Role of topical insulin therapy in amputation stump

Wound healing is a complex process with overlapping steps of haemostasis, the inflammatory and proliferative phases, remodelling .Any problem with the edge of the wound can be detrimental to healing and may cause delay in wound healing. In this article, we share our experience of using topical insulin therapy for wound bed preparation in non-healing ulcer over the amputation stump.


Introduction
Wound bed preparation is a new concept and is done using the T.I.M.E method. The Edge is a component that involves granulation tissue for better healing. Recently we have come across the application of topical insulin therapy for the management of non-healing ulcer, and we share our experience. Materials and methods: This study was conducted in the department of Plastic Surgery at tertiary care center after obtaining the departmental ethical committee approval. Informed written consent was taken from patient in study .The details of the patient in study are as follows: 37 year old female with no known co morbidities with h/o road traffic accident 4 months back and underwent right below knee amputation due to vascular injury and degloving injury of the left lower limb for Which serial debridement was done in cardiothoracic and general surgery department. Now, the patient presented to plastic surgery department with extensive raw area over the left lower limb and non-healing ulcer over the right below knee amputation stump.

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The regular dressings and antibiotic changes did not lead to wound healing. Wound bed preparation was done using the patient with topical insulin therapy (figure 2).

Figure2
: topical insulin therapy given to the amputation stump 0.1ml of regular insulin was injected or sprayed onto 1cm 2 of the wound when the regular dressing was performed (figure 3). This was repeated once every 3-5 days when the dressing was changed. The wound was reassessed after 2weeks for evidence of wound healing. The wound showed healing as evidenced by healthy granulation tissue. (figure3)

Discussion
Wound bed preparation was redefined as 'the global management of the wound to accelerate endogenous healing or to facilitate the effectiveness of other therapeutic measures. Wound bed preparation started to be summarized by the acronym T.I.M.E with T for tissue: non-viable or deficient. I for infection/inflammation, M for moisture balance. E for epidermis which was later changed to E for edge. Debridement, control of inflammation and moisture are essential parts of wound bed preparation that may stimulate the edge of the wound to migrate, but if they fail, advanced therapies may be required.
Many therapeutic methods are available to effect the wound healing such as the topical application of insulin, growth factors, negative pressure assisted wound closure, oxidized regenerated cellulose/collagen, hyaluronic acid conjugated with glycidyl methacrylate or gelatin dressings.
Role of topical insulin in wound healing has appeared in literature since 1970s [1] . Studies done have found that topical Insulin therapy exerts its effects through the IGF 1 receptor. Insulin is known to stimulate keratinocytes and endothelial proliferation leading to a faster neovascularization as well as formation of granulation tissue [2] . Topical insulin application rapidly induces up regulation of the insulin related proteins on wound areas following injury. IRS-1 binds the PI3-kinase, through the multiple tyrosine phosphorylated sites [3,4] .
Insulin triggers keratinocyte migration depending on the dose and time in the chronic wounds. Insulin demonstrates its effect by an insulin receptor dependent but EGF/EGF-R non-dependent way. It increases the keratinocyte migration on the PI3K-Akt-Rac1 pathway, cause stimulation of keratinocytes by enabling the production of α3 and LN332 molecules is proved in vitro studies [6,7,8,9] . Insulin is a hormone that also has effect on collagen production. Insulin selectively and strongly stimulates the collagen production in dermal fibroblasts [10,11] .The cost of insulin ranges from 130-500 INR per vial.

Conclusion
Topical insulin therapy was found to be useful in management of nonhealing ulcer as it improved the granulation tissue. Long-term clinical observations are needed to determine whether topical insulin can be used for wound bed preparation.

Limitations
This was done on a single patient and needs large population based study to apply the finding in clinical practice.