Background Type 2 diabetes mellitus is a common metabolic disorder associated with progressive vascular complications. Microvascular dysfunction is an important cause of diabetic nephropathy, retinopathy, and neuropathy. Oxidative stress and prothrombotic activity are considered major contributors to vascular injury among diabetic patients. This study aimed to evaluate the association of prothrombotic and oxidative stress biomarkers with microvascular dysfunction risk in patients with type 2 diabetes mellitus. Methods This hospital-based observational cross-sectional study was conducted at Maryam Medicare Hospital, Vehari, Pakistan, from February 2025 to January 2026. A total of 200 patients with type 2 diabetes mellitus were included using consecutive sampling. Patients were divided into low-risk and high-risk microvascular dysfunction groups based on clinical and biochemical assessment. Prothrombotic biomarkers including fibrinogen, D-dimer, and plasminogen activator inhibitor-1 (PAI-1) were measured along with oxidative stress biomarkers including malondialdehyde (MDA), total antioxidant capacity (TAC), superoxide dismutase (SOD), glutathione (GSH), and catalase activity. Statistical analysis was performed using IBM SPSS Statistics for Windows, Version 26 (Released 2018; IBM Corp., Armonk, New York, United States). Results Patients with high microvascular dysfunction risk showed significantly increased fibrinogen (421.5 ± 72.4 vs 312.8 ± 48.6 mg/dL), D-dimer (458.7 ± 101.5 vs 228.4 ± 62.1 ng/mL), PAI-1 (34.2 ± 8.7 vs 18.7 ± 5.4 ng/mL), and MDA levels (4.86 ± 0.92 vs 2.41 ± 0.58 nmol/mL) compared with the low-risk group (p < 0.001). Antioxidant biomarkers including TAC, SOD, GSH, and catalase were significantly reduced in high-risk patients (p < 0.001). MDA showed the highest predictive value for microvascular dysfunction risk with an area under the curve (AUC) of 0.871. Conclusion Elevated thrombotic and oxidative stress biomarkers were significantly associated with the presence of microvascular complications in patients with type 2 diabetes mellitus. These findings suggest that these biomarkers may reflect the burden of vascular injury and oxidative stress in patients with established diabetic microvascular complications.

Resveratrol appears to offer greater cognitive benefit to compromised models, such as in type II diabetes mellitus, menopause, and high body mass index (BMI), relative to healthy cohorts. With regards high BMI, hypertension, insulin resistance, oxidative stress, and inflammation have been posited as mechanisms underpinning cognitive decrements, and recent advancements in gut-brain-axis research have linked high BMI with inflammation via gut dysbiosis. Polyphenols have been evidenced to act prebiotically in the gut, to mediate anti-inflammatory effects in animal models, and this presents a mechanism by which resveratrol could bolster cognition in high BMI individuals.

The current study investigates whether resveratrol can confer cognitive benefit to individuals with a high BMI, and whether these effects coincide with changes in the gut microbiome, urinary metabolome and biological markers of adiposity (anthropomorphic and blood biomarkers) and inflammation/oxidation.

N = 99 male and females (35-60 years, mean age 47.51 years), with a BMI between 25 and 42 kg/m², received either 500 mg Veri-te™ resveratrol, or placebo, daily for 12 weeks. This supplementation period was bookended by visits to the laboratory for urine, blood, and stool sampling, and cognitive testing, which was assessed pre-and post-dose during both the acute and chronic testing visit.

Participants in the placebo control group presented with existing differences on cognitive outcomes at baseline, which makes interpretation of apparent improvements in this group relative to resveratrol, problematic. No significant differences were observed within or between groups on any microbiome, urinary metabolome, biological markers of adiposity or inflammation/oxidation markers.

The absence of effects on the underlying biological mechanisms rationalized to underpin cognitive improvements in high BMI individuals likely explains the null results in the resveratrol intervention group. Effects attributed to the placebo control condition are explained as the persistence of pre-existing effects in this group of participants, and this may underlie the need to factor pre-enrolment aptitude into randomization in nutritional intervention trials. The lack of change in the gut microbiome of a healthy human cohort, following 12 weeks of resveratrol supplementation, is a positive indication, showing no deleterious disruption within this environment. Future studies may wish to investigate these effects in those with a disrupted gut microbiome.

The study was pre-registered on clinicaltrials.gov (identifier: NCT03448094).

Routine primary-care health examinations can identify clustered metabolic, renal-urinary, medication-related, and functional screening abnormalities in older adults, but their value for screening-derived abnormality-burden assessment in rural ageing populations remains underexplored.

This community-based cross-sectional secondary analysis used 2025 annual health-examination data from Wangkui County, Heilongjiang Province, Northeast China. The analytic sample included 1,163 women aged ≥65 years. High screening-derived abnormality burden was constructed from routinely available screening indicators and was not intended to diagnose constipation, bowel dysfunction, frailty, or any clinical disease endpoint. Diabetes-related exposure was defined as self-reported diabetes, fasting plasma glucose ≥7.0 mmol/L, or glucose-lowering medication use. Labour-type physical activity was assessed as a secondary contextual routine-record variable using a cohort-specific index derived from weekly frequency and duration. Associations were estimated using modified Poisson regression with robust HC3 standard errors.

High screening-derived abnormality burden was present in 27.52% of participants, and diabetes-related exposure was present in 22.53%. Diabetes-related exposure was associated with higher abnormality burden in the primary adjusted model and remained similar after BMI adjustment (PR 1.614, 95% CI 1.329-1.961). In the key non-metabolic sensitivity analysis excluding triglycerides, HDL-C, and BMI abnormality, diabetes-related exposure remained positively associated with high non-metabolic abnormality burden (PR 1.463, 95% CI 1.077-1.988). LowActive and HighActive were not independently associated with high abnormality burden and were interpreted as contextual findings rather than as primary physical-activity evidence.

Among older rural women, diabetes-related exposure was associated with higher screening-derived abnormality burden. Labour-type physical activity did not independently distinguish abnormality-burden status under the available crude routine-record measurement framework. This internally derived outcome should be interpreted as exploratory clustering of routine screening abnormalities for primary-care triage, not as a validated geriatric phenotype or clinical diagnostic endpoint. From an aging-and-public-health perspective, these findings suggest that routine older-adult health examinations in underserved rural communities may provide a scalable opportunity for population-level risk recognition, follow-up prioritisation, health guidance, and referral review among older women living with diabetes-related screening burden, while avoiding diagnostic over interpretation.

Diabetic foot ulcers (DFUs) are the leading cause of amputations in people with diabetes, mainly due to poor wound healing. This study evaluated DFU trial designs and analysed observational data from the two prospective Diabetic Foot Consortium (DFC) studies to estimate longitudinal healing and amputation rates, assess the effects of wound surface area and duration on healing, and inform sample size considerations for future trials. We analysed data from Open Wound Master Protocol (MP, n = 419) and c-Myc Biomarker (n = 140). The primary outcome was complete wound healing. Time-to-event analysis estimated healing and amputation rates, with amputations classified as non-healed. Logistic regression assessed the prediction of healing based on baseline wound characteristics, with model performance evaluated using AUC (area under the curve). Sample size calculations were performed to achieve 80% power. In the MP study, healing rates were 26% by week 12% and 49% by week 32; amputation rates were 4% and 10%, respectively. The c-Myc study showed 38% healing and 2.5% amputation by week 12. Wound area and duration significantly predicted healing (AUC ≥ 0.70 by 24 weeks). For smaller treatment effects, predicted healing rates varied by up to 40% between small and large wounds, impacting sample size. Contemporary DFU trial designs and healing times remained largely unchanged over two decades. While shorter trials (e.g., 12 weeks) theoretically require smaller sample sizes due to reduced outcome variance, they risk failing to capture the full treatment effect. Trial design must account for baseline wound characteristics, which should inform eligibility criteria and follow-up.

To investigate the barriers and facilitators to adopting healthy lifestyle habits among patients with type 2 diabetes mellitus (T2DM) in the Brazilian Amazon, using the Environmental Factors domain of the International Classification of Functioning, Disability and Health (ICF) as a conceptual framework.

A qualitative study was conducted with 47 patients with T2DM and 17 community health workers (CHWs) from primary health care services in the Brazilian Amazon. Data were collected through two World Café group discussion sessions (one involving patients and one involving CHWs) and 15 semi-structured interviews conducted in patients' homes. Data were analysed using thematic analysis supported by Atlas.ti 24 software.

Three major categories emerged: attitudinal, social and physical factors. Attitudinal barriers included resistance to behaviour change, denial of disease severity and physical limitations, whereas fear of complications and valuing life motivated healthier behaviours. Social barriers comprised lack of family support, insecurity and transportation difficulties, while family involvement, professional guidance and trust in CHWs facilitated treatment adherence and lifestyle modification. Physical barriers included inadequate infrastructure, adverse weather conditions and the absence of safe public spaces for physical activity. Conversely, proximity to local markets and fairs facilitated access to healthy foods and supported dietary improvements.

Barriers and facilitators to healthy lifestyle adoption among people with T2DM in the Brazilian Amazon are strongly influenced by attitudinal, social and environmental factors. Effective diabetes management in this context requires culturally sensitive interventions, improved urban infrastructure, strengthened community support networks and continued engagement of multidisciplinary healthcare teams, particularly CHWs. These findings provide important insights for developing context-specific strategies to promote sustainable lifestyle changes, enhance patient autonomy and improve quality of life in remote Amazonian communities.

Therapeutic inertia is a major barrier to optimal glycemic control in type 2 diabetes (T2DM), yet its impact in low-resource settings is not well-documented. This retrospective cohort study investigated the effect of therapeutic inertia on treatment outcomes in patients with T2DM receiving care at a tertiary hospital in southern Ethiopia.

A retrospective cohort study was conducted among 159 adult ambulatory T2DM patients between June 2020 and 2023. Data were collected from medical records. The primary outcome was poor treatment outcome, defined as fasting blood glucose > 130 mg/dL or development of a new diabetes-related complication. Exposure was defined as failure to intensify treatment within three months of uncontrolled glycemia. Cox proportional hazard models were used to assess the association between therapeutic inertia and poor treatment outcomes.

The medical records of 159 T2DM patients were reviewed. Poor treatment outcomes were common in the therapeutic inertia group (68.6%). The therapeutic inertia exposure group was significantly associated with an increased risk of poor treatment outcomes, with an adjusted HR of 1.927 (95% CI: 1.201-3.092, p = 0.007). As a secondary analysis, factors such as physician qualification (p = 0.001), presence of comorbidities (p = 0.024), and the presence of neuropathy (p = 0.02) and nephropathy (p = 0.011) were significantly associated with therapeutic inertia.

Therapeutic inertia was significantly associated with worse treatment outcomes in this cohort. Healthcare systems should implement strategies to promote proactive diabetes management, while recognizing that therapeutic inertia is a complex issue influenced by patient, provider, and system factors. Future research should focus on identifying and overcoming the contextual barriers to timely treatment intensification.

Cabotegravir (CAB) is an integrase strand transfer inhibitor and the first long-acting injectable antiretroviral agent for human immunodeficiency virus (HIV), administered with rilpivirine. Because approval in Japan relied largely on overseas and international collaborative trials, domestic real-world evidence remains limited. This study evaluated the real-world safety and effectiveness of CAB in people living with HIV (PLHIV) in Japan.

This interim analysis (June 27, 2022 and June 17, 2025) was part of an ongoing post-marketing surveillance of Japanese PLHIV treated with CAB at institutions participating in the HIV-related Drugs Cooperative Survey. Safety was assessed by the incidence of adverse drug reactions (ADRs). Associations between ADR incidence and background characteristics were examined using Fisher's exact and χ² tests without multiplicity adjustment. Effectiveness was evaluated using virologic suppression assessed by log-transformed HIV RNA copies/mL and peripheral CD4⁺ cell counts.

A total of 121 and 117 participants were included in the safety and efficacy analysis sets, respectively; most were aged over 20 years, and over 96% were male participants. Overall, 76 ADRs were reported in 45 participants (37.19%). The most frequent ADRs were injection site pain and musculoskeletal pain (12.40% each). Four serious ADRs that were not explicitly deemed unrelated to CAB by the reporting physicians occurred in 4 participants: hepatitis B reactivation, monkeypox, syphilis, and type 2 diabetes mellitus. Stratification analyses by participant characteristics revealed high ADR incidences among participants aged ≥ 30 to < 40 years (p = 0.038), without allergy (p = 0.016), and with comorbidities (p = 0.045). HIV RNA copies remained suppressed and CD4⁺ cell counts were maintained at levels comparable to treatment initiation throughout follow-up.

This interim analysis indicates that CAB therapy is safe, with no new safety signals, and effective, as demonstrated by sustained virological suppression and stable CD4⁺ cell counts. These findings are consistent with outcomes reported in overseas and international collaborative clinical studies.

Combining immunotherapy with targeted therapy represents a promising trajectory for cancer treatment; however, safety profiles remain insufficient. This study aimed to characterize adverse events associated with immune-targeted regimens in hepatocellular carcinoma (HCC).

This study used Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), and Bayesian Confidence Propagation Neural Network (BCPNN) to detect signals of adverse events based on data from FDA Adverse Event Reporting System.

Signals of fulminant type-1 diabetes mellitus (ROR = 13.3, PRR = 13.2, IC = 3.7), myositis (8.5, 8.3, 3.1), encephalitis (8.4, 8.3, 3.0), and myocarditis (7.3, 7.2, 2.8) were identified in atezolizumab+bevacizumab. Immune-mediated hepatitis (5.6, 5.1, 2.4), hepatic encephalopathy (3.3, 3.0, 1.6), and uppergastrointestinal haemorrhage (4.3, 4.2, 2.1) were associated with pembrolizumab+lenvatinib. Signals of gastrointestinal haemorrhage (5.1, 4.8, 2.3) and malignant neoplasm progression (2.9, 2.7, 1.4) were in patients using atezolizumab+cabozantinib.

This study delineated distinct profiles of adverse events associated with immunotargeted therapies, which serves as a critical reference for risk assessment and therapeutic selection. Though atezolizumab plus bevacizumab is recommended as first-line treatment for advanced HCC, potential severe immune-mediated adverse events affecting multiple organs suggested the importance of clinical vigilance. Extrapolation of pembrolizumab+lenvatinib and atezolizumab+cabozantinib from other cancers to HCC warrants caution in consideration of the associated bleeding risks and hepatic complications.

Diabetes mellitus is a complex, multifactorial metabolic disorder characterized by chronic hyperglycemia and progressive organ dysfunction. Conventional diagnostic and prognostic markers such as fasting glucose and glycated hemoglobin provide limited insight into disease heterogeneity, early molecular changes, and individualized risk of complications. In recent years, RNA-based biomarkers have emerged as powerful tools for capturing dynamic regulatory processes underlying diabetes onset, progression, and therapeutic response. These biomarkers include messenger RNAs (mRNAs), microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and transfer RNA-derived fragments (tRFs), which collectively orchestrate gene expression, metabolic signaling, immune modulation, and cellular stress responses. This review comprehensively examines the landscape of RNA-based biomarkers in diabetes, highlighting their mechanistic relevance, detection platforms, clinical utility, and translational challenges. We discuss how regulatory RNA networks reflect beta-cell dysfunction, insulin resistance, inflammation, and tissue-specific pathology, and how their integration into liquid biopsy approaches and computational frameworks may redefine precision diagnostics and personalized diabetes care.

Recent trials support the superior efficacy of clopidogrel compared to aspirin monotherapy after completion of dual antiplatelet therapy (DAPT) in patients who have undergone percutaneous coronary intervention (PCI). However, limited evidence is available in patients with diabetes mellitus (DM).

The current study sought to evaluate the comparative efficacy and safety of clopidogrel vs aspirin monotherapy according to the presence of DM.

This was a prespecified analysis of the SMART-CHOICE 3 trial, which was a multicenter, open-label, randomized controlled trial comparing clopidogrel vs aspirin monotherapy in patients with complex coronary lesions or high-risk clinical characteristics. From August 2020 to July 2023, a total of 5,506 patients who underwent PCI and standard DAPT duration and had complex coronary lesions, DM, or previous myocardial infarction, were randomized to clopidogrel or aspirin monotherapy groups. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), which was defined as a composite of death from any cause, myocardial infarction, or stroke.

Of 5,506 patients, 2,089 had DM (1,039 in the clopidogrel group and 1,050 in the aspirin group). At a median follow-up of 2.3 years (IQR: 1.6-3.0 years), DM patients had a higher risk of MACCE compared to non-DM patients (6.8% vs 4.7%; HR: 1.44, 95% CI: 1.10-1.87, P = 0.008). Clopidogrel showed a significantly lower risk of MACCE than aspirin in DM patients (4.5% vs 9.1%; HR: 0.57, 95% CI: 0.38-0.86, P = 0.008). There was no significant interaction between DM and antiplatelet monotherapy regarding MACCE (P for interaction = 0.124). The risk of bleeding was comparable between the 2 groups in DM patients (2.9% vs 2.9%; HR: 1.06, 95% CI: 0.57-1.95, P = 0.855).

Among DM patients who completed the standard duration of DAPT after PCI, clopidogrel monotherapy was associated with a lower risk of a composite of death from any cause, myocardial infarction, and stroke compared with aspirin monotherapy, without increased rates of bleeding. There was no significant interaction between DM and antiplatelet monotherapy with respect to MACCE. (SMART-CHOICE 3 [SMart Angioplasty Research Team: CHoice of Optimal Anti-Thrombotic Strategy in Patients Undergoing Implantation of Coronary Drug-Eluting Stents 3]; NCT04418479).