Topical insulin improves postoperative wound healing in controlled diabetic patients through regulating the expression of E-Cadherin and Ki67: an open-label randomized controlled-trial

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Abstract
Background: Diabetic patients are at a significantly higher risk of delayed and impaired wound healing, with increased susceptibility to wound infections and dehiscence. The pathophysiology of abnormal wound healing in diabetes is multifactorial, involving impaired vascularization, reduced cellular proliferation, and prolonged inflammation, all associated with hyperglycemia. This randomized controlled trial (ClinicalTrials.gov registration: NCT06400082) included 74 type 2 diabetic patients undergoing elective abdominal surgeries with wound lengths ≥ 10 cm. Patients were randomized into two equal groups to receive either topical saline dressings or topical regular insulin. Wound dressing and assessments were performed daily until complete closure. Outcomes included percentage reduction in wound surface area, healing days, and unit healing time (UHT). Skin sections were collected on days 0 and 7 to evaluate e-cadherin, Ki67, IL-6, 8-hydroxy-2’-deoxyguanosine (8-OHdG), and histological architecture. Results: Topical insulin significantly enhanced wound healing outcomes, demonstrating a greater percentage reduction in wound surface area (p < 0.001) and a lower UHT at day 7 in the insulin group (4450.00 [3000.00–5460.00]) compared to the saline group (2594.00 [2090.00–7560.00]), p = 0.001). Insulin-treated wounds exhibited increased tissue expression of collagen, e-cadherin, and Ki67, along with significantly reduced levels of IL-6 and 8-OHdG (p < 0.05). Conclusion: Topical insulin is a promising therapeutic strategy for improving postoperative wound healing in diabetic patients. It enhances tissue repair by modulating inflammation, oxidative stress, and cellular proliferation.

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