Diabetic foot ulceration represents a prevalent, persistent and resource-intensive complication of diabetes. These ulcers are slow to heal, prone to recurrence and impose a substantial burden on both patients and healthcare providers. The reducing the impact of diabetic foot ulcers (REDUCE) intervention has been designed as a multifaceted approach targeting psychological and behavioural determinants linked to diabetic foot ulcer (DFU) outcomes. Following a successful pilot trial, the REDUCE trial has been designed as a pragmatic, multicentre randomised trial to compare the effectiveness and cost-effectiveness of the REDUCE intervention plus usual care versus usual care alone in reducing recurrence in people with healed DFUs. Additionally, there is an embedded process evaluation and two sub-studies which will be carried out alongside the main trial.

Adults over 18 years of age, with a recently healed DFU and two lower limbs, will be identified from around 30 specialist multidisciplinary diabetic foot clinics at participating National Health Service Trusts in the UK. Patients with active Charcot neuro-osteoarthropathy, active DFU or ulcers healed for more than 12 weeks will be excluded. We will aim to recruit 544 participants (1:1 randomisation). The primary outcome for this trial will be total ulcer-free days with limbs intact (ie, without amputation) between randomisation and the end of follow-up (18 months post-randomisation). Secondary outcomes include time to re-ulceration, total number of ulcers, amputation, quality of life (EQ-5D-5L), Patient Health Questionnaire-9, Nottingham Assessment of Functional Footcare, ICEpop capability measure for adults and resource use. As part of the process evaluation, up to 20 REDUCE intervention patient-participants will be interviewed, and the healthcare professionals delivering the intervention will also be interviewed. An assessment of intervention fidelity will also be carried out.

Ethics approval was granted by Wales 3 Research Ethics Committee (REC reference 22/WA/0053) on 16 March 2022. The findings will be presented at relevant conferences and disseminated via peer-reviewed research publications and to relevant stakeholders.

ISRCTN15570706.

Patients with hypertrophic cardiomyopathy (HCM) and type 2 diabetes (T2D) have a more severe cardiac phenotype and worse clinical course than non‑diabetic patients. To identify how T2D aggravates the disease and whether the most abundant cardiac protein, myosin, is involved, we combined functional, structural and mass spectrometry analyses of human samples.

Left ventricular septal myectomy samples from genotype‑negative (G-) HCM patients without T2D (G- , N = 19) and with T2D (G-T2D, N = 15) were analyzed mainly using fluorescent ATP chase experiments, small‑angle X‑ray diffraction and targeted myosin heavy chain proteomics.

Mant‑ATP chase measurements showed a lower fraction of myosin heads in the energy‑conserving super‑relaxed (SRX) state in G-T2D compared to non-diabetic myocardium. In parallel, X‑ray diffraction showed trends toward structural alterations in myosin organization in G-T2D tissue, consistent with altered OFF/ON state equilibrium. Targeted mass spectrometry identified hyperacetylation of several myosin lysine residues in G-T2D, including K847 within the S2 region. All‑atom molecular dynamics simulations indicated that K847 acetylation disrupts stabilizing electrostatic interactions in the interacting‑heads motif, which is associated with the OFF state.

Disruption of myosin super‑relaxation emerges as a central cellular defect in G-T2D HCM myocardium and can be mechanistically linked to site‑specific myosin hyperacetylation at K847, providing a potential therapeutic target for genotype‑negative HCM with T2D.

To map the scientific landscape linking diabetes mellitus and periodontal disease using bibliometric methods, identify major thematic clusters, and examine how research supports clinical and educational perspectives relevant to integrated diabetes-oral health research. The central research question was: What are the dominant knowledge structures and interdisciplinary connections in the literature on diabetes mellitus and oral health? A bibliometric analysis was conducted using the Web of Science Core Collection (1995-2024). The search strategy combined diabetes related and oral health-related terms. After applying the eligibility criteria, 1,058 publications were included. Keyword preprocessing involved synonym unification, abbreviation harmonization, and manual validation. VOSviewer v1.6.18 was used for keyword co occurrence mapping. Potential sources of bias related to database selection and keyword variability were acknowledged. Eight thematic clusters were identified, covering periodontal disease, prevention, epidemiology, systemic comorbidities, microbiome research, quality of life, clinical interventions, and biomarkers. Cluster structure remained stable across sensitivity thresholds. The literature on diabetes and oral health exhibits recurring thematic patterns and interconnected research domains. While bibliometric clustering reflects co occurrence structures rather than conceptual maturity, the findings provide an analytical overview of how research areas relate to one another. The findings indicate recurring thematic patterns and interconnected research domains. The identified clusters outline priority domains relevant to risk assessment, prevention, and interdisciplinary care. Although bibliometric findings do not directly inform clinical decision making, they highlight areas where integrated diabetes-oral health strategies may be strengthened.

Objective: To establish evidence of the clinical validity of the nursing diagnosis risk for ineffective blood glucose (00489) pattern self-management in patients undergoing hemodialysis. Method: A case-control study was conducted between May and August 2024 at a hospital in northeastern Brazil, involving 60 patients, 30 in the case group and 30 in the control group. An association was considered present when the risk factor, associated condition, or at-risk population had a p-value < 0.05 and an odds ratio > 1. Results: The risk factors insufficient knowledge about the signs and symptoms of hyperglycemia and hypoglycemia and inadequate food intake were prevalent. Conditions associated with diabetes mellitus and the use of high-flux dialyzer filters, an at-risk population characterized by patients with a longer history of diabetes mellitus increased the likelihood of the outcome. Conclusion: Evidence was obtained for the clinical validity of the nursing diagnosis risk for ineffective blood glucose pattern self-management in hemodialysis patients, demonstrating associations with the related conditions and at-risk population. Implications for nursing practice: The findings contribute to advancing discussions in the scientific and healthcare fields by providing evidence on the elements that predispose hemodialysis patients to glycemic alterations.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and newer dual-incretin therapies have become central to the treatment of diabetes mellitus and obesity, with benefits extending beyond glycemic control. Their expanding use has prompted growing interest in their potential ocular effects. Experimental data support plausible protective mechanisms, including reduction in oxidative stress and neuroprotective effects on retinal and optic nerve tissues. Clinical evidence, however, remains heterogeneous. In diabetic retinopathy, the main concern appears to be transient early worsening associated with rapid glycemic improvement rather than direct retinal toxicity. A potential semaglutide-associated signal for non-arteritic anterior ischemic optic neuropathy has raised concern, although the absolute risk appears low and causality remains unproven. Emerging studies also suggest possible beneficial associations with glaucoma, ocular surface diseases, and certain retinal vascular outcomes, whereas the evidence regarding age-related macular degeneration and cataract remains conflicting or preliminary. Overall, ocular outcomes associated with incretin-based therapies seem to reflect a complex interplay among drug-specific pharmacology, systemic metabolic changes, and individual patient susceptibility rather than a class effect. Baseline ophthalmic assessment and individualized follow-up may be advisable in selected high-risk patients. Further prospective ophthalmology-focused studies are needed to clarify long-term safety and identify the patients most likely to benefit or develop adverse events.

Necrotizing fasciitis (NF) is a rapidly progressive, life-threatening soft tissue infection characterized by fascial necrosis, with mortality rates of 20-30%. Despite its rarity, NF is increasingly encountered due to the rising prevalence of predisposing factors. Data from Southern European tertiary centers remain scarce.

We retrospectively reviewed all patients ≥18 years with radiological and/or surgical diagnosis of NF managed at IRCCS Policlinico San Matteo, Pavia, Italy, between November 2018 and August 2023. Clinical, microbiological, and treatment data were extracted from electronic medical records. The Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score was calculated retrospectively. The Charlson Comorbidity Index was computed for each patient. Given the small sample size, we adopted a purely descriptive analytical approach without inferential testing.

Thirteen patients met inclusion criteria (median age 58 years, IQR 44.5-79.5; 69.2% male). The most common comorbidities were diabetes mellitus (6/13, 46.2%), renal failure (4/13, 30.8%), and chronic liver disease (4/13, 30.8%). The age-adjusted Charlson Index ranged from 0 to 11 (median 4). Lower limbs were the most frequently affected anatomic site (5/13, 38.5%), followed by the perineal/genital region (Fournier gangrene, 4/13, 30.8%). Type II (monomicrobial) NF predominated (9/13, 69.2%). Microbiological cultures were positive in 8/13 patients (61.5%): Gram-positive cocci were isolated in 5/8 (62.5%) and mixed aerobic/anaerobic flora in 3/8 (37.5%). Empirical antibiotic regimens included a piperacillin-tazobactam backbone in 6/12 (50.0%) patients and a meropenem-based combination in 5/12 (41.7%); 6/12 patients underwent targeted de-escalation after culture results. Two patients (15.4%) died in hospital, both with Fournier gangrene and Type I infection (mortality 2/4, 50.0% in Type I vs. 0/9 in Type II). The median length of stay was 26 days (IQR 17-28.5). All patients had LRINEC ≥6 at admission, with 9/13 (69.2%) classified as high risk (≥8).

In this small retrospective Italian cohort, NF was most frequently associated with diabetes and high comorbidity burden. Type I (polymicrobial) infections, predominantly involving the perineal region, showed worse outcomes than Type II infections. The clinical experience accumulated during this study period subsequently informed the development of an institutional empirical antimicrobial protocol for skin and soft tissue infections at our hospital.

Older adults with type 2 diabetes mellitus (T2DM) are at high risk of polypharmacy and potentially inappropriate medication (PIM) use because of multimorbidity and complex treatment regimens. This systematic review and meta-analysis (PRISMA 2020; PROSPERO CRD420251149348) aimed to estimate the prevalence of polypharmacy and PIM use, describe PIM burden and patterns, and summarize the co-occurrence of PIMs among those with polypharmacy. On 7 September 2025, we searched PubMed, Scopus, Embase, Web of Science, and MEDLINE using a structured search strategy based on the PICO framework. Observational studies of older adults (≥65 years) with T2DM reporting polypharmacy and PIMs were included. Risk of bias was assessed using the JBI checklist, and prevalence estimates were synthesized using a random-effects meta-analysis. Five studies (13,350 participants) were included. Polypharmacy prevalence ranged from 43.6% to 95.3%, while PIM prevalence ranged from 23.4% to 74%. The co-occurrence of PIMs among polypharmacy users ranged from 39.6% to 74%. Commonly reported PIM classes included long-acting sulfonylureas, proton pump inhibitors, and benzodiazepines. Overall, polypharmacy and PIM use were frequently reported among older adults with T2DM; however, the wide variation in prevalence across studies indicates substantial clinical and methodological heterogeneity. These findings highlight the need for structured medication review and clinical context-based medication optimization beyond numerical thresholds.

Elevated butyrylcholinesterase (BChE) levels are recognized as an indicator of type 2 diabetes mellitus (T2DM), a finding supported by clinical trials. Technologies that utilize BChE as a biomarker for diagnosing T2DM are currently under development, yet few fluorescent probes have been explored in this field. Fluorescence imaging offers several advantages including ease of operation, rapid detection speed, and high sensitivity. Consequently, the development of a fluorescent probe capable of detecting BChE activity for T2DM holds significant importance. However, there is a lack of a specific fluorescent probe to detect the BChE level across multi-models, including cellular systems, zebrafish, and mice with T2DM. Herein, we designed a fluorescent probe that is specifically responsive to BChE, enabling effective detection of changes in BChE levels. The probe demonstrated outstanding sensitivity, specificity, and photostability, with its fluorescence intensity remaining largely unaffected by pH values. The probe effectively detected changes in cellular BChE levels induced by various inducers and successfully identified variations in the abdominal fluorescence signal in zebrafish treated with these inducers. Furthermore, the probe was employed to assess BChE levels in the tissues of the T2DM mouse model. The probe facilitates a deeper understanding of the pathogenesis and progression of T2DM and provides a powerful diagnostic tool for potential therapeutic targets.

To investigate the correlations of various clinical indicators, fibroblast growth factor 23 (FGF23), and Apelin-13 with osteoporosis (OP) and diabetic peripheral neuropathy (DPN) in postmenopausal women with type 2 diabetes mellitus (T2DM), and to evaluate their predictive value for OP and DPN.

A total of 320 postmenopausal women were enrolled, including 238 patients with T2DM and 82 non-diabetic patients with OP. Clinical data, bone metabolism markers, continuous glucose monitoring parameters, Current Perception Threshold (CPT), and Bone Mineral Density (BMD) were collected. Serum levels of FGF23 and Apelin-13 were measured via ELISA. Multivariate regression analyses identified independent factors for BMD, OP, and DPN in T2DM patients. Predictive performance was evaluated using ROC curves. The characteristic clinical phenotype of OP patients with comorbid T2DM was also summarized.

In postmenopausal women with T2DM, 25OH-VitD and Apelin-13 were independently associated with higher T-scores (protective factors), while PTH, CPT scores, and FGF23 were independently associated with lower T-scores (risk factors). Logistic regression revealed that longer DD, elevated superficial peroneal/saphenous nerve CPT scores, and higher FGF23 were independently associated with increased OP risk, while higher E2 and Apelin-13 were independently associated with decreased OP risk. The combined model of these indicators showed an AUC of 0.958 (95% CI: 0.934-0.982) for predicting OP. Logistic regression indicated that a lower BMD T-score was independently associated with increased DPN risk (OR = 0.13, p < 0.001), with a predictive AUC of 0.926 (95% CI: 0.891-0.961). OP patients with T2DM exhibited a more adverse metabolic-bone profile, including higher FGF23 and lower Apelin-13.

In this cross-sectional study, decreased BMD in postmenopausal T2DM women was independently associated with bone metabolism disorders, FGF23/Apelin-13 imbalance, and impaired nerve function. OP and DPN shared long diabetes duration, high FGF23, and low Apelin-13. A model combining DD, E2, CPT, FGF23, and Apelin-13 showed good OP discrimination (AUC = 0.958); BMD T-score discriminated DPN (AUC = 0.926). Both require external validation. These hypothesis-generating findings suggest that FGF23 and Apelin-13 may be potential targets for future research on synergistic OP/DPN prevention and treatment.

Prospective randomized data on sodium-glucose cotransporter-2 inhibitors in kidney transplant recipients with post-transplant diabetes mellitus (PTDM) remain limited.

In this randomized controlled trial, adult kidney transplant recipients with PTDM were assigned to dapagliflozin 10 mg daily plus standard care or standard care alone for 38 weeks. Prespecified primary outcomes were changes in hemoglobin A1c (HbA1c) and estimated glomerular filtration rate (eGFR). Secondary outcomes included fasting plasma glucose (FPG), serum uric acid (UA), urinary albumin-to-creatinine ratio (UACR), renal resistive index (RRI), and safety.

At week 38, between-group differences in HbA1c and eGFR were not statistically significant. Longitudinal analyses across all visits likewise showed no significant between-group differences in HbA1c (P = 0.635) or eGFR trajectories (P = 0.457). Compared with standard care, dapagliflozin was associated with greater reductions in FPG and greater improvement in UA, UACR, and RRI. Exploratory analysis within the dapagliflozin group showed no significant correlation between changes in UACR and HbA1c. Dapagliflozin was generally well tolerated, with no significant between-group differences in adverse events, and tacrolimus trough concentrations remained stable.

In kidney transplant recipients with PTDM, dapagliflozin was generally well tolerated over 38 weeks. Although HbA1c and eGFR did not differ significantly between groups, favorable changes were observed in several secondary and exploratory surrogate measures. These findings are hypothesis-generating and require confirmation in larger blinded trials powered for clinical outcomes.