, inflammatory and/or metabolic stress. Research on model organisms has provided tremendous knowledge of the molecular mechanisms by which NRF2 affects NCDs pathogenesis. This review is a comprehensive summary of the most commonly used model organisms of NCDs in which NRF2 has been genetically or pharmacologically modulated, paving the way for drug development to combat NCDs. We discuss the validity and use of these models and identify future challenges.

Diabetes, a metabolic disease associated with an increased health care burden and mortality, is currently on the rise. Both upregulation of the mammalian target of rapamycin (mTOR) and decreased levels of vitamin D (VD) and l-cysteine (LC) have been associated with diabetes. The overactivation of mTOR leads to insulin desensitization and metabolic dysfunction including uncontrolled hyperglycemia. This review summarizes various studies that have shown an inhibitory effect of VD or LC on mTOR activity. Findings from preclinical studies suggest that optimizing the VD and LC status in patients with diabetes can result in mTOR suppression, which has the potential to protect these individuals from microvascular and macrovascular complications while enhancing the regulation of their blood glucose. Given this information, finding ways to suppress mTOR signaling and also increasing VD and LC status is a possible therapeutic approach that might aid patients with diabetes. Future clinical trials are needed to investigate whether VD and LC co-supplementation can successfully downregulate mTOR and can be used as adjuvant therapy in patients with diabetes.

We assessed the efficacy of fasudil hydrochloride, a Rho-kinase inhibitor, as adjunct therapy for enhancing cardiac function, managing blood sugar, and improving quality of life in patients with diabetes who have coronary heart disease (CHD) and who underwent percutaneous coronary intervention (PCI).

We conducted a randomized controlled trial including 100 patients with diabetes and CHD who underwent PCI. Participants were randomly assigned to an experimental group receiving fasudil hydrochloride plus standard therapy or a control group receiving standard therapy alone. Treatment outcomes were evaluated over 3 months, focusing on cardiac function, blood sugar levels, and quality of life across physical, social, activities of daily living, and psychological domains.

The experimental group showed significant improvement in cardiac function and blood sugar control, compared with the control group. Additionally, quality of life scores were markedly higher for the experimental group in all evaluated domains.

Fasudil hydrochloride effectively targets endothelial dysfunction and atherosclerosis, contributing to better cardiac performance and metabolic regulation. These effects translate into improved post-PCI quality of life for patients with diabetes and CHD. As an adjunct to standard PCI therapy, fasudil hydrochloride treatment offers a promising strategy for enhancing clinical outcomes in this high-risk patient population.

High intraocular pressure (HIOP) and high glucose levels are associated with oxidative stress. Although physical exercise protects against oxidative damage, its specific impact on eye health remains unclear. Thus, this study aimed to assess the impact of physical exercise on the oxidative status of whole eyes in male Swiss mice subjected to HIOP model and cafeteria diet (CD). In experiment one, mice were divided into sedentary, aerobic, and strength (four-week physical exercise) groups and subjected to an HIOP/ischemia model. In experiment two, mice were submitted to CD and voluntary physical exercise for 18 weeks, according to the following groups: sedentary control, sedentary CD, exercise control, and exercise CD. Experiment one revealed elevated 2',7'-dichlorodihydrofluorescein (DCFH) levels in aerobic group, which decreased in all groups after ischemia. Nitrite levels were decreased on strength than in sedentary group. The superoxide dismutase (SOD) activity did not change in all treatments. Although catalase (CAT) activity increased in aerobic and strength groups, and after ischemia in all groups. In experiment two, the sedentary CD group presented higher body weight than the other groups. DCFH levels were increased in the exercise control and reduced in the exercise CD compared with the other groups. CAT activity and sulfhydryl groups were decreased, while protein carbonylation was increased in the sedentary CD group compared with the other groups. Thus, these results suggested that physical exercise promoted antioxidant effects on eyes exposed to an HIOP model and CD.

To elucidate the regulatory mechanism of circRNAs in diabetic retinopathy.

Next-generation sequencing (NGS) was employed to identify circRNAs that are abnormally expressed in endothelial progenitor cells (EPCs) under hyperglycemia (HG) conditions. The regulatory mechanism and predicted targets of this circRNA were also studied via bioinformatics analysis, luciferase reporter assays, angiogenic differentiation experiments, flow cytometry, and RT-qPCR.

Circ-astrotactin 1 (circ-Astn1) expression was decreased in EPCs under HG conditions, and circ-Astn1 overexpression inhibited HG-induced endothelial damage. The miR-138-5p and silencing information regulator 2 related enzyme 1 (SIRT1) were identified as circ-Astn1 downstream targets, which were further verified through luciferase reporter assays. SIRT1 silencing or miR-138-5p overexpression reversed the protective effect of circ-Astn1 on HG-induced endothelial cell dysfunction, as evidenced by increased apoptosis, abnormal vascular differentiation, and inflammatory factor secretion. SIRT1 overexpression reversed miR-138-5p-induced endothelial cell dysfunction under HG conditions. In vivo experiments confirmed that circ-Astn1 overexpression promoted skin wound healing through the regulation of SIRT1.

These findings suggest that circ-Astn1 promotes SIRT1 expression by sponging miR-138-5p. Circ-Astn1 overexpression suppresses HG-induced endothelial cell damage via miR-138-5p/SIRT1 axis.

Thymoquinone (TQ), a bioactive compound derived from black cumin seeds, is renowned for its potent anti-obesity and anti-diabetic properties. Due to the stability challenges of TQ, it has predominantly been utilized in oil formulations. This study aimed to enhance the stability of TQ and investigated the impact of consuming insoluble fiber from black cumin seeds on restoring antioxidant function compromised by diabetes and improving hyperglycemia management. We evaluated the restorative effects of a 35-day administration of black cumin seed extract (BCS) on antioxidant function impaired by streptozotocin (STZ)-induced diabetes, alongside structural and functional alterations in the pancreas, liver, and kidneys. The results demonstrated significant improvements in organ weight, particularly in pancreatic tissue. Moreover, BCS administration markedly suppressed the expression of key genes associated with pancreatic dysfunction and damage, including caspase-3, transforming growth factor-beta 1 (TGF-β1), and interleukin-1 beta (IL-1β). Through oral glucose tolerance tests (OGTTs), BCS was found to effectively regulate chronic hyperglycemia and exhibit potential for managing acute hyperglycemia. These findings suggest that BCS not only addresses both glycemic and non-glycemic complications of diabetes but also offers a safe, long-term solution. Consequently, BCS emerges as a promising therapeutic agent for hyperglycemia management, including in prediabetic stages.

A wide range of factors contribute to the overlap of hyperglycemia-acute or chronic-and sarcopenia, as well as their associated adverse consequences, which can lead to impaired physical function, reduced quality of life, and increased mortality risk. These factors include malnutrition (both overnutrition and undernutrition) and low levels of physical activity. Hyperglycemia and sarcopenia are interconnected through a vicious cycle of events that mutually reinforce and worsen each other. To explore this association, our review compiles evidence on: (i) the impact of hyperglycemia on motor and muscle function, with a focus on the mechanisms underlying biochemical changes in the muscles of individuals with or at risk of diabetes and sarcopenia; (ii) the importance of the clinical assessment and control of sarcopenia under hyperglycemic conditions; and (iii) the potential benefits of medical nutrition therapy and increased physical activity as muscle-targeted treatments for this population. Based on the reviewed evidence, we conclude that a regular intake of key functional nutrients, together with structured and supervised resistance and/or aerobic physical activity, can help maintain euglycemia and improve muscle status in all patients with hyperglycemia and sarcopenia.

Type 2 diabetes mellitus (T2DM) is a complex disease that can lead to a variety of life-threatening secondary health conditions. Current treatment strategies primarily revolve around tight glucose control, which is difficult to achieve and often turns out to be dangerous because of possible hypoglycemic events. Numerous long-term studies have demonstrated that complex pathways, including low-grade inflammation due to fluctuating glucose levels, are involved in the progression of the disease and the development of secondary health conditions. Growing clinical evidence supports the effectiveness of using multiple medications, possibly in combination with insulin, to effectively manage T2DM. Despite the huge, largely untapped potential therapeutic benefit of polyphenols, there remains a general skepticism of the practice. However, for any evidence-based clinical intervention, the balance of benefits and risks takes center stage and is governed by biopharmaceutics principles. In this article, we outline the current clinical perspectives on pharmaceutical drug combinations, rationale for early initiation of insulin, and advantages of novel dosage forms to meet the pathophysiological changes of T2DM, emphasizing the need for further clinical studies to substantiate these approaches. We also make the case for traditional medicines and their combinations with pharmaceutical drugs and outline the inherent challenges in doing so, while also providing recommendations for future research and clinical practice. SIGNIFICANCE STATEMENT: Type 2 diabetes is associated with life-threatening secondary health conditions that are often difficult to treat. This review provides an in-depth account of preventing/delaying secondary health conditions through combination therapies and emphasizes the role of effective delivery strategies in realizing the translation of such combinations. This review builds the case for the importance of polyphenols in diabetes, determines the reasons for skepticism, and discusses potential combinations with pharmaceutical drugs.

Oxidative stress plays an important role in the pathogenesis of maternal and fetal complications of diabetic pregnancies.

To assess oxidative stress status in infants of diabetic mothers (IDMs) through measurement of ischemia modified albumin (IMA) and to examine its relation to lipid peroxidation, antioxidant status, essential trace elements, and maternal glycemic control.

This study was conducted on 100 full-term infants; 50 infants were born to diabetic mothers and another 50 age- and sex-matched healthy infants were enrolled as controls. Maternal laboratory investigations included random blood glucose (RBG) and HbA1c. Cord blood RBG, total antioxidant capacity (TAC), malondialdehyde (MDA), IMA, and trace elements (copper [Cu] and zinc [Zn]) were measured.

Cord blood TAC, Cu, and Zn were significantly lower (p < 0.05 for all) while MDA and IMA levels were higher among IDMs compared with the control group (p < 0.001 for both). Maternal HbA1c was negatively correlated to TAC (r = -0.351, p = 0.013) while positively correlated to MDA (r = 0.305, p = 0.031) and IMA (r = 0.755, p < 0.001). IMA was also positively related to maternal RBG (r = 0.493, p < 0.001) while there were negative correlations between IMA and each of TAC (r = -0.491, p < 0.001) and Cu (r = -0.480, p = 0.001).

Oxidative stress is enhanced in IDMs as indicated by increased lipid peroxidation and IMA levels. This is accompanied by decreased antioxidant defense, reflected by decreased TAC, Cu, and Zn levels. Oxidant-antioxidant balance is related to maternal glycemic control. Proper glycemic control among diabetic mothers is mandatory to avoid oxidative stress and its potentially harmful effects on their infants.

Endothelial cells (ECs) are crucial for vascular health, regulating blood flow, nutrient exchange, and modulating immune responses and inflammation. The impairment of these processes causes the endothelial dysfunction (ED) characterized by oxidative stress, inflammation, vascular permeability, and extracellular matrix remodeling. While primary ECs have been widely used to study ED in vitro, their limitations-such as short lifespan and donor variability-pose challenges. In this context, induced iECs derived from induced pluripotent stem cells offer an innovative solution, providing an unlimited source of ECs to explore disease-specific features of ED. Recent advancements in 3D models and microfluidic systems have enhanced the physiological relevance of iEC-based models by better mimicking the vascular microenvironment. These innovations bridge the gap between understanding ED mechanisms and drug developing and screening to prevent or treat ED. This review highlights the current state of iEC technology as a model to study ED in vascular and non-vascular disorders, including diabetes, cardiovascular, and neurodegenerative diseases.

Stroke is a major global health concern, with 12.2 million new cases and 6.6 million deaths reported in 2019, making it the second leading cause of death and third leading cause of disability worldwide. Ischemic stroke, caused by blood vessel occlusion, accounts for 87% of stroke cases and results in neuronal death due to oxygen and nutrient deprivation. The rising global stroke burden is linked to aging populations and increased metabolic risk factors like high blood pressure, obesity, and elevated glucose levels, which promote chronic inflammation. This article explores the intricate molecular and clinical interplay between inflammation and metabolic disorders, emphasizing their role in ischemic stroke development, progression, and outcomes.

Background: Diabetic macular edema (DME) is a leading cause of vision impairment and blindness among diabetic patients, requiring effective diagnostic and monitoring strategies. This systematic review aims to synthesize current knowledge on molecular biomarkers associated with DME, focusing on their potential to improve diagnostic accuracy and disease management. Methods: A comprehensive search was conducted in PubMed, Embase, Medline, and the Cochrane Central Register of Controlled Trials, covering literature from 2004 to 2023. Out of 1074 articles initially identified, 48 relevant articles were included in this systematic review. Results: We found that molecules involved in several cellular processes, such as neuroinflammation, oxidative stress, vascular dysfunction, apoptosis, and cell-to-cell communication, exhibit differential expression profiles in various biological fluids when comparing diabetic individuals with or without macular edema. Conclusions: The study of these molecules could lead to the proper identification of specific biomarkers that may improve the diagnosis, prognosis, and therapeutic management of DME patients.

Oxidative stress (OS) is thought to mediate the processes of glycolipid disorders of a number of metabolic diseases and recent data suggest that OS may be involved in the pathophysiology of hyperlipidemia. The gene expression profiles of hyperlipidemia samples were downloaded from the Gene Expression Omnibus (GEO) database. Oxidative stress-related genes (ORGs) was the intersection of all valid data of discovery dataset and the ORGs in Genecards. The Differentially expressed genes (DEGs) between hyperlipidemia and control samples were obtained via "limma" R package, and differentially expressed oxidative stress-related genes (DEORGs) associated with hyperlipidemia were screened via OS gene sets. Gene Ontology (GO) and Kyoto encyclopaedia of Genes and Genomes (KEGG) enrichment analyses were performed to study the biological function of DEORGs, and protein-protein interaction (PPI) network analysis was conducted to screen hub genes. Then we constructed microRNA (miRNA), transcription factor (TF) and drug component targets network to explain the regulatory mechanism of ORGs in hyperlipidemia. After screening and evaluating we took GSE1010 as the discovery dataset and the GSE13985 as the validation set. There were 395 ORGs and 14 DEORGs retained from the hyperlipidemia. GO and KEGG results showed that DEORGs were mostly related to OS and lipid metabolism. Then, we used miRNA, TF, and drug component targets network to reveal the regulatory mechanism of hub genes. Finally, we verified expression of DEGs and hub gene in validation set. Our study has further confirmed the relationships between OS and hyperlipidemia, providing oxidative stress-related hub genes with possible function analysis and pathways summarized. These molecules might play a crucial role in the progression of hyperlipidemia and serve as potential biomarkers and therapeutic targets, giving us additional insight into the genes and the mechanism linking the OS system and metabolic disorders. We have not only proved hyperlipidemia is associated with OS but also gave foundation and reference for future researches.

Glycation-induced stress (G-iS) is a physiological phenomenon that leads to the formation of advanced glycation end-products, triggering detrimental effects such as oxidative stress, inflammation, and damage to intracellular structures, tissues, and organs. This process is particularly relevant because it has been associated with various human pathologies, including cancer, neurodegenerative diseases, and diabetes. As therapeutic alternatives, coordination compounds with antioxidant activity show promising potential due to their versatility in attenuating oxidative stress and inflammation. Herein, we investigated the antioxidant-related protective potential of a series of complexes: [Cu(II)(BMPA)Cl2] (1), [Fe(III)(BMPA)Cl3] (2), and [Cl(BMPA)MnII-(μ-Cl)2-MnII(BMPA)-(μ-Cl)- MnII(BMPA)(Cl)2]•5H2O (3), all synthesized with the ligand bis-(2-pyridylmethyl)amine (BMPA) in Saccharomyces cerevisiae exposed to G-iS caused by methylglyoxal (MG). Pre- treatment with complexes 1-3 proved highly effective, increasing yeast tolerance to G-iS and attenuating mitochondrial dysfunction. This observed phenotype appears to result from a reduction in intracellular oxidation, lipid peroxidation levels, and glycation. Additionally, an increase in the activity of the antioxidant enzymes superoxide dismutase and catalase was observed following treatment with complexes 1-3. Notably, although complexes 1-3 provided significant protection against oxidative stress induced by H2O2 and menadione, their protective role was more effective against MG-induced glycation stress. Our results indicate that these complexes possess both antiglycation and antioxidant properties, warranting further investigation as potential interventions for mitigating glycation and oxidative stress-related pathologies.

Proliferative diabetic retinopathy (PDR) is the most severe complication of chronic hyperglycaemi stimulates oxidative stress that changes the retinal basement membrane function and provokes neovascularization, macular edema and retinal detachment. But an oxidative-antioxidant biomarker assessment in ocular matrices, such as aqueous humor (AH) and vitreous, might show the oxidative stress (OS) status in the posterior segment. Here, we show a cross-sectional analytical study of 39 patients who had a vitrectomy and assess the levels of different oxidative-antioxidant biomarkers in blood, aqueous and vitreous humor in three groups: diabetes mellitus 2 (DM2) with PDR [DM(+)PDR(+)] (n =13), DM2 without PDR [DM(+)PDR(-)] (n = 13) and non-DM2 non-PDR [DM(-)PDR(-)] as the control group (n = 13). Our finding suggests the presence of oxidative stress in diabetic retinopathy, as evidenced by increased levels of 8-isoprostanes and decreased levels of total antioxidant capacity from stages before the development of diabetic retinopathy. Our results reveal a notable increment in catalase levels in the DM(+)PDR(+) group in blood and vitreous humor. Likewise, we identified that the DM(+)PDR(-) group presents significant levels in 8-IP and SOD in vitreous humor and blood versus aqueous humor. These finding suggest the role of antioxidant enzymes in compensating oxidative stress mechanisms in PDR development.