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A lack of murine models that mimic impaired wound healing in people with type 2 diabetes has hindered research. The commonly used leptin-receptor knockout model (db/db) fails to accurately reflect the pathophysiology of human disease. This study aimed: (i) to investigate whether our novel murine model of diabetes, whilst less hyperglycaemic and obese than db/dbs, effectively demonstrated impaired wound healing, and (ii) to identify the most robust methods for quantifying wound closure. C57BL/6J mice were high-fat diet fed for a total of 11 weeks and injected with three doses of streptozotocin (65 mg/kg body weight) at week 5 with chow-fed mice as controls. All mice received four excisional wounds and were euthanised at day-4 or day-10 post-wounding (n = 8/group/timepoint). Wound healing was evaluated by digital planimetry, histology, Micro-CT, and tensiometry. Histological analysis was the most sensitive method for identifying impaired wound healing. Our high-fat diet/low-dose streptozotocin model had significantly higher non-fasting blood glucose (25.7 ± 5.4 mmol/L vs. 8.7 ± 0.8 mmol/L) and lower wound quality scores (day-4 post-wounding: 2.6 ± 1.9 vs. 4.4 ± 0.8) than healthy controls (both p < 0.05). At day-10 post-wounding, a linear trend in wound healing was observed between healthy controls, our novel model and the db/db model, indicating that our diabetic murine model may be clinically relevant for studying diabetes-related wound healing.
Cystic fibrosis-related diabetes (CFRD) is one of the most clinically impactful comorbidities associated with cystic fibrosis (CF). Current recommended management with insulin therapy is challenging due to variable daily insulin requirements and adds to the significant burden of self-management. This study aims to determine if hybrid closed-loop insulin delivery can improve glucose outcomes compared with standard insulin therapy with continuous glucose monitoring (CGM) in young people (≥16 years) and adults with CFRD.
This open-label, multicentre, randomised, two-arm, single-period parallel design study aims to randomise 114 young people (≥16 years) and adults with CFRD. Following a 2–3 weeks’ run-in period, during which time participants use a masked CGM, participants with time in target glucose range (3.9–10.0 mmol/L) 10.0 mmol/L), mean glucose and HbA1c. Other secondary efficacy outcomes include glucose and insulin metrics, change in forced expiratory volume in 1 s and body mass index. Safety, utility, participant experiences and participant-reported outcome measures will also be evaluated. The trial is funded by the National Institute for Health and Care Research.
Ethics approval has been obtained from East of England–Cambridge South Research Ethics Committee. Results will be disseminated by peer-reviewed publications and conference presentations, and findings will be shared with people living with CF, healthcare providers and relevant stakeholders.
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