To investigate whether seasonal alterations and meteorological factors are associated with the incidence of vitreous hemorrhage in patients with proliferative diabetic retinopathy (PDR).

This retrospective observational study included patients with PDR who visited Seoul St. Mary's Hospital between January 2019 and December 2021. Among the 4,402 eyes with PDR, the presence of vitreous hemorrhage was determined. The monthly incidence of vitreous hemorrhage and meteorological data were obtained and analyzed.

Among 4,402 eyes of PDR, vitreous hemorrhage was observed in 293 eyes (6.66%). The incidence of vitreous hemorrhage was high in May (9.37%, 31 of 331 eyes) and June (8.58%, 26 of 303 eyes). Poisson regression analyses revealed that temperature, humidity, and precipitation-per-hour did not influence the risk of vitreous hemorrhage. Thus, the observed seasonal variation in vitreous hemorrhage was not fully explained by the measured meteorological factors. The Wilcoxon signed-rank test revealed a significant difference between the intraocular pressure (IOP) at the time of hemorrhage (hemorrhage-IOP; hot season) and IOP at the visit immediately before the occurrence of hemorrhage (pre-IOP; cold season) groups (P = .029) and between the hemorrhage-IOP (warm season) and pre-IOP (cold season) groups (P = .041).

Vitreous hemorrhage in PDR showed seasonal variations, peaking in May and June. This pattern could not be fully explained by the meteorological variables evaluated; IOP-fluctuations caused by temperature changes and systemic factors such as seasonal changes in glycemic control may contribute to this variability. Further studies are warranted to elucidate the underlying mechanisms.

This study evaluated the effectiveness of web-based educational video module on diabetes knowledge, empowerment, and clinical outcomes among adults with poorly controlled type 2 diabetes in a primary care setting.

A single-centre, parallel-group, randomised controlled trial was conducted at a public primary care clinic in Malaysia. Adults aged 18 years or older with type 2 diabetes for at least six months and poor glycaemic control were randomly assigned to receive either a web-based educational video intervention or standard care. The intervention consisted of culturally adapted, multilingual educational videos covering diabetes self-care, medication use, diet, physical activity, and complication prevention, supported by monthly follow-up reminders. Primary outcomes were diabetes knowledge and empowerment. Secondary outcomes included HbA1C, blood pressure, fasting lipid profile, body mass index, and waist circumference. Outcomes were assessed at baseline, three months, and six months.

A total of 232 participants were randomised into intervention and control groups (n = 116 each), with mean age of 59 years old, slight male predominance (53.0%) and mostly Malay (43.1%), with obesity (51.7%). Following the web-based intervention, participants demonstrated significant improvements in diabetes knowledge (β = 23.74, 95% CI: 20.57-26.91) and empowerment (β = 11.53, 95% CI: 9.98-13.09) compared with those receiving standard care at both three and six months (p < 0.001). Improvements in HbA1C, blood pressure, fasting lipid profile, body mass index, and waist circumference were also observed in the intervention group relative to controls (p < 0.05).

A culturally adapted, web-based educational video module was associated with improvements in diabetes knowledge, empowerment, and cardiometabolic outcomes among adults with poorly controlled type 2 diabetes. These findings support the use of web-based education as a scalable adjunct to standard diabetes care in primary care settings.

Diabetic kidney disease (DKD) is a frequent complication of type 2 diabetes and is closely linked to systemic inflammation. Peripheral blood mononuclear cells (PBMCs) are markers of systemic inflammatory and metabolic stress. It is unknown if metabolism-related transcriptomic alterations in these cells is associated with DKD. Using the nCounter® Human Metabolic Pathways Panel we profiled PBMC metabolic transcripts in individuals with type 2 diabetes or DKD and in controls (n = 12/group), and integrated transcriptomic data with clinical, inflammatory, and mitochondrial parameters. Patients with DKD showed increased inflammatory biomarkers and reduced PBMC mitochondrial membrane potential and mass, consistent with mitochondrial dysfunction. Metabolism-related transcriptomic profiling identified 13 differentially expressed genes across groups. DKD subjects displayed downregulation of SLC7A11 versus controls and HLA-DQA1 versus type 2 diabetes, and upregulation of CPT1A and GBA1 versus controls. CPT1A upregulation was confirmed by RT-qPCR and supported by external GEO datasets, though ROC analyses indicated a limited discriminatory performance. Pathway analyses revealed enrichment of immune-related, fatty acid oxidation, and fructose-6-phosphate pathways and reduced cell proliferation pathways in DKD patients. Inflammatory markers correlated positively with energy-regulating pathways and negatively with anabolic processes. In conclusion, these findings suggest that PBMCs reflect immunometabolic remodeling in response to DKD, thus highlighting an association between systemic inflammation, mitochondrial dysfunction, and altered energy metabolism in circulating immune cells.

The aim of this study was to evaluate the long-term effectiveness of the FreeStyle Libre 2 device in reducing time below range levels 1 (TBR-1) and 2 (TBR-2), compared with the first-generation FreeStyle Libre device without alarms, in people with type 1 diabetes mellitus. A longitudinal observational pre-post study of a single cohort was conducted in a cohort of 93 people with type 1 diabetes mellitus who switched from FreeStyle Libre to FreeStyle Libre 2 in routine clinical practice. At 24 months post-switch, significant improvements were observed in TBR-1 (p = 0.001) and TBR-2 (p < 0.001). A significant direct association was identified between years with diabetes mellitus and change in total basal insulin dose from T0 to T1, with a coefficient of 0.14. Additionally, a significant inverse association was found between annual income and coefficient of variation, with a coefficient of -6.3, as well as between annual income and TBR-2, with a coefficient of -2.45. Switching to a flash glucose monitoring system with alarms was associated with improvements at 24 months in time below range, coefficient of variation, and HbA1c in individuals with type 1 diabetes mellitus.

Despite widespread statin use, atherosclerotic cardiovascular disease remains a leading cause of morbidity and mortality worldwide. Monoclonal antibodies targeting circulating proprotein convertase subtilisin-kexin type 9 (PCSK9) substantially reduce low-density lipoprotein cholesterol (LDL-C) levels and cardiovascular events. However, the requirement for self-administration every 2-4 weeks may limit adherence to treatment. Inclisiran, a first-in-class small interfering ribonucleic acid (siRNA) therapy targeting hepatic PCSK9 production, has several potential advantages over the anti-PCSK9 monoclonal antibodies, principally longer duration of action. To date, however, the efficacy and safety of inclisiran have not been proven in a cardiovascular outcomes trial.

The ORION-4 study is the first large-scale clinical outcomes trial of an siRNA therapy, aiming to assess the efficacy and safety of inclisiran among participants with pre-existing atherosclerotic cardiovascular disease. The primary assessment is an intention-to-treat comparison of the effect of inclisiran sodium 300 mg (equivalent to 284 mg inclisiran), given by subcutaneous injection at randomization, at approximately 3 months and then approximately every 6 months thereafter, on major adverse cardiovascular events (MACE), defined as the composite of coronary death, myocardial infarction, fatal or non-fatal ischaemic stroke, or urgent coronary revascularization. Participants will be followed until the median time since randomization is at least 5 years and at least 1700 participants have a recorded adjudicated MACE. With a planned sample size of ∼15,000 participants, ORION-4 was designed to have >99% power to detect a relative reduction in the primary outcome of about one quarter, while also providing an opportunity to assess efficacy in different subgroups as well as on secondary outcomes of interest.

Between 2019 and 2023 a total of 16,124 participants were randomized in the UK and the US. The mean (SD) age was 70 (8.1) years and 30% were female. At baseline, 78% had a history of coronary heart disease, 22% of ischaemic stroke, 15% of revascularization for peripheral arterial disease, and 23% had diabetes mellitus. 85% were on statin therapy (53% high intensity statin, 29% moderate and 3% low intensity statins). Overall, baseline mean (SD) LDL-C was 96 (32) mg/dL, and was similar among participants on high- and moderate/low-intensity statin regimens (87 (27) mg/dL and 93 (26) mg/dL respectively), with higher levels in those receiving no statin therapy (133 (33) mg/dL). Follow-up will complete during 2026 and results will be available in early 2027.

Inclisiran potentially offers a scalable lipid-lowering treatment, either alone or in combination with other agents. ORION-4 will evaluate the clinical efficacy of inclisiran, and provide a robust assessment of the safety of prolonged use of an siRNA therapeutic.

The GLP-1 receptor agonist semaglutide reduces clinically important kidney outcomes in people with type 2 diabetes and chronic kidney disease (CKD). We aimed to assess the pooled effects of semaglutide on kidney outcomes in prespecified analyses of participant-level data from the diverse populations of the SELECT, FLOW, and SOUL randomised placebo-controlled trials.

Participants with CKD (FLOW) or atherosclerotic cardiovascular disease (SELECT and SOUL) were randomly assigned semaglutide (once-weekly subcutaneous 1·0 mg [FLOW], once-weekly subcutaneous 2·4 mg [SELECT], or once-daily oral 14 mg [SOUL]) or matching placebo, added to standard of care. The primary outcome in this pooled analysis was time to first occurrence of a kidney composite, defined as onset of persistent 50% or greater reduction in estimated glomerular filtration rate (eGFR), kidney failure (persistent eGFR <15 mL/min per 1·73 m², or initiation of kidney replacement therapy), kidney-related death, or cardiovascular-related death. Safety was also assessed.

The pooled participants from the trials (N=30 787) had a mean follow-up of 39·5-47·5 months. Among participants assigned to semaglutide, 973 first events of the primary kidney composite occurred compared with 1134 first events for placebo (hazard ratio [HR] 0·84 [95% CI 0·77-0·91]). First events of a narrower secondary kidney composite (excluding cardiovascular-related death from the primary outcome) were also reduced with semaglutide versus placebo (347 and 416, respectively; 0·80 [0·69-0·92]). Safety outcomes were overall similar between groups, and in line with other GLP-1 receptor agonist trials. Serious adverse events were numberically lower with semaglutide than with placebo.

Data pooled from three large phase 3 trials suggest that semaglutide reduces the risk of major kidney outcomes in a broad population with cardio-kidney-metabolic disease while having a favourable risk-benefit profile. In people with cardio-kidney-metabolic disease, with and without diabetes, semaglutide (oral or injected) prevents kidney-related and cardiovascular complications and induces adverse events in line with GLP-1 receptor agonist studies, regardless of baseline characteristics within the cardio-kidney-metabolic spectrum. This was a participant-level analysis conducted in a large database of three randomised controlled trials of similar design and examining the same treatment, but there were some differences in participants' baseline characteristics, and in the dose and route of administration of treatment. This pooled analysis adds evidence for the benefit of GLP-1 receptor agonists in general, and semaglutide in particular, in a broad population of people with cardio-kidney-metabolic disease, suggesting that the benefit of semaglutide might not be explained only by its glycaemic effects, weight-management effects, or both.

Novo Nordisk.

To conduct a scoping review of the application of ecological momentary assessment (EMA) in adolescents with type 1 diabetes (T1DM), providing references for future research and practice in this field.

This review followed the JBI scoping review methodology framework and systematically searched 10 databases, including CNKI, Wanfang, VIP, CBM, PubMed, Web of Science, Cochrane Library, EMbase, PsycINFO and CINAHL, from the establishment of the databases to 29 September 2025. The included literature was summarised and analysed.

Sixteen studies were included. EMA was used to investigate self-management, glycaemic control, psychosocial factors and cognitive function in adolescents with T1DM. Key findings revealed dynamic, real-time associations: self-management behaviours showed time- and context-dependent effects on glycaemic control (e.g. higher risk of omissions in mornings or social situations); affect and glucose levels exhibited bidirectional interactions, with negative affect impairing and positive affect improving glycaemic stability; social environment (peer and family support) and cognitive function (e.g. executive function) significantly moderated management outcomes. Most identified associations were within-person and contemporaneous; few studies examined between-person differences or time-lagged predictive effects. EMA demonstrated acceptable feasibility across diverse protocols. However, considerable methodological heterogeneity existed across studies, and most evidence was limited to Western populations.

EMA is a feasible method for managing type 1 diabetes in adolescents and is capable of capturing real-time, dynamic associations among behaviour, affect, social context and glycaemic control. Future research should prioritise methodological standardisation, develop culturally adapted assessment tools and explore real-time intervention strategies to enable precise and personalised diabetes management. From a clinical perspective, EMA can guide individualised care by identifying high-risk time windows (e.g. mornings), social contexts (e.g. peer dining) and emotional triggers (e.g. negative affect), supporting targeted patient education, just-in-time behavioural reminders and collaborative mental health interventions.

Chronic kidney disease (CKD) is associated with a higher risk of sepsis and poorer clinical outcomes compared to the general population. While GLP-1 receptor agonists (GLP-1RA) may confer protective effects against sepsis beyond their metabolic benefits in patients with diabetes, their effect in CKD patients remains unclear. This study aims to evaluate the association between GLP-1RA therapy and infectious outcomes in patients with CKD.

Using the TriNetX database, we conducted a retrospective cohort study of adults with CKD and type 2 diabetes mellitus initiating GLP-1RAs or dipeptidyl peptidase-4 inhibitors (DPP-4i) between January 2020 and May 2026. The primary outcome was sepsis. Secondary outcomes included all-cause mortality, septic shock, pneumonia, urinary tract infection, and COVID-19.

After propensity score matching, 21 035 patients were included in each treatment group. Use of GLP-1RA was associated with a lower risk of sepsis compared with DPP-4i (HR = 0.72; 95% CI, 0.66-0.78). GLP-1RA use was also associated with lower risks of all-cause mortality (HR = 0.65; 95% CI, 0.61-0.70), pneumonia (HR = 0.81; 95% CI, 0.75-0.87), urinary tract infection (HR = 0.83; 95% CI, 0.79-0.88), and COVID-19 (HR = 0.84; 95% CI, 0.77-0.90). The risk of septic shock did not reach Bonferroni-corrected significance level despite being numerically lower (HR = 0.84; 95% CI, 0.73-0.96; P = 0.014).

In patients with CKD and type 2 diabetes mellitus, use of GLP-1RA is associated with lower risks of sepsis, all-cause mortality, pneumonia, urinary tract infection, and COVID-19 compared with DPP-4i, while the risk of septic shock was similar between groups.

Diabetic retinopathy (DR), a common microvascular complication of diabetes mellitus, has been associated with ferroptosis-related pathological mechanisms. Evidence indicates that ferroptosis may contribute to retinal injury and disease progression. The present analysis aimed to characterize ferroptosis-associated cell subsets and their roles in the progression of DR.

Single-cell RNA sequencing data derived from diabetic rat models of DR were obtained from the Gene Expression Omnibus database. A total of 464 ferroptosis-related genes were used to calculate ferroptosis scores. Data processing and analysis were performed using the Seurat R package, with differentially expressed genes identified via the FindAllMarkers function. Functional enrichment analyses were conducted using the clusterProfiler package. Protein-protein interaction networks were constructed using the STRING database, and intercellular communication was predicted using CellChat. Key findings were validated through reverse transcription quantitative polymerase chain reaction (RT-qPCR).

Cell clustering identified nine principal retinal cell types. Compared with normal control groups, the DR group demonstrated altered proportions of Müller cells, vascular endothelial cells, microglia, and cone photoreceptor cells. Ferroptosis-score-related differences were most evident in Müller cells and rod cells. In the revised WT-baseline sensitivity analysis, the high-ratio ferroptosis-score cell distribution remained significantly altered in Rod and Müller cells after multiple-testing correction.

This study identified key ferroptosis-associated retinal cell populations, with an emphasis on the functional roles of ferroptosis-associated Müller cell subsets in the context of DR. These findings provide further insight into the cellular mechanisms underlying DR and highlight potential molecular targets for therapeutic intervention.

Adiposity increases the risk of post-menopausal oestrogen receptor (ER)-positive breast cancer. Inflammation, insulin, and insulin-like growth factors and sex-steroid hormones may explain this effect. We performed interventional mediation analysis to estimate the effects of hypothetical interventions targeting these pathways in females with obesity on reducing their excess risk of post-menopausal ER-positive breast cancer relative to females with normal weight.

The mediation analysis included 1260 post-menopausal females (352 with ER-positive breast cancer) from a case-cohort within the Melbourne Collaborative Cohort Study. A Monte Carlo g-computation approach with non-parametric bootstrapping was used to estimate the risk differences (RDs) and 95% confidence intervals (CIs) for interventional direct and indirect effects of hypothetical interventions that shift the joint distribution of inflammation, insulin, and sex-steroid hormone biomarkers in females with obesity to the levels observed in females with normal weight.

The estimated RD for the total effect of obesity relative to normal weight on post-menopausal ER-positive breast cancer was 16.1 (95% CI: 3.3, 30.4) per 1000 females. The RDs for indirect effects through inflammation, insulin, and sex-steroid hormones were 16.4 (95% CI: 4.3, 27.2), -8.4 (95% CI: -23.4, 1.2), and 13.0 (95% CI: 3.3, 23.7) per 1000 females, respectively. The - RD for the direct effect not via any of these three pathways was -5.3 (95% CI: -17.4, 10.6) per 1000 females.

Inflammation and sex-steroid hormones, but not insulin, contributed to the detrimental effect of adiposity on the risk of post-menopausal ER-positive breast cancer. Interventions targeting these pathways may reduce the risk for females with obesity.