Patients with end-stage kidney disease (ESKD) have been largely excluded from randomized trials of sodium-glucose cotransporter-2 inhibitors (SGLT2is). Despite the lack of guideline recommendations, SGLT2i prescriptions occur in real-world clinical practice. We aimed to describe real-world associations between SGLT2i exposure and clinical outcomes among patients with type 2 diabetes mellitus (T2DM) coded with ESKD. We conducted a target trail emulation with retrospective, new-user, active-comparator cohort study using the TriNetX US Collaborative Network (2016-2023). Adults with T2DM and ESKD who initiated an SGLT2i or a dipeptidyl peptidase-4 inhibitor (DPP4i) were included. Propensity score matching (1:1) was used to balance baseline characteristics. The primary outcome was all-cause mortality; secondary outcomes included sepsis, pneumonia, major adverse cardiovascular events (MACE), all-cause hospitalization, and emergency department visits. Subgroup analyses were exploratory, and heterogeneity was assessed using Cochran's statistics. After matching, 5295 SGLT2i users were compared with 5295 DPP4i users. Over a follow-up of up to 4 years, SGLT2i exposure was associated with lower all-cause mortality (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.84-0.97), sepsis (HR 0.87, 95% CI 0.79-0.95), and all-cause hospitalization (HR 0.93, 95% CI 0.89-0.97). No significant associations were observed for MACE, pneumonia, or emergency department visits. Subgroup-specific estimates varied in magnitude, with no consistent evidence of heterogeneity. In this large real-world cohort of patients coded with ESKD, SGLT2i exposure was associated with favorable outcome patterns compared with DPP4i. Given the observational design, potential misclassification of kidney disease status, and off-label drug use, these findings should be interpreted as hypothesis-generating and do not establish causality.

Endoplasmic reticulum stress (ERS), caused by excessive buildup of misfolded proteins in the ER lumen, has emerged as a major contributor to diabetes mellitus (type-1 and type-2; T1DM and T2DM), leading to β-cell dysfunction, insulin resistance, and related comorbidities. In this review, we aim to characterize the signal transduction pathways in normal versus diseased conditions and their impact on the development of insulin-dependent and insulin-independent diabetes.

Evidence on ERS and diabetes were searched in MEDLINE and Google scholar databases using search strings that incorporated synonyms of ERS, diabetes, β-cell dysfunction and insulin resistance and their impact in disease progression. Our search was guided by the pertinent keywords as mentioned in the "keywords" section, that encompassed past twenty-five years of body of literature in this field as evident from Urano et al. 2000 till Sue et al. 2025.

Our results and conclusion are the distillation of past two and half decades of scientific research dedicated towards understanding the biology of ERS dependent diabetes. The ERS-induced Unfolded Protein Response (UPR), comprising of three signaling cascades, is pivotal in either protecting against or contributing to the pathophysiology of T1DM and T2DM. Clinically, ERS manifests as insulin resistance, heightened inflammation, and β-cell destruction. Consequently, ERS effectors and proteins involved in the UPR pathways have become attractive targets for pharmacological investigation. We also review some of the protein biomarkers of ERS dependent diabetes and relevant in vivo/ex vivo models used in clinical versus preclinical settings, as well as the latest state-of-the-art targeted molecular and cellular therapies that are currently being tried for the diabetic patients.

Diabetes mellitus-induced erectile dysfunction (DMED) is a highly prevalent complication among diabetic patients; however, its underlying pathogenic mechanisms remain incompletely understood. Metabolic disorder is a hallmark of diabetes, yet its precise contribution to DMED progression is not well defined. In this study, we demonstrate that metabolic disturbances, particularly elevated levels of palmitic acid (PA), induce ferroptosis in corpus cavernosum fibroblasts, thereby contributing to the development of erectile dysfunction. Mechanistically, we identified ZDHHC9, a palmitoyltransferase, to be aberrantly upregulated in DMED, where it catalyzes the S-palmitoylation of ACSL4 at cysteine 595. This post-translational modification enhances ACSL4 enzymatic activity, promotes lipid peroxidation, and drives ferroptosis in fibroblasts. Furthermore, we found that hyperactivation of the PI3K/AKT signaling pathway serves as a key upstream regulator of ZDHHC9 expression in this context. To explore the therapeutic potential of targeting this pathway, we developed siRNA against Zdhhc9 encapsulated in lipid nanoparticles (siZdhhc9-LNPs), which effectively suppressed Zdhhc9 expression in the corpus cavernosum and ameliorated erectile dysfunction in DMED mice. Collectively, our findings reveal a pathological cascade linking metabolic dysregulation to fibroblast ferroptosis via ZDHHC9-mediated ACSL4 palmitoylation, and establish ZDHHC9 as a promising therapeutic target for the treatment of DMED.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is more severe in people with diabetes mellitus due to immune dysfunction, exacerbated inflammation and increased risk of co-morbidities and mortality. In this context, this study aims to analyse the epidemiological profile of hospitalized people with diabetes mellitus and COVID-19 in Brazil over 4 years of the pandemic.

The epidemiological analysis was conducted using data from the Open-Data-SUS (Sistema Único de Saúde, Brazilian Unified Health System) platform (Brazilian Ministry of Health) covering the period from March 2020 to March 2024. Data were processed in Statistical Package for the Social Sciences software, with missing values imputed using XLSTAT. Variables included demographic profile, viral infection, co-morbidities, clinical signs and symptoms, intensive care unit (ICU) admission and mechanical ventilation, and outcomes. Statistical analyses comprised bivariate and multivariable logistic regression with a 5% significance level, focusing on two primary comparisons: the risk of death and the likelihood of classification as diabetes mellitus. The study protocol was approved by the institutional ethics committee.

Among 2,078,062 people hospitalized with SARS-CoV-2 in Brazil, 22.2% (N = 461,647) had diabetes mellitus, with marked regional heterogeneity in both prevalence and mortality. Overall mortality was 32.9% (N = 683,088). Diabetes mellitus was not only highly prevalent but also emerged as an independent risk factor for in-hospital death, significantly increasing mortality odds (OR = 1.178; 95% confidence interval [95% CI] = 1.168-1.188), as well as higher likelihood of ICU admission (OR = 1.102; 95% CI = 1.093-1.112) and invasive mechanical ventilation (OR = 1.102; 95% CI = 1.087-1.118). Older age, female sex and self-identification as Black, mixed-race or Asian were also strongly associated with diabetes mellitus. The presence of co-morbidities, such as cardiopathy (heart disease), kidney disease, obesity, liver disease, and neurological disorders further amplified the risk of poor outcomes. Regarding vaccination, most people were unvaccinated, and while COVID-19 vaccination showed a modest association with DM diagnosis, it consistently reduced the risk of death (OR = 0.588; 95% CI = 0.583-0.594). Conversely, nosocomial infection substantially increased mortality risk, despite presenting a divergent pattern in relation to diabetes mellitus in adjusted models. Clinical symptoms most strongly associated with death included dyspnoea, respiratory discomfort and peripheral oxygen saturation below 95%. Hospital management variables were decisive: ICU admission and ventilatory support, especially invasive mechanical ventilation (OR = 12.933; 95% CI = 12.752-13.115), markedly increased mortality. Overall, advanced age remained the strongest predictor, with individuals older than 85 years experiencing more than a 30-fold increased risk of death compared with younger groups (OR = 32.840; 95% CI = 30.840-34.969).

Diabetes mellitus is an independent predictor of worse outcomes in hospitalized people with COVID-19 in Brazil. Mortality is strongly influenced by age, co-morbidities and severity markers, while vaccination provides substantial protection.

Type 2 diabetes mellitus (T2DM) is a chronic condition with significant psychological and physiological challenges. Clinical hypnosis has emerged as a complementary intervention to support emotional regulation and self-management in T2DM care. This critical narrative review evaluates empirical studies on the use of clinical hypnosis for managing psychological and physiological outcomes in individuals with T2DM. Systematic search procedures were applied in Scopus, PubMed, and Google Scholar, yielding six eligible studies published between 2011 and 2025 for inclusion in this critical narrative review. The findings suggest potential benefits in reducing stress and anxiety, enhancing self-care, and improving glycemic control. However, methodological limitations - such as non-randomized designs, small samples, and heterogeneous protocols - limit causal conclusions and replicability. Clinical hypnosis shows promise as an adjunctive approach in T2DM management, but further research using rigorous designs and objective measures is needed to establish its effectiveness and mechanisms.

The precise diagnosis and scientific management of diabetes are highly important for improving patients' quality of life and reducing the risk of complications. However, in actual clinical settings, diagnostic processes often face challenges, including significant individual differences among patients, complex and diverse parameters, and heterogeneity in disease progression. These challenges not only impose greater requirements on the adaptability and precision of diagnostic and therapeutic models but also highlight the need for explainable disease mechanisms and rational treatment strategies. To address these issues, this study proposes an Extended Belief Rule Base (EBRB) model based on neighborhood covering reduction, abbreviated as NCR-EBRB, for diabetes prediction and diagnosis. During the model construction phase, the Extreme Gradient Boosting (XGBoost) method is first employed for feature importance evaluation to reasonably screen key features and effectively reduce model dimensionality. In the model inference phase, the Neighborhood Covering Reduction (NCR) method is adopted to implement rule reduction in the rule base, combined with a threshold-based rule activation strategy to filter out inefficient rules, ensuring efficient reasoning processes and effective result output. During the model optimization phase, the Projection Covariance Matrix Adaptive Evolution Strategy (P-CMA-ES) is applied to optimize the parameters of the streamlined rule base, aiming to identify optimal parameter configurations for further improving model performance. Through this meticulous parameter tuning, the diagnostic accuracy is enhanced, and the robustness of the model is improved.

Monoclonal gammopathy of renal significance (MGRS) refers to a spectrum of kidney disorders caused by monoclonal immunoglobulins produced by small, often clinically silent clones of B-cells or plasma cells that do not meet the diagnostic criteria for overt haematological malignancy. These entities are frequently overlooked, as their clinical presentation often mimics more common renal diseases and typical markers of monoclonal protein may be absent. We describe the case of a 49-year-old woman with type 2 diabetes and hypertension who presented with nephrotic-range proteinuria. Despite unremarkable findings on serum and urine protein electrophoresis and a normal bone marrow biopsy, serum free light chain analysis revealed significantly elevated kappa chains. Renal biopsy demonstrated classic features of both kappa light chain cast nephropathy and light chain deposition disease. This case highlights the role of renal biopsy and serum free light chain assays in the diagnosis of MGRS, especially when traditional paraprotein studies are inconclusive.

To assess long-term trends, regional disparities, determinants, and quality of care for type 2 diabetes mellitus (T2DM) among women aged 55 years or above worldwide.

Using Global Burden of Disease 2023 data, we quantified incidence, mortality, and disability-adjusted life years (DALYs) attributable to T2DM among women aged 55 years or above from 1990 to 2023. Temporal trends were evaluated using joinpoint regression. Regional determinants were identified through explainable machine learning models (XGBoost with Shapley Additive Explanations). A Quality-of-Care Index, derived from mortality, disability, and prevalence indicators, was constructed to evaluate health care performance.

In 2023, South Asia recorded the largest absolute burden of T2DM among women aged 55 years or above, with 749,064 cases (95% uncertainty intervals [UI] 592,209-892,315), 274,542 deaths (171,620-381,640), and 8.11 million DALYs (5.82-10.43 million), followed by East Asia and high-income North America. From 1990 to 2023, Eastern Europe exhibited the steepest long-term increases in age-standardized incidence, mortality, and DALYs rates, with an average annual percent change of 2.49% for incidence and 3.97% for mortality. Mortality and DALYs burdens peaked among women aged 65-69 years. Across regions, high fasting plasma glucose, high body mass index, and low physical activity were the leading contributors to disease burden. Distinct regional risk patterns were observed, including air pollution in Asia, unhealthy dietary patterns in high-income North America, sedentary behavior in Oceania, and alcohol use in South Asia. Lower Quality-of-Care Index scores were strongly associated with higher mortality and DALYs rates, highlighting substantial inequities in diabetes care.

The escalating burden of T2DM among women aged 55 years or older reflects interactions between biological aging and metabolic, behavioral, and environmental risks. Age-targeted prevention, improved care quality, and mitigation of modifiable exposures are critical to reduce diabetes-related disability globally.

The optimal timing of radiotherapy (RT) in patients with WHO grade 2 meningiomas remains controversial, particularly following gross total resection (GTR). This multicenter study compared long-term outcomes of early RT versus late RT, focusing on progression-free survival (PFS), overall survival (OS), and tumor-related mortality.

This retrospective multicenter cohort study included 263 adult patients with histopathologically confirmed WHO grade 2 meningiomas treated between 2005 and 2023. Patients were stratified by RT timing: early adjuvant RT after initial surgery versus late RT administered after radiologic or clinical progression. Outcomes were analyzed in the overall cohort and in a prespecified GTR subgroup. PFS and OS were estimated using the Kaplan-Meier method. Tumor-related mortality was assessed using cause-specific Cox and Fine-Gray competing-risk models.

With a median follow-up exceeding 7 years, early RT was associated with a significant improvement in PFS compared with late RT. In the overall cohort, 10-year PFS was 84.8% with early RT versus 18.6% with late RT (p < 0.001). Among patients undergoing GTR, 10-year PFS remained high with early RT (89.3%) but declined markedly after late RT (18.8%; p < 0.001). RT timing was the strongest independent predictor of PFS in multivariable models, although its effect attenuated over time. Tumor-related mortality was approximately sixfold higher in the late RT group (16.7% vs 2.7%; p = 0.011), whereas all-cause mortality did not differ significantly (24.2% vs 14.7%; p = 0.198). Mitotic count and Ki-67 index were independently associated with early and long-term PFS, whereas male sex, older age, and subtotal resection predicted tumor-related mortality.

Early RT provides a durable and clinically meaningful PFS benefit over late RT in WHO grade 2 meningiomas, including after GTR, without conferring an OS advantage. These findings emphasize the importance of RT timing and tumor biology in postoperative risk stratification and support consideration of early RT in selected patients, pending results from randomized trials.

Paclitaxel-induced peripheral neuropathy (CIPN) is a debilitating side effect affecting up to 70% of patients receiving paclitaxel chemotherapy, with severe symptoms occurring in approximately 30%. While non-modifiable risk factors such as age and genetics have been established, the role of modifiable factors, including vitamin D insufficiency, remains poorly characterized. This study aimed to evaluate the association between pre-treatment vitamin D levels and the incidence of severe CIPN in breast cancer patients receiving paclitaxel-based chemotherapy. A prospective cohort study was conducted on 300 breast cancer patients (stage I-III) receiving paclitaxel-based chemotherapy (80 mg/m²) for 12 weeks at Kafrelsheikh University Hospitals. Baseline serum 25(OH)D was quantified using the Elecsys Vitamin D Total II assay on the Cobas e411 platform, standardized to the VDSP reference method. Pre-treatment vitamin D levels were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS), with insufficiency defined as ≤ 20 ng/mL. CIPN was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20-item scale (EORTC QLQ-CIPN20), with particular focus on grade 3-4 sensory neuropathy. Statistical analyses included receiver operating characteristic (ROC) curves and multivariate logistic regression to identify independent risk factors. The mean pre-treatment vitamin D level was 23.45 ± 8.3 ng/mL, with 39.3% (118/300) of patients classified as having vitamin D insufficiency. Patients with vitamin D insufficiency demonstrated significantly higher rates of grade 3-4 sensory CIPN compared to those with sufficient levels (32.2% vs. 5.5%, p < 0.001). Mean vitamin D levels were significantly lower in patients who developed severe CIPN (17.5 ± 4.9 ng/mL vs. 24.6 ± 8.4 ng/mL, p < 0.001). ROC analysis demonstrated vitamin D's predictive value for motor CIPN (AUC = 0.747, p = 0.038). Multivariate logistic regression analysis confirmed vitamin D insufficiency as an independent predictor of sensory CIPN (OR = 6.72, 95% CI: 3.09-14.61, p < 0.001), even after adjusting for age, body mass index, and treatment schedule. Vitamin D insufficiency is independently associated with an increased risk of severe paclitaxel-induced peripheral neuropathy in breast cancer patients. While causal inference cannot be drawn from this observational design, these findings provide a strong rationale for future randomized controlled trials to evaluate whether vitamin D supplementation could serve as a candidate preventive strategy to mitigate CIPN severity and optimize cancer therapy outcomes.