Patients with impaired glucose metabolism have an increased incidence of post-operative complications. The best marker for glycemic control prior to elective orthopedic surgery remains unclear. We aimed to assess the utility of the hemoglobin glycation index (HGI) in predicting early complications following elective orthopedic surgery.

We retrospectively enrolled 1496 patients who underwent elective orthopedic surgery at Fujian Provincial Hospital in China from Jan 2015 to Jan 2023. Restricted cubic spline (RCS) was used to select the cutoff value of HGI. Propensity score matching (PSM) was performed to reduce confounding bias, and multivariate logistic regression models (with and without adjustment) for complication outcomes were applied to evaluate the odds ratios of HGI.

The U-shaped curve in RCS analysis suggested dividing HGI into three subgroups: the reference interval (-0.76 to -0.10), the lower group (≤ -0.76), and the higher group (> -0.10). The incidence of early complications significantly increased from the lower (12.5%) and higher (12.2%) subgroups to the reference interval (6.9%). Following PSM, total postoperative complications were more common in patients with lower HGI (OR: 3.272, 95% CI: 1.417-7.556), but patients in the higher HGI subgroup had a higher risk of incision complications (OR: 3.735, 95% CI: 1.295-10.769).

After adjusting for HbA1c levels, higher HGI (> -0.1) was a risk factor for incision complications, but not for other complications. The risk of overall postoperative complications in patients with lower HGIs (≤ -0.76) should not be ignored.

Inflammation plays a fundamental role in the development and bidirectional association of di-verse diseases, such as periodontitis and type 2 diabetes mellitus (T2DM), which generates important clinical complications, where chronic exposure to high levels of blood glucose affects the repair process of periodontal tissues. Likewise, it has been observed that comorbidity, between these two diseases, influences the development of the COVID-19 disease towards a more severe course. However, there is currently very little scientific evidence on the relationship between periodontitis, T2DM and COVID-19 disease. This narrative review aims to provide an understanding of the current and most relevant aspects of the relationship between periodontitis, T2DM and COVID-19 disease. A narrative review was performed through a systematic search of published studies, without date restrictions, indexed in the electronic databases of PubMed, for the inclusion of articles in English, and LILACS for the inclusion of articles in Spanish. This review included different articles, which addressed the most important aspects to present a current perspective on the relationship and influence between periodontitis, T2DM and COVID-19 disease. Comorbidity between periodontitis and T2DM represents a greater risk of developing a more severe course of COVID-19 disease, because these three diseases share three important axes: a clinicopathological axis; an axis associated with glycemia, and an immunological axis associated with inflammation.

Patients with diabetes are considered to be at high surgical risk due to the potential occurrence of cardiovascular and diabetes-related complications. Limited research exists on the cardiovascular risk profiles of patients with prediabetes and undiagnosed diabetes in noncardiac surgery. In this population-based cohort study, we investigated different glycated hemoglobin levels and their associated postoperative cardiovascular risks.

In this perioperative cohort study, participants were categorized into four groups: nondiabetes, prediabetes, undiagnosed diabetes, and diagnosed diabetes. The primary endpoint was the occurrence of major adverse cardiovascular events (MACE) at 30 days postoperatively, with secondary outcomes assessed at 90 days. The association between various groups and postoperative MACE was evaluated using Cox proportional hazards models and Kaplan-Meier curves. Subgroup analyses and sensitivity analyses were also performed.

We enrolled 13 207 eligible patients undergoing noncardiac surgeries, among whom 3841 (29.08%) had prediabetes and 1521 (11.52%) had undiagnosed diabetes. In the 30-day postoperative period, the prediabetes group (hazard ratio [HR] [95% CI]: 1.70 [1.15, 2.52]), undiagnosed diabetes group (HR [95% CI]: 2.36 [1.15, 3.68]), and diagnosed diabetes group (HR [95% CI]: 2.33 [1.54, 3.53]) exhibited increased risks of MACE compared to the nondiabetes group. Similar findings were observed for the 90-day postoperative MACE. Further subgroup analysis revealed a significant interaction between sex and states of glycemic regulation (P for interaction < 0.005).

In this cohort, a notable proportion of patients with prediabetes or undiagnosed diabetes were found to be undergoing noncardiac surgeries. They were associated with an increased risk of developing postoperative MACE.

Postprandial metabolic disturbances are exacerbated in type 2 diabetes (T2D). Cocoa and carob, despite showing promising effects on these alterations in preclinical studies, have not yet been jointly tested in a clinical trial. Therefore, this acute, randomised, controlled, crossover nutritional trial evaluated the postprandial effects of a cocoa-carob blend (CCB) in participants with T2D (n = 20) and overweight/obesity. The subjects followed three treatments: hypercaloric breakfast (high-sugar and high-saturated fat, 900 kcal) as the control (treatment C); the same breakfast together with 10 g of the CCB, with 5.6 g of dietary fibre and 1.6 g of total polyphenols (treatment A); and the same breakfast after consuming the CCB (10 g) the night before (treatment B). Various analyses were performed, including the determination of the clinical markers of T2D (fasting and postprandial glucose and insulin, GLP-1, and glycaemic profile), satiety evaluation, analysis of exosomal miRNA expression and ex vivo determination of inflammation modulation. No effect on glucose homeostasis (glucose, insulin, and GLP-1) was found in the study population. However, eight exosomal miRNAs were found to be significantly modified owing to CCB supplementation compared with treatment C, with three of them (miR-20A-5p, miR-23A-3p, and miR-17-5p) associated with an improvement in insulin sensitivity. Furthermore, the CCB caused a decrease in hunger feelings (0-120 min), as assessed by the visual analogue scale (VAS). Finally, treatment A caused a significant decrease in the glucose increment within 0-30 min of treatment in subjects with overweight. No significant modifications were found in the other assessed parameters. The acute intake of the CCB by subjects with T2D showed modest although significant results, which need to be validated in a long-term randomised controlled trial.

Objective: This study investigates the in-vitro and in-vivo antioxidant capacities showed by Phlogacanthus thyrsiflorus Nees. (P. thyrsiflorus) in alloxan-administered diabetic mice.

Materials and Methods: The screening of phytochemical of methanolic flower extract (MFE), Gas Chromatography Mass Spectrometry (GC-MS) profiling was utilized to identify bioactive compounds. In-vitro antioxidant studies were performed. Acute toxicity was evaluated in mice. Glucose Transporter type 4 (GLUT4) protein expression and antioxidant enzyme activities were assessed. Histopathological examination of heart tissue was performed.

Results: GC-MS analysis revealed the presence of various bioactive compounds consisting of antioxidant, anti-inflammatory activities. The results also showed a noteworthy increase in in-vitro and in-vivo antioxidant enzymes activities. Moreover, MFE suppress hyperglycaemia by upregulating GLUT4 protein expression. In histological study MFE was found to restore cellular alterations in diabetic tissue.

Discussion and Conclusion: It is inferred from the study that MFE of P. thyrsiflorus can exert a protective effect by suppressing hyperglycaemia and modulating oxidative stress in alloxan-administered diabetic mice.

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 prognostic nutritional index (PNI), an indicator of nutritional status, has been linked to various diabetic complications. However, its relationship with diabetic peripheral neuropathy (DPN) remains unclear. This study aimed to explore the association between PNI and DPN using machine learning (ML) approaches.

A total of 625 patients with type 2 diabetes (T2D) were enrolled, with 282 diagnosed with DPN. PNI was calculated based on serum albumin and lymphocyte count. Random forest (RF) and eXtreme Gradient Boosting (XGBoost) models were developed to predict DPN using clinical and biochemical data. SHapley Additive exPlanations (SHAP) were applied to determine feature importance. Multivariate logistic regression was used to evaluate the relationship between PNI quartile and DPN risks.

Both RF and XGBoost models exhibited strong performance. The RF model achieved a recall of 78.4%, specificity of 87.8%, and accuracy of 84.0%, while the XGBoost model showed a recall of 77.4%, specificity of 92.1%, and accuracy of 84.8%. SHAP analysis identified lower PNI as a key factor for DPN. Multivariate logistic regression revealed that patients in the lowest PNI quartile had a significantly higher DPN risk compared to those in the highest quartile (OR: 3.271, 95% CI: 1.782-6.006, P < 0.001). Additionally, lower PNI levels were associated with impaired peripheral nerve function, including reduced motor and sensory nerve conduction velocity and action potential amplitudes.

Lower PNI levels were associated with increased DPN risk and poorer nerve function, highlighting the importance of nutritional status in DPN management. Further longitudinal studies are needed to confirm these findings.

Background/Objectives: Radiological imaging is crucial in intensive care settings, particularly for the differential diagnosis of fever and sepsis. Computed tomography (CT) is the preferred method for detecting infectious foci in critically ill ICU patients. Methods: This study prospectively analyzed non-ECG-gated chest and abdominal CT scans from ICU patients to assess CT's diagnostic utility. Data from prior imaging modalities (CT, radiography, MRI, ultrasound), microbiological assays (blood cultures, bronchoalveolar lavage, urinalysis), and enzymatic profiles (transaminases, pancreatic enzymes) were included. The predictive value of clinical and laboratory parameters was evaluated via correlation analysis. Results: A total of 112 patients were evaluated, with 99 exhibiting 147 inflammatory foci (92 thoracic, 55 abdominal). Definitive diagnoses were made in 58.5% of cases, while 41.5% remained classified as possible. Prior diagnostic procedures identified inflammatory origins in 57.1% of cases. Fewer CT-detected foci were observed in patients with bronchial asthma or type 2 diabetes mellitus (p = 0.049 and p = 0.006). Conclusions: CT imaging plays a central role in identifying infectious foci in ICU patients with unexplained syndromes, particularly in the thoracic region. CT scanning is recommended for sepsis management when other diagnostic evidence is lacking. Conditions such as bronchial asthma or diabetes mellitus may prompt earlier suspicion of infectious foci due to elevated inflammatory markers.

Type 2 diabetes mellitus (T2DM) often leads to vascular complications, such as albuminuria. The role of insulin autoantibodies (IAA) and their interaction with D-dimer in this context remains unclear.

To investigate the characteristics of IAA and its effect on albuminuria in T2DM patients.

We retrospectively analyzed clinical data from 115 T2DM patients with positive IAA induced by exogenous insulin, and 115 age- and sex-matched IAA-negative T2DM patients as controls. Propensity scores were calculated using multivariate logistic regression. Key variables were selected using the least absolute shrinkage and selection operator (LASSO) algorithm. We constructed a prediction model and analyzed the association between IAA and albuminuria based on demographic and laboratory parameters.

The IAA-positive group had significantly higher D-dimer levels [0.30 (0.19-0.55) mg/L vs 0.21 (0.19-0.33) mg/L, P = 0.008] and plasma insulin levels [39.1 (12.0-102.7) μU/mL vs 9.8 (5.5-17.6) μU/mL, P < 0.001] compared to the IAA-negative group. Increases in the insulin dose per weight ratio, diabetes duration, and urinary albumin-to-creatinine ratio (UACR) were observed but did not reach statistical significance. The LASSO model identified plasma insulin and D-dimer as key factors with larger coefficients. D-dimer was significantly associated with UACR in the total and IAA-positive groups but not in the IAA-negative group. The odds ratio for D-dimer elevation (> 0.5 g/L) was 2.88 (95% confidence interval: 1.17-7.07) in the IAA-positive group (P interaction < 0.05).

D-dimer elevation is an independent risk factor for abnormal albuminuria and interacts with IAA in the development of abnormal albuminuria in T2DM patients.

Protease-activated receptor 2 (PAR2) is a seven-transmembrane, G-protein-coupled receptor that is activated by coagulation proteases such as factor VIIa and factor Xa and other serine proteases. It is a potential therapeutic target for kidney injury, as it enhances inflammatory and fibrotic responses via the nuclear factor-kappa B and mitogen-activated protein kinase cascades. The body of knowledge regarding the role of PAR2 in kidney disease is currently growing, and its role in various kidney disease models, such as acute kidney injury, renal fibrosis, diabetic kidney disease, aging, and thrombotic microangiopathy, has been reported. Here, we review the literature to better understand the various aspects of PAR2 in kidney disease.

To investigate the potential impact of preoperative semaglutide use (the active agent in Ozempic and Wegovy) on 90-day postoperative outcomes and 2-year rotator cuff retear after arthroscopic rotator cuff repair (ARCR) in patients with type II diabetes mellitus (T2DM).

Patients with T2DM undergoing primary ARCR were identified from the PearlDiver database using administrative billing codes. Exclusion criteria included patients <18 years old; previous RCR; concurrent nonrotator cuff-related arthroscopic shoulder procedures; any traumatic, neoplastic, or infectious diagnoses within 90 days before surgery; and <90-days follow-up. Patients with T2DM using semaglutide within 1 year of ARCR ([+]semaglutide) were matched 1:4 with patients with T2DM who did not ([-]semaglutide) by age, sex, Elixhauser Comorbidity Index, diabetes complications, obesity, tobacco, insulin, and metformin use. Occurrence of any adverse events (AAE), severe adverse events (SAE), and minor adverse events (MAE) within 90 days were compared by multivariable logistic regression. The 2-year retear was assessed by Kaplan-Meier survival analysis and compared by log-rank test.

There were 1,094 ARCR (+)semaglutide and 4,110 ARCR (-)semaglutide patients meeting inclusion criteria after matching. The incidence of AAE for the ARCR (-)semaglutide versus ARCR (+)semaglutide patients was 27.4% versus 11.0%, SAE was 10.5% versus 3.5%, and MAE was 22.0% versus 8.5%, respectively (P < .001 for all). ARCR (-)semaglutide patients had a greater odds ratio of AAE (3.65, P < .001) and SAE (3.62, P < .001), including surgical-site infection (2.22, P = .049), venous thromboembolism (3.10, P < .001), sepsis (3.87, P < .001), and cardiac events (3.96, P < .001), as well as greater odds of MAE (3.59, P < .001), including urinary tract infection (3.27), pneumonia (3.88), acute kidney injury (3.91), and emergency department visits (2.51) (P < .001 for all). In addition, (-)semaglutide patients revealed greater 2-year retear vs (+)semaglutide patients (18.3% vs 12.5%, respectively) (P < .001).

Preoperative semaglutide use for patients with T2DM undergoing ARCR was associated with decreased odds of minor and serious 90-day adverse events and lower 2-year rotator cuff retear.

Level III, retrospective comparative study.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder that significantly increases the risk of cardiovascular disease, which is the leading cause of morbidity and mortality among diabetic patients. A central pathophysiological mechanism linking T2DM to cardiovascular complications is oxidative stress, defined as an imbalance between reactive oxygen species (ROS) production and the body's antioxidant defenses. Hyperglycemia in T2DM promotes oxidative stress through various pathways, including the formation of advanced glycation end products, the activation of protein kinase C, mitochondrial dysfunction, and the polyol pathway. These processes enhance ROS generation, leading to endothelial dysfunction, vascular inflammation, and the exacerbation of cardiovascular damage. Additionally, oxidative stress disrupts nitric oxide signaling, impairing vasodilation and promoting vasoconstriction, which contributes to vascular complications. This review explores the molecular mechanisms by which oxidative stress contributes to the pathogenesis of cardiovascular disease in T2DM. It also examines the potential of lifestyle modifications, such as dietary changes and physical activity, in reducing oxidative stress and mitigating cardiovascular risks in this high-risk population. Understanding these mechanisms is critical for developing targeted therapeutic strategies to improve cardiovascular outcomes in diabetic patients.

The impact of macrovascular and microvascular complications, the common vascular complications of type 2 diabetes, on long-term mortality has been well evaluated, but the impact of different complications of newly diagnosed type 2 diabetes (diagnosed within the past 2 years) on long-term mortality has not been reported. We aimed to investigate the relationship between all-cause mortality and vascular complications in U.S. adults (aged ≥ 20 years) with newly diagnosed type 2 diabetes.

We used data from the 1999-2018 National Health and Nutritional Examination Surveys (NHANES). Cox proportional hazard models was used to assess hazard ratios (HR) and 95% confidence intervals for all-cause mortality.

A total of 928 participants were enrolled in this study. At a mean follow-up of 10.8 years, 181 individuals died. In the fully adjusted model, the hazard ratio (HR) (95% confidence interval [CI]) of all-cause mortality for individuals with any single complication compared with those with newly diagnosed type 2 diabetes without complications was 2.24 (1.37, 3.69), and for individuals with two or more complications was 5.34 (3.01, 9.46).Co-existing Chronic kidney disease (CKD) and diabetic retinopathy (DR) at baseline were associated with the highest risk of death (HR 6.07[2.92-12.62]), followed by CKD and cardiovascular disease (CVD) (HR 4.98[2.79-8.89]) and CVD and DR (HR 4.58 [1.98-10.57]).

The presence of single and combined diabetes complications exerts a long-term synergistic adverse impact on overall mortality in newly diagnosed U.S. adults with type 2 diabetes, underscoring the importance of comprehensive complication screening to enhance risk stratification and treatment.

Recent studies have found that a link between people with type 1 diabetes mellitus (T1DM) are at higher risk of morbidity as well as mortality from COVID-19 infection, indicating a need for vaccination. T1DM appears to impair innate and adaptive immunity. The overabundance of pro-inflammatory cytokines produced in COVID-19 illness that is severe and potentially fatal is known as a "cytokine storm." Numerous cohorts have revealed chronic inflammation as a key risk factor for unfavorable COVID-19 outcomes. TNF-α, interleukin (IL)-1a, IL-1, IL-2, IL-6, and other cytokines were found in higher concentrations in patients with T1DM. Even more importantly, oxidative stress contributes significantly to the severity and course of COVID- 19's significant role in the progression and severity of COVID-19 diseases. Severe glucose excursions, a defining characteristic of type 1 diabetes, are widely recognized for their potent role as mediating agents of oxidative stress via several routes, such as heightened production of advanced glycation end products (AGEs) and activation of protein kinase C (PKC). Furthermore, persistent endothelial dysfunction and hypercoagulation found in T1DM may impair microcirculation and endothelium, which could result in the development of various organ failure and acute breathing syndrome.

This study investigates the relationship between the albumin-to-creatinine ratio and diabetic retinopathy (DR) in US adults using NHANES data from 2009 to 2016. This study assesses the predictive efficacy of the urinary serum albumin-to-creatinine ratio (UACR/SACR Ratio) against traditional biomarkers such as the serum albumin-to-creatinine ratio (SACR) and urinary albumin-to-creatinine ratio (UACR) for evaluating DR risk. Additionally, the study explores the potential of these biomarkers, both individually and in combination with HbA1c, for early detection and risk stratification of DR.

This cross-sectional study analysed data from 2594 diabetic adults in the National Health and Nutrition Examination Survey (NHANES 2009-2016). Multivariate logistic regression models, adjusted for demographic (sex, age, race and education) and clinical factors (WBC, PLT, RDW, HbA1c, HBP and CHD), examined the associations between biomarkers and DR. Biomarkers were analysed both continuously and in quartiles to assess dose-response relationships. Receiver operating characteristic (ROC) curve analysis evaluated the predictive accuracy of individual biomarkers and combined models.

Elevated SACR levels were inversely related to DR risk, while UACR showed a positive correlation. The UACR/SACR ratio demonstrated superior predictive capability for DR compared to SACR and UACR alone. The most accurate predictive model combined SACR, UACR, UACR/SACR ratio and HbA1c (AUC = 0.614), highlighting DR development complexity. Subgroup analyses revealed stronger associations in participants aged < 60 years and those with hypertension (both p < 0.05), with more pronounced effects observed in males and Mexican Americans, while lifestyle factors showed no significant modifying effect.

The UACR/SACR Ratio emerged as a potentially superior DR predictor, particularly in younger patients and those with hypertension, suggesting its utility in enhancing early detection and risk stratification. Comprehensive evaluation of renal function and glycaemic control biomarkers, considering age- and comorbidity-specific patterns, could improve DR risk prediction and management. Future longitudinal studies should validate these findings, particularly in identified high-risk subgroups, and investigate underlying mechanisms, potentially advancing personalised DR prediction and management strategies.

Background: Unprovoked venous thromboembolism is a poorly understood entity. Clinical risk factors and future outcomes are not well recognized in this subgroup of patients. Various pathogenic mechanisms like inflammation and athero-thrombosis have been put forth but remain investigative. Our study aimed to determine the clinical profile and predictors of mortality in patients with idiopathic pulmonary embolism. Methods: Our single centre observational study included 510 consecutive patients with symptomatic unprovoked venous thromboembolism. Pulmonary embolism (PE) patients were initially categorized based on the presence or absence of deep vein thrombosis (DVT). Subsequently, the patients were further sub-grouped according to mortality, and the association between clinical parameters and death was evaluated through regression analysis. Results: The in-hospital mortality of patients with unprovoked pulmonary embolism was 15.9% and 25.76% at three year follow up. Significantly higher number of patients with diabetes, hypertension, dyslipidaemia, lower TAPSE (tricuspid annular plane systolic excursion) and PASP (pulmonary arterial systolic pressure) were found in mortality patients compared to survivor patients. On regression analysis we found significant association of higher odds of age OR = 1.1 (1.05-1.23), diabetes OR = 2.47 (1.28-4.79), hypertension OR = 2.25 (1.19-4.26) and lower odds of thrombolysis OR = 0.38 (0.11-0.59) with mortality. On Kaplan Meier survival analysis, the log value of <0.05 showed significantly higher mortality in patients who were not thrombolyzed. Conclusion: Various short and long-term predictors of mortality exist for pulmonary embolism. Cardiovascular risk factors play a mediating role in venous thromboembolism and also serve as predictors for long-term mortality. Therefore, modifying these risk factors can potentially result in a reduction in long-term mortality.

Diabetes is a complex condition with a rising global incidence, and its impact is equally evident in pediatric practice. Regardless of whether we are dealing with type 1 or type 2 diabetes, the development of complications following the onset of the disease is inevitable. Consequently, contemporary medicine must concentrate on understanding the pathophysiological mechanisms driving systemic decline and on finding ways to address them. We are particularly interested in the effects of oxidative stress on target cells and organs, such as pancreatic islets, the retina, kidneys, and the neurological or cardiovascular systems. Our goal is to explore, using the latest data from international scientific databases, the relationship between oxidative stress and the development or persistence of systemic damage associated with diabetes in children. Additionally, we highlight the beneficial roles of antioxidants such as vitamins, minerals, polyphenols, and other bioactive molecules; in mitigating the pathogenic cascade, detailing how they intervene and their bioactive properties. As a result, our study provides a comprehensive exploration of the key aspects of the oxidative stress-antioxidants-pediatric diabetes triad, expanding understanding of their significance in various systemic diseases.

Patients with diabetes commonly experience an aberrant production of free radicals and weakened antioxidative defenses, making them highly susceptible to oxidative stress development. This, in turn, can induce and promote diabetic complications. Therefore, utilizing antidiabetic agents with antioxidative properties can offer dual benefits by addressing hyperglycemia and reducing oxidative damage. Semaglutide, a recently approved oral form of glucagon-like peptide-1 (GLP-1) analogues, has shown potent antidiabetic effects. Additionally, recent studies have suggested that it possesses antioxidative properties. However, the exact effects and the molecular pathways involved are not well understood. In this review, we present the latest findings on the antioxidative impacts of semaglutide and draw conclusions about the mechanisms involved.

Diabetes is an important chronic disease that can lead to various negative consequences and complications. In recent years, several new alternative treatments have been developed to improve diabetes. Carvacrol found in essential oils of numerous plant species and has crucial potential effects on diabetes. The anti-diabetic effects of carvacrol have also been comprehensively studied in diabetic animal and cell models. In addition, carvacrol could improve diabetes through affecting diabetes-related enzymes, insulin resistance, insulin sensitivity, glucose uptake, anti-oxidant, and anti-inflammatory mechanisms. The use of carvacrol alone or in combination with anti-diabetic therapies could show a significant potential effect in the treatment of diabetes. This review contributes an overview of the effect of carvacrol in diabetes and anti-diabetic mechanisms.

Diabetes mellitus (DM) and its complications seriously threaten human life and health. Rhaponticum carthamoides (Willd.) Iljin (RC) is widely used to treat cardiovascular diseases. Previous studies reported that RC reduces blood glucose levels in rats with type 1 DM. However, the effects of RC on type 2 diabetes and vascular complications, as well as its related active components and underlying mechanisms, remain unclear.

This study aimed to investigate the effects of RC on endothelial dysfunction and the inflammatory response in type 2 DM mice and to explore its underlying mechanism and active ingredients.

Male C57BL/6J mice were used to establish a type 2 DM mouse model. After 12 weeks of oral administration of RC extract (60, 120, and 240 mg/kg) to mice, blood glucose and lipid levels were assessed. The morphological structures of the liver and kidney tissues were observed using hematoxylin and eosin (HE) staining, and their functions were evaluated by detecting relevant biochemical indicators in the serum. Then, aorta morphology was observed via HE staining. In addition, serum levels of markers of endothelial function and inflammatory factors were detected, and the expression of inflammatory factors and the phosphorylation levels of key proteins in the aorta were examined. Furthermore, prediction and enrichment analyses of potential targets of RC acting on diabetic vascular lesions were performed on the basis of pharmacophore matching using various databases. Then, the expression, localization and phosphorylation levels of potential targets in the aortas of DM mice treated with RC were assessed using Western blotting, immunofluorescence, and RT‒PCR. Finally, the active components of RC were identified through virtual screening, and their ability to improve endothelial cell dysfunction was verified.

RC reduced blood glucose levels and serum lipid levels of total triglyceride (TG), total cholesterol (TC), and low density lipoprotein cholesterol (LDL-c), increased high density lipoprotein cholesterol (HDL-c) levels, and improved liver and kidney function in type 2 DM mice. RC decreased endothelial cell shedding in the aortas of type 2 DM mice, increased serum nitric oxide (NO) and nitric oxide synthase (NOS) levels, and reduced soluble cluster of differentiation 40 ligand (sCD40L), tumor necrosis factor α (TNF-α), and interleukin-1β (IL-1β) levels. Further findings indicated that RC reduced the expression of aortic inflammatory factors, namely, CD40, CD40L, IL-1β, and interleukin-6 (IL-6), and increased endothelial NOS (eNOS) phosphorylation levels. Sirtuin 6 (SIRT6), protein kinase B (AKT), and eNOS were predicted to be key node targets of RC acting on DM vascular lesions, and it was confirmed that RC increased SIRT6 expression and AKT phosphorylation levels in aortic endothelial cells. 20-Hydroxyecdysone (20E), daucosterol (Dau), euscaphic acid (Eus), and syringin (Syr) were identified as active components of RC. These components protect against TNF-α-induced human umbilical vein endothelial cell (HUVEC) damage and decrease the release of lactate dehydrogenase (LDH) and IL-1β and increased the release of NO in TNF-α-induced HUVECs in a dose-dependent manner.

RC reduced blood glucose and lipid levels in mice with type 2 DM and protected liver and kidney function. RC promotes SIRT6 expression in endothelial cells; upregulates the NO/NOS system by increasing AKT/eNOS phosphorylation levels to regulate vascular tone factors; and reduces the levels of inflammatory factors such as CD40, TNF-α, and IL-1β to inhibit endothelial inflammatory responses. Based on these mechanisms, RC improves endothelial dysfunction.

Type 2 diabetes (T2D) is characterised by insulin resistance and leads to hyperglycaemia. Its prevalence and associated complications continue to rise exponentially, despite the existence of pharmaceutical drugs, and this has prompted research into exploring safer herbal remedies. Portulaca oleracea (purslane) has been investigated in animal and clinical trials to explore its effects on diabetes, yielding conflicting results. This study aimed to evaluate the effects of purslane on inflammation and oxidative stress in diabetes mellitus. We conducted a comprehensive literature search on Scopus PubMed, and through a manual bibliographical search to find relevant studies from inception to 13 September 2024. The search terms included purslane, portulaca oleracea, and type 2 diabetes mellitus. Of the 38 retrieved studies, 12 were considered relevant and underwent critical review. Evidence from rodent studies showed decreased inflammatory markers such as interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), nuclear factor kappa-beta (NF-κβ), and C-reactive (CRP), while interleukin-10 (IL-10) was increased after intervention with purslane. The markers of oxidative stress such as superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx), and total antioxidant capacity (TAC) levels increased, thiobarbituric acid reactive substances (TBARS), reactive oxygen species (ROS) and malondialdehyde (MDA) decreased. Notably, the evidence from clinical trials showed a significant reduction in NF-κβ and CRP after purslane treatment; however, no effect was observed on MDA and TAC. The evidence gathered in this study suggests that purslane exerts anti-inflammatory properties by downregulating NF-κβ, thus suppressing the production of associated pro-inflammatory cytokines. Therefore, purslane may be used as an antioxidant and inflammatory agent for diabetes. However, further clinical evidence with a broader population is required to validate the therapeutic properties of purslane in diabetes.

Vascular calcification is a major contributor to cardiovascular disease, especially diabetes, where it exacerbates morbidity and mortality. Although pyrophosphate is a recognized natural inhibitor of vascular calcification, there have been no prior studies examining its specific deficiency in diabetic conditions. This study is the first to analyze the direct link between elevated glucose levels and disruptions in extracellular pyrophosphate metabolism.

Rat aortic smooth muscle cells, streptozotocin (STZ)-induced diabetic rats, and diabetic human aortic smooth muscle cells were used to assess the effects of elevated glucose levels on pyrophosphate metabolism and vascular calcification. The techniques used include extracellular pyrophosphate metabolism assays, thin-layer chromatography, phosphate-induced calcification assays, BrdU incorporation for DNA synthesis, aortic smooth muscle cell viability and proliferation assays, and quantitative PCR for enzyme expression analysis. Additionally, extracellular pyrophosphate metabolism was examined through the use of radiolabeled isotopes to track ATP and pyrophosphate transformations.

Elevated glucose led to a significant reduction in extracellular pyrophosphate across all diabetic models. This metabolic disruption was marked by notable downregulation of both the expression and activity of ectonucleotide pyrophosphatase/phosphodiesterase 1, a key enzyme that converts ATP to pyrophosphate. We also observed an upregulation of ectonucleoside triphosphate diphosphohydrolase 1, which preferentially hydrolyzes ATP to inorganic phosphate rather than pyrophosphate. Moreover, tissue-nonspecific alkaline phosphatase activity was markedly elevated across all diabetic models. This shift in enzyme activity significantly reduced the pyrophosphate/phosphate ratio. In addition, we noted a marked downregulation of matrix Gla protein, another inhibitor of vascular calcification. The impaired pyrophosphate metabolism was further corroborated by calcification experiments across all three diabetic models, which demonstrated an increased propensity for vascular calcification.

This study demonstrated that diabetes-induced high glucose disrupts extracellular pyrophosphate metabolism, compromising its protective role against vascular calcification. These findings identify pyrophosphate deficiency as a potential mechanism in diabetic vascular calcification, highlighting a new therapeutic target. Strategies aimed at restoring or enhancing pyrophosphate levels may offer significant potential in mitigating cardiovascular complications in diabetic patients, meriting further investigation.

Medicinal plants are a rich source of bioactive compounds that possess pharmacological properties for preventing and treating inflammation-related diseases. Essential oils is a chemical class that contains many bioactive compounds, such as eugenol, which is capable of inhibiting or modulating the inflammatory response. This natural product emerges as a compound that promotes various biological activities, including antioxidant activity, which makes it useful in the food industry. Recently, its pharmacological applications have also been highlighted. So, this review aims to update and discuss the most recent findings on the anti-inflammatory and antioxidant activities of eugenol, along with its mechanisms of action and therapeutic potential for treating inflammation and oxidative imbalance conditions.

Gestational diabetes mellitus (GDM) is the first spontaneous hyperglycemia during pregnancy. Early diagnosis and intervention are important for the management of the disease. This study compared and analyzed the proteins of total plasma exosomes (T-EXO) and placental-derived exosomes (PLAP-EXO) in pregnant women who subsequently developed GDM (12-16 weeks), GDM patients (24-28 weeks) and their corresponding controls to investigate the pathogenesis and biomarkers of GDM associated with exosomes. The exosomal proteins were extracted and studied by proteomics approach, then bioinformatics analysis was applied to the differentially expressed proteins (DEPs) between the groups. At 12-16 and 24-28 weeks of gestation, 36 and 21 DEPs were identified in T-EXO, while 34 and 20 DEPs were identified in PLAP-EXO between GDM and controls, respectively. These proteins are mainly involved in complement pathways, immunity, inflammation, coagulation and other pathways, most of them have been previously reported as blood or exosomal proteins associated with GDM. The findings suggest that the development of GDM is a progressive process and that early changes promote the development of the disease. Maternal and placental factors play a key role in the pathogenesis of GDM. These proteins especially Hub proteins have the potential to become predictive and diagnostic biomarkers for GDM.

Type 2 diabetes (T2D) is a disease characterized by heterogeneously progressive loss of islet β cell insulin secretion usually occurring after the presence of insulin resistance (IR) and it is one component of metabolic syndrome (MS), and we named it metabolic dysfunction syndrome (MDS). The pathogenesis of T2D is not fully understood, with IR and β cell dysfunction playing central roles in its pathophysiology. Dyslipidemia, hyperglycemia, along with other metabolic disorders, results in IR and/or islet β cell dysfunction via some shared pathways, such as inflammation, endoplasmic reticulum stress (ERS), oxidative stress, and ectopic lipid deposition. There is currently no cure for T2D, but it can be prevented or in remission by lifestyle intervention and/or some medication. If prevention fails, holistic and personalized management should be taken as soon as possible through timely detection and diagnosis, considering target organ protection, comorbidities, treatment goals, and other factors in reality. T2D is often accompanied by other components of MDS, such as preobesity/obesity, metabolic dysfunction associated steatotic liver disease, dyslipidemia, which usually occurs before it, and they are considered as the upstream diseases of T2D. It is more appropriate to call "diabetic complications" as "MDS-related target organ damage (TOD)", since their development involves not only hyperglycemia but also other metabolic disorders of MDS, promoting an up-to-date management philosophy. In this review, we aim to summarize the underlying mechanism, screening, diagnosis, prevention, and treatment of T2D, especially regarding the personalized selection of hypoglycemic agents and holistic management based on the concept of "MDS-related TOD".

Hypercoagulability is characterized by abnormal elevations of coagulation factor levels and increased thrombin generation potential. Prior studies demonstrated links between impaired glucose metabolism, endothelial dysfunction, and hypercoagulability. However, the associations between hypercoagulability and incident type 2 diabetes as well as its underlying mechanism remain unclear. We aimed to assess the associations between coagulation parameters including coagulation factor (F) VIII, FIX, FXI, fibrinogen, thrombin generation potential (lag time, endogenous thrombin potential [ETP], peak, time-to-peak, velocity) and incident type 2 diabetes, and to study the underlying mechanism by examining the mediating role of glycoprotein acetylation (GlycA). In the Netherlands Epidemiology of Obesity study, we applied a Cox Proportional-Hazards Model in 5718 participants after adjustment for confounders. We further conducted a mediation analysis investigating the mediation effect of GlycA on the observed associations. During a median follow-up of 6.7 years, 281 incident type 2 diabetes diagnoses were reported. Compared with the lowest quartile, hazard ratio (95% confidence interval) of the highest quartile was 2.47 (1.48-4.14) for FIX, 1.37 (0.85-2.20) for FVIII, 1.11 (0.76-1.63) for FXI, 0.98 (0.65-1.48) for fibrinogen, 1.56 (1.07-2.28) for ETP, 1.84 (1.23-2.74) for peak, 1.59 (1.08-2.33) for velocity, 0.92 (0.62-1.38) for lag time, and 1.21 (0.86-1.70) for time-to-peak. GlycA mediated only a small proportion of all observed associations. In conclusion, elevated levels of coagulation factor and thrombin generation potential are associated with incident type 2 diabetes, suggesting the involvement of hypercoagulability in the pathogenesis of type 2 diabetes.

Oxidative stress (OS) occurs from excessive reactive oxygen species or a deficiency of antioxidants-primarily endogenous glutathione (GSH). There are many illnesses, from acute and post-COVID-19, diabetes, myocardial infarction to Alzheimer's disease, that are associated with OS. These dissimilar illnesses are, in order, viral infections, metabolic disorders, ischemic events, and neurodegenerative disorders. Evidence is presented that in many illnesses, (1) OS is an early initiator and significant promotor of their progressive pathophysiologic processes, (2) early reduction of OS may prevent later serious and irreversible complications, (3) GSH deficiency is associated with OS, (4) GSH can likely reduce OS and restore adaptive physiology, (5) effective administration of GSH can be accomplished with a novel nano-product, the GSH/cyclodextrin (GC) complex. OS is an overlooked pathological process of many illnesses. Significantly, with the GSH/cyclodextrin (GC) complex, therapeutic administration of GSH is now available to reduce OS. Finally, rigorous prospective studies are needed to confirm the efficacy of this therapeutic approach.

Vascular organoids (VOs), derived from induced pluripotent stem cells (iPSCs), hold promise as in vitro disease models and drug screening platforms. However, their ability to faithfully recapitulate human vascular disease and cellular composition remains unclear. In this study, we demonstrate that VOs derived from iPSCs of donors with diabetes (DB-VOs) exhibit impaired vascular function compared to non-diabetic VOs (ND-VOs). DB-VOs display elevated levels of reactive oxygen species (ROS), heightened mitochondrial content and activity, increased proinflammatory cytokines, and reduced blood perfusion recovery in vivo. Through comprehensive single-cell RNA sequencing, we uncover molecular and functional differences, as well as signaling networks, between vascular cell types and clusters within DB-VOs. Our analysis identifies major vascular cell types (endothelial cells [ECs], pericytes, and vascular smooth muscle cells) within VOs, highlighting the dichotomy between ECs and mural cells. We also demonstrate the potential need for additional inductions using organ-specific differentiation factors to promote organ-specific identity in VOs. Furthermore, we observe basal heterogeneity within VOs and significant differences between DB-VOs and ND-VOs. Notably, we identify a subpopulation of ECs specific to DB-VOs, showing overrepresentation in the ROS pathway and underrepresentation in the angiogenesis hallmark, indicating signs of aberrant angiogenesis in diabetes. Our findings underscore the potential of VOs for modeling diabetic vasculopathy, emphasize the importance of investigating cellular heterogeneity within VOs for disease modeling and drug discovery, and provide evidence of GAP43 (neuromodulin) expression in ECs, particularly in DB-VOs, with implications for vascular development and disease.

Diabetic wounds are a severe complication of diabetes, characterized by persistent, non-healing ulcers due to disrupted wound-healing mechanisms in a hyperglycemic environment. Key factors in the pathogenesis of these chronic wounds include unresolved inflammation and antioxidant defense imbalances. The cystine/glutamate antiporter SLC7A11 (xCT) is crucial for cystine import, glutathione production, and antioxidant protection, positioning it as a vital regulator of diabetic wound healing. Recent studies underscore the role of SLC7A11 in modulating immune responses and oxidative stress in diabetic wounds. Moreover, SLC7A11 influences critical processes such as insulin secretion and the mTOR signaling pathway, both of which are implicated in delayed wound healing. This review explores the mechanisms regulating SLC7A11 and its impact on immune response, antioxidant defenses, insulin secretion, and mTOR pathways in diabetic wounds. Additionally, we highlight the current advancements in targeting SLC7A11 for treating related diseases and conceptualize its potential applications and value in diabetic wound treatment strategies, along with the challenges encountered in this context.

This commentary considers the similarities which exist between pressure ulcers (PUs) and diabetic foot ulcers (DFUs). It aims to describe what is known to be shared-both in theory and practice-by these wound types. It goes on to detail the literature surrounding the role of inflammation in both wound types. PUs occur following prolonged exposure to pressure or pressure in conjunction with shear, either due to impaired mobility or medical devices. As a result, inflammation occurs, causing cell damage. While DFUs are not associated with immobility, they are associated with altered mobility occurring as a result of complications of diabetes. The incidence and prevalence of both types of lesions are increased in the presence of multimorbidity. The prediction of either type of ulceration is challenging. Current risk assessment practices are reported to be ineffective at predicting when ulceration will occur. While systemic inflammation is easily measured, the presence of local or subclinical inflammation is harder to discern. In patients at risk of either DFUs or PUs, clinical signs and symptoms of inflammation may be masked, and systemic biomarkers of inflammation may not be elevated sufficiently to predict imminent damage until ulceration appears. The current literature suggests that the use of local biomarkers of inflammation at the skin's surface, namely oedema and temperature, may identify early tissue damage.

Nearly half of patients with diabetes experience diabetic peripheral neuropathy (DPN), resulting in a mere 53% survival rate within 3 years. Aberrations in coagulation function have been implicated in the pathogenesis of microvascular complications, prompting the need for a thorough investigation into its role as a contributing factor in the development and progression of DPN.

Data were gathered from 1211 type 2 diabetes patients admitted to five centers from September 2018 to October 2022 in China. DPN was evaluated by symptoms and electromyography. Motor and sensory nerve conduction velocity (NCV) was appraised and the NCV sum score was calculated for the median, ulnar, and peroneal motor or sensory nerves.

Patients with DPN exhibited alterations in coagulation function. (i) Specifically, they exhibited prolonged thrombin time (p = 0.012), elevated fibrinogen (p < 0.001), and shortened activated partial thromboplastin time (APTT; p = 0.026) when compared to the control group. (ii) After accounting for potential confounders in linear regression, fibrinogen, and D-dimer were negatively related to the motor NCV, motor amplitude values, and mean velocity and amplitude. Also, fibrinogen was associated with higher Michigan neuropathy screening instrument (MNSI) scores (β 0.140; p = 0.001). This result of fibrinogen can be validated in the validation cohort with 317 diabetic patients. (iii) Fibrinogen was independently associated with the risk of DPN (OR 1.172; p = 0.035). In the total age group, DPN occurred at a slower rate until the predicted fibrinogen level reached around 3.75 g/L, after which the risk sharply escalated.

Coagulation function is warranted to be concerned in patients with type 2 diabetes to predict and prevent the occurrence of DPN in clinical practice.

The poor nutritional characteristics and potentially harmful molecules in ultraprocessed foods (UPFs) are risk factors for diabetic microvascular complications. However, the evidence regarding UPFs and diabetic microvascular complications remains limited.

We aimed to evaluate the associations between UPF consumption and risk of diabetic microvascular complications, to examine the underlying biological pathways (e.g., inflammation and lipid profile), and to identify whether the associations differ by type of UPF dietary patterns.

We included a prospective cohort of UK Biobank participants with type 2 diabetes (T2D) having at least one 24-h dietary recall (N = 5685). UPFs were defined using the Nova classification. Principal component analysis was used to derive UPF consumption patterns. Associations of UPFs and their consumption patterns with microvascular complications were assessed using Cox proportional hazards regression models. Mediation analyses were used to estimate the mediating effects of 22 biomarkers.

During a median of 12.7 y of follow-up, 1243 composite microvascular complications events occurred (599 diabetic retinopathy, 237 diabetic neuropathy, and 662 diabetic kidney disease events). Five consumption patterns were identified (spread and bread, cereal prepared with liquids, dairy-based products, sugary beverage and snack, and mixed beverage and savory snack patterns). A 10% increment in the proportion of UPF was associated with higher hazards of the composite microvascular complications (hazard ratio [HR]: 1.08; 95% confidence interval [CI]: 1.03, 1.13) and diabetic kidney disease (HR: 1.13; 95% CI: 1.06, 1.20). Triglycerides, C-reactive protein, and body mass index collectively explained 22.0% (9.6%-43.0%) of the association between UPF intake and composite microvascular complications. Pattern high in mixed beverage and savory snack was associated with a higher risk of composite microvascular complications.

Higher UPF consumption was associated with higher risks of diabetic microvascular complications, and the association was partly mediated through multiple potential ways.

This study aims to investigate the pathogenesis of hyperglycemia and its associated vasculopathy using multiomics analyses in diabetes and impaired glucose tolerance, and validate the mechanism using the cell experiments.

In this study, we conducted a comprehensive analysis of the metagenomic sequencing data of diabetes to explore the key genera related to its occurrence. Subsequently, participants diagnosed with impaired glucose tolerance (IGT), and healthy subjects, were recruited for fecal and blood sample collection. The dysbiosis of the gut microbiota (GM) and its associated metabolites were analyzed using 16S rDNA sequencing and liquid chromatograph mass spectrometry, respectively. The regulation of gene and protein expression was evaluated through mRNA sequencing and data-independent acquisition technology, respectively. The specific mechanism by which GM dysbiosis affects hyperglycemia and its related vasculopathy was investigated using real-time qPCR, Western blotting, and enzyme-linked immunosorbent assay techniques in HepG2 cells and neutrophils.

Based on the published data, the key alterable genera in the GM associated with diabetes were identified as Blautia, Lactobacillus, Bacteroides, Prevotella, Faecalibacterium, Bifidobacterium, Ruminococcus, Clostridium, and Lachnoclostridium. The related metabolic pathways were identified as cholate degradation and L-histidine biosynthesis. Noteworthy, Blautia and Faecalibacterium displayed similar alterations in patients with IGT compared to those observed in patients with diabetes, and the GM metabolites, tauroursodeoxycholic acid (TUDCA) and carnosine (CARN, a downstream metabolite of histidine and alanine) were both found to be decreased, which in turn regulated the expression of proteins in plasma and mRNAs in neutrophils. Subsequent experiments focused on insulin-like growth factor-binding protein 3 and interleukin-6 due to their impact on blood glucose regulation and associated vascular inflammation. Both proteins were found to be suppressed by TUDCA and CARN in HepG2 cells and neutrophils.

Dysbiosis of the GM occurred throughout the entire progression from IGT to diabetes, characterized by an increase in Blautia and a decrease in Faecalibacterium, leading to reduced levels of TUDCA and CARN, which alleviated their inhibition on the expression of insulin-like growth factor-binding protein 3 and interleukin-6, contributing to the development of hyperglycemia and associated vasculopathy.

Both chronic hepatitis B (CHB) and stroke contribute to a high burden of disease in the majority of low- and middle-income countries. Epidemiological studies yield conflicting results on the association between CHB and stroke, and the causal relationship remains inconclusive. This study aimed to assess the causal effects of CHB on stroke and its subtypes in East Asians by Mendelian randomization (MR) analysis. Variants associated with CHB were obtained from a genome-wide association study (GWAS) of Chinese samples as instrumental variables. The summary statistics for stroke in East Asians were derived from the largest published GWAS to date. Two-sample MR analyses were implemented to evaluate the causal effects of CHB on stroke and its subtypes by using the canonical inverse variance weighting method and other supplementary approaches. We observed an association between genetic predisposition to CHB and a decreased risk of large-artery atherosclerotic stroke (odds ratio = 0.872, 95% confidence interval = 0.786-0.967, p = 0.010). The causal effects of CHB on other stroke outcomes were not statistically significant. Evidence for heterogeneity and horizontal pleiotropy were not found in our analyses. This study provides genetic evidence for a negative association between CHB and stroke in East Asians, which helps improve our understanding of the etiology of stroke.

Neuropathy is the most common disorder comprising peripheral nerve damage in diabetic patients. Prolonged hyperglycaemia and oxidative stress cause metabolic imbalance and are the key reasons for the development of diabetic neuropathy. Daidzein, a soy isoflavone possesses potent anti-hyperglycaemic and antioxidant activity. The present study aims to check the protective effect of Daidzein in diabetic neuropathy in rats. The experimental animal model involved induction of diabetes in rats by intraperitoneal injection of streptozotocin (55 mg/kg). Following confirmation of diabetes, the diabetic rats were subjected to oral treatment with varying doses of Daidzein (25, 50, and 100 mg/kg) and pregabalin (30 mg/kg) for a duration of 4 weeks, initiated 6 weeks after diabetes induction. Results indicated that Daidzein treatment led to a significant reduction in plasma glucose levels and an improvement in body weight among diabetic animals. Moreover, Daidzein demonstrated a positive impact on sensory functions, as evidenced by the effect on tail withdrawal and response latency. Mechanical hyperalgesia and allodynia, common symptoms of diabetic neuropathy, were also significantly reduced with both Daidzein and pregabalin treatment. Notably, nerve conduction velocities exhibited improvement following the administration of Daidzein and pregabalin. Further investigation into the molecular mechanisms revealed that Daidzein treatment resulted in a notable enhancement of antioxidant enzyme levels and a reduction in the overexpression of NOX-4 in the sciatic nerve. This suggests that Daidzein's therapeutic effect is associated with the inhibition of oxidative stress via NOX-4. In summary, the findings of study suggests that, Daidzein treatment significantly attenuated diabetic neuropathy by inhibiting oxidative stress via NOX-4 inhibition.