SLR - April 2019 - Sara M. Davis

Effects of Local Use of Insulin of Wound Healing in Nondiabetic Patients

Reference: Effects of local use of insulin on wound healing in nondiabetic patients. Martinez-Jimenez MA, Valadez-Castillo FJ, Aguilar-Garcia J, Ramirez-GarciaLuna JL, Gaitan-Gaona FL, Pierdant-Perez M, Valdes-Rodriguez R, Sanchez-Aguilar JM. Plastic Surgery (Oakv). 2018 May;26 (2): 75–79. doi: 10.1177/2292550317740688. Epb 2017 Nov 22.

Scientific Literature Review

Reviewed by: Sara M. Davis, DPM
Residency Program: Long Beach Memorial Medical Center

Podiatric Relevance: This article is of relevance to the podiatric surgeon because even though the majority of the wounds we treat are in adults with diabetes, we also treat wounds in those without diabetes. Insulin has been known to have clinical benefits on wounds. Previous clinical trials have shown positive effects of local insulin therapy on diabetic wounds. This paper is of particular interest because it looks to see if there are similar results with the application of insulin to wounds in adults without diabetes. The thought behind this article is that because insulin stimulates healing by increasing blood flow, then the application of it on nondiabetic wounds should have the same effect as it does on the diabetic wounds.

Methods: This was a randomized, split-plot, double-blinded, placebo-controlled trial with 10 nondiabetic patients with full-thickness acute wounds. All of the patients were recruited from the emergency room and were between the ages of 18 and 65, with full-thickness wounds > 40 cm, and were nondiabetic without history of PAD, collagen diseases or any type of renal or hepatic failure. Wounds were located on the upper extremities, lower extremities or sacrum. Each wound was separated equally into two different zones; one zone received standard care plus injection of 0.1 mL of insulin and the other was the control side that received standard care plus injection of 0.1 mL of saline solution. After 14 days, an autologous skin graft was applied to all of the wounds regardless of the trial result. Biopsies were also then taken from both zones on days 0 and 14. The amount of angiogenesis and percentage of fibrosis was evaluated for each zone.

Results: At the start of the experiment, it was found that there was no significant difference between the blood vessels and fibrosis in the control group versus the insulin group (p-value = 0.90). A significant difference was found in the amount of new blood vessels observed on the insulin treatment side compared to the control group side (p-value = 0.04). No significant difference was found between the percentages of fibrosis in the control group versus the insulin group (p-value = 0.40).

Conclusion: This study showed a significant difference in the amount of angiogenesis seen in the insulin treatment zone compared to the saline treatment zone, suggesting insulin may increase blood flow to the wound bed. Insulin did not create fibrosis during wound healing. An increase in blood vessel growth may lead to improved healing time, but this was not evaluated within this current study. Future studies should now focus on the mechanism of action, appropriate dosing and optimal route of delivery of insulin due to the current study only looking at a single dose of 10 units of insulin. Insulin use in wound care looks to have a promising future in our field and could be a source of cost savings if shorter treatment duration is shown in future studies.

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