Type 2 diabetes mellitus (T2D) is a pervasive metabolic disorder driven by insulin resistance and progressive pancreatic β-cell failure, with a rapidly growing global prevalence. Its pathogenesis now extends beyond hyperglycemia to encompass intricate immunometabolic dysregulation, mitochondrial dysfunction, and organelle stress. However, a cohesive synthesis that integrates these disparate molecular mechanisms with contemporary therapeutic advancements remains missing. This review systematically investigates the immunometabolic axis, highlighting macrophage polarization and exosomes, as well as nanotube-mediated crosstalk with β-cells, and describes how mitochondrial dynamics disorder and impaired mitophagy become the core driving factors for β-cell failure. Lipotoxicity mediated by ceramides, diacylglycerols, and cholesterol imbalance is critically analyzed alongside proteotoxicity from islet amyloid polypeptide aggregation. We then chart the therapeutic evolution from glucocentric strategies to modern complication-centric paradigms, emphasizing SGLT2 inhibitors and GLP-1 receptor agonists that confer proven cardio-renal protection. Personalized treatment, multiomics integration, next-generation precision therapies, and holistic art-based interventions that promote sustainable lifestyle changes are further discussed. By connecting molecular insights to clinical application, this review provides a comprehensive resource for researchers and clinicians, aiming to advance T2D management and improve global patient outcomes.

Sepsis-associated acute kidney injury (SA-AKI) raises mortality risk, while the independent links of pre-existing diabetes mellitus (DM) and in-hospital glycemic status to SA-AKI remain unclear. This study explored their correlations with early SA-AKI among sepsis patients.

This multicenter retrospective cohort enrolled 6,974 pathogen-positive adult sepsis patients admitted to ICUs from 2023 to 2026. We used pre-existing DM as the primary exposure and time-weighted average glucose as the secondary marker. Multiple adjustment methods including propensity score matching (PSM) and inverse probability weighting (IPW) were adopted to reduce confounding bias.

After enrolling 6,947 septic ICU patients, multivariate logistic regression identified pre-existing DM as an independent risk factor for early SA-AKI (adjusted OR = 2.54, 95% CI 2.25-2.86, p < 0.001). The protective glycemic range was 6-11 mmol/L for diabetic patients (adjusted OR = 0.88, 95% CI 0.78-0.98, p = 0.025) and 8-13 mmol/L for non-diabetic patients (adjusted OR = 0.55, 95% CI 0.48-0.62, p < 0.001). PSM, IPW and doubly robust estimation all validated these consistent associations. Abnormal glucose showed weak predictive power for SA-AKI (AUC 0.60-0.61). Higher time-weighted glucose correlated with advanced AKI stages and increased in-hospital mortality in mild-to-moderate SA-AKI patients. Diabetic SA-AKI patients had higher proportions of stage 1 and stage 3 AKI without significant difference in overall in-hospital mortality compared with non-diabetic counterparts. Matched SA-AKI patients suffered longer ICU/hospital stays, more organ support use and higher hospital mortality.

Common pathogenic organisms had higher detection rates in SA-AKI cases. Pre-existing DM was positively correlated with early SA-AKI. Targeted in-hospital glycemic intervals were linked to lower SA-AKI risk, which supports individualized glucose monitoring for sepsis patients.

A domestic longhair cat in Australia was referred to an ophthalmology service with the complaint of lens opacity. An incipient cataract was diagnosed in the right eye and an intumescent cataract with an equatorial lens capsule rupture in the left eye. The patient was being treated for diabetes mellitus, and previous concerns for the eyes had included conjunctivitis and left-sided periocular swelling and epiphora. Systemic work-up performed over the 7 months before ophthalmic referral included complete blood counts, biochemistry, serology (feline immunodeficiency virus, feline leukaemia virus, toxoplasmosis, cryptococcosis), thoracic radiographs, and ocular ultrasound and electroretinography performed before phacoemulsification. The patient did not have evidence of active uveitis at the initial ophthalmological examination, and historical serology excluded some common infectious causes of uveitis. The cataracts were treated successfully by phacoemulsification in both eyes, restoring vision. However, an intraocular lens was implanted only in the right eye, as the pre-existing lens capsule tear in the left eye precluded intraocular lens placement. Based on the medical history and clinical presentation, diabetes mellitus was suspected to be the cause of the cataracts.

Intumescent cataracts are reported in humans and dogs but have rarely been reported in domestic cats. Nonetheless, the intumescent cataract in this patient had similar characteristics to those in diabetic canine cataracts.

Long-chain omega-3 fatty acids (FAs) and vitamin D (VitD) are implicated in the modulation of immune responses and inflammatory processes within the body. The COMED study evaluated levels of DHA, EPA and DPA (expressed as a modified omega-3 index, mO3I, defined as the percentage of these FAs relative to total FAs in whole blood) and VitD in patients with COVID-19 in relation to mortality and severe disease, as well as additional morbidity-related outcomes, including probability of hospitalisation and length of hospital stay (LOS).

A total of 160 patients were enrolled, of whom 28 died during follow-up. Associations between mO3I and VitD levels and clinical outcomes were analysed using logistic and linear regression models adjusted for age, sex, BMI, smoking, diabetes mellitus, and hypertension.

Higher mO3I levels (Q4 ≥ 6.39%) were associated with lower odds of death (OR = 0.24, 95% CI: 0.05-0.87) and lower probability of hospitalisation (OR = 0.28, 95% CI: 0.09-0.91) compared with lower mO3I levels (Q1-Q3). Higher VitD levels (Q4 ≥ 71.9 nmol/L) were associated with a shorter LOS by 2.19 days compared with Q1-Q3, while higher levels (Q2-Q4 > 36.7 nmol/L) shortened LOS by 2.96 days compared with Q1. Age was the strongest predictor of mortality, severe disease, and LOS; BMI increased the probability of severe disease; smoking prolonged LOS.

Higher mO3I levels were associated with lower odds of death, with similar trends observed for hospitalisation, whereas higher VitD levels were associated with a shorter LOS. Nutritional biomarkers and modifiable lifestyle factors, such as body weight and smoking, were associated with differences in clinical outcomes in COVID-19. However, the observational design of the study precludes causal interpretations.

Comparison of percentage total body weight loss (%TWL) between metabolic bariatric surgery and incretin-based pharmacotherapy in adults with type 2 diabetes mellitus. Forest plot showing pooled mean difference in percentage total body weight loss (%TWL) between treatment groups. Positive values favor metabolic bariatric surgery. Random-effects model with Hartung-Knapp adjustment was used.

Concentration of circulating soluble tumor necrosis factor receptor 1 is associated with faster progression in patients with diabetic kidney disease based on data obtained from large longitudinal cohort studies. A cutpoint of 4.3 ng/mL baseline plasma concentration was identified to stratify patients and predict clinical outcome. We set out to test the prognostic utility of this cutpoint in a randomized clinical trial.

Soluble tumor necrosis factor receptor 1 concentration was measured across plasma samples from Joslin cohort and selonsertib trial cohort. Estimated glomerular filtration rate slope was calculated using a patient-specific linear regression model based on serum creatinine concentration and compared between the cohorts. Kidney-related events were plotted using Kaplan-Meier estimates for both cohorts.

Participants from both the clinical study cohort and the observational cohort showed an inverse relationship between baseline plasma concentrations of tumor necrosis factor receptor 1 and estimated glomerular filtration rate. When stratified based on baseline soluble tumor necrosis factor receptor 1 cutpoint, higher probability of experiencing a clinical event was found in patients with levels of soluble tumor necrosis factor receptor 1 exceeding 4.3 ng/mL in either of the cohorts.

We demonstrated the prognostic utility of plasma concentrations of circulating soluble tumor necrosis factor receptor 1 in identifying individuals with diabetic kidney disease at an elevated risk of progressive kidney function decline in a randomized clinical study setting. This data supports previous findings from large observational cohorts and supports the use of this marker as a reliable predictor of disease outcome.

Diabetic hepatic injury is a common complication of diabetes, yet it is often neglected due to its subtle early symptoms. This study explored the effect and mechanism of Anaphalis virgata extract (AVE) in treating diabetic hepatic injury. Serum-exposed components of AVE were identified by LC-MS and used for network pharmacology to predict therapeutic targets and pathways. AVE was evaluated in diabetic rats treated intragastrically at 50, 100, and 200 mg/kg for 10 weeks. Hepatic biochemical parameters were measured, and mechanisms were verified by molecular dynamics (MD) simulation, ELISA, and Western blot. Thirty-one serum-exposed compounds (8 prototypes and 23 metabolites) were identified, primarily flavonoids, phenolic acids, terpenoids, and phenylpropanoids. Network pharmacology revealed pathways including lipid and atherosclerosis, IL-17, and AGE-RAGE signaling. Apigenin, kaempferol, and caffeic acid were identified as core compounds, and IL-6, TNF, and IL-1β as core targets. In vivo, AVE significantly decreased hepatic IL-6, TNF, IL-1β, TC, TG, FFA, AST, and ALT levels in diabetic rats. Western blot showed that AVE up-regulated AKT and AMPK while down-regulating NF-κB and GSK-3β pathways. AVE exerts a therapeutic effect on diabetic hepatic injury through anti-inflammatory mechanisms, providing a foundation for its further development and clinical application.

Perioperative corticosteroids, particularly dexamethasone, have become a widely adopted component of multimodal pain management in total knee arthroplasty (TKA). While clinical practice guidelines strongly recommend their use, detailed guidance on optimal dosing, frequency, and safety in special populations, especially patients with diabetes mellitus, is still limited.

This narrative review synthesizes the current evidence on systemic perioperative dexamethasone use in TKA, focusing on clinical questions: agent and route selection, dose optimization, dosing frequency, and safety, including considerations for patients with diabetes. A literature search of PubMed, EMBASE, and the Cochrane Library was conducted for studies published between January 2015 and April 2026. Randomized controlled trials, systematic reviews, meta-analyses, clinical practice guidelines, and observational studies addressing systemic corticosteroid use in primary TKA were included. Recent evidence supports intravenous (IV) dexamethasone as the most commonly studied and clinically practical systemic agent. A 16 mg dose provides greater early analgesic and antiemetic benefit than lower doses, and repeat dosing through postoperative day (POD) 1 is supported, with extension to POD 2 emerging but not yet definitive. Perioperative dexamethasone has not been associated with increased infection or wound complications. In patients with well-controlled diabetes, it appears safe with appropriate glycemic monitoring, although safety data are largely limited to doses of 8-10 mg.

Current evidence supports IV dexamethasone as an effective component of multimodal analgesia after TKA. In the general TKA population, 16 mg appears more effective than lower doses for early postoperative pain, opioid consumption, and postoperative nausea and vomiting (PONV)-related outcomes. Repeat dosing through POD 1 is supported by available evidence, whereas extension to POD 2 remains promising but requires further validation. In patients with well-controlled diabetes, perioperative dexamethasone appears safe with appropriate glycemic monitoring, although safety data are largely limited to doses of 8-10 mg, and the safety of the 16 mg dose in this population remains insufficiently defined.

Cerebral sinus vein thrombosis (SVT) is a feared complication of brain tumour surgery, especially in sinus adjacent locations. In the comprehensive treatment of brain metastases (BM) intraoperative radiotherapy (IORT) is recently being established as a safe alternative to postoperative adjuvant stereotactic radiosurgery (SRS). However, uncertainty of on the risk about SVT keeps surgeons reluctant to its use in sinus adjacent locations. Aim of this study is to investigate the risk of SVT in patients undergoing IORT compared to standard postoperative SRS.

We performed a retrospective analysis of 166 patients undergoing resection for histologically confirmed BM, of which 71 (42.8%) received IORT and 95 (57.2%) postoperative SRS. Tumour location, proximity to major dural venous sinuses, presence of SVT on postoperative imaging, timing of postoperative imaging, and, in SRS patients, time from surgery to radiotherapy were analyzed.

Postoperative SVT occurred in 5 patients (3.0%). There was no significant difference in SVT rates in the IORT (n = 2, 2.8%) and SRS (n = 3, 3.2%) groups (p = 1.0). All SVT cases occurred in sinus-adjacent lesions and remained clinically asymptomatic. Time to postoperative imaging did not differ in the two treatment groups. Time to imaging and, for the SRS group, time to radiation therapy, did not differ between the thrombosis and non-thrombosis groups (Mann-Whitney U = 3289.5, Z = - 0.283, p = 0.777 and Mann-Whitney U = 100.0, p = 0.419 respectively).

IORT was not associated with increased risk for SVT compared to surgery with post-operative SRS.

Despite major advances inimmunotherapy, pancreatic ductal adenocarcinoma (PDAC) remains one of the most immunotherapy-resistant solid tumors. This review aims to summarize the key biological mechanisms underlying immune resistance in PDAC and to evaluate established and emerging biomarkers that may guide immunotherapy strategies.

Resistance to immunotherapy in PDAC arises from the interplay of tumor-intrinsic oncogenic signaling, low antigenicity, defective antigen presentation, and a profoundly immunosuppressive tumor microenvironment characterized by dense desmoplasia, hypovascularity, metabolic competition, and enrichment of regulatory T-cells, myeloid-derived suppressor cells, tumor-associated macrophages, and cancer-associated fibroblasts. While MSI-H/dMMR and high tumor mutational burden identify small subsets of patients who may benefit from immune checkpoint blockade, most other biomarkers, including PD-L1 expression, homologous recombination deficiency, KRAS-related immune phenotypes, and circulating markers such as ctDNA and exosomal PD-L1, remain investigational or primarily prognostic. Emerging data highlight the importance of transcriptomic, spatial, and composite biomarker approaches to better capture tumor-immune interactions. PDAC exhibits a complex and actively maintained state of immune resistance that cannot be overcome by checkpoint inhibition alone. Future progress will depend on biomarker-guided combination strategies targeting oncogenic pathways, stromal barriers, and innate immune suppression, along with prospective validation of integrated, multimodal biomarker models to advance precision immuno-oncology in PDAC.