SLR - June 2017 - Tyler C. Floyd

Effect of Local Insulin Injection on Wound Vascularization in Patients with Diabetic Foot Ulcers

Zhang Z, Lv L. Effect of Local Insulin Injection on Wound Vascularization in Patients with Diabetic Foot Ulcers. Exp Ther Med. 2016 Feb; 11(2): 397–402.

Reviewed By: Tyler C. Floyd, DPM
Residency Program: Bethesda Memorial Hospital, Boynton Beach, FL

Podiatric Relevance: A common condition seen and treated by foot and ankle surgeons is diabetic foot ulcerations. Insulin has been thought to help heal wounds in past studies, but its actual efficacy and systemic effects have not been thoroughly evaluated. This study evaluates the effect of insulin injected directly into the diabetic wound at half of normal dose to increase angiogenesis leading to increased granulation tissue. Increased granulation tissue means increased rates of wound healing therefore, decreasing patient morbidity and mortality, which is beneficial for all parties involved. This study evaluates 32 patients with diabetic foot ulcers; 18 of the patients receive insulin injection and 14 receive a placebo.

Methods: A level 1 randomized control study was performed on 32 patients with diabetic ulceration that had been present from 12 to 160 days with the duration of diabetes ranging from five to 20 years. Patients were enrolled randomly either into the insulin group (n=18) or the control group (n=14). The insulin group injected one-half calculated dose of 30:70 insulin diluted with saline directly into the wound bed and then injected the remainder of their insulin dose in the abdomen as usual. The control group did placebo. Both groups did injections of wounds twice daily for twelve days. On day zero, five, seven and 12 tissue samples were obtained. These samples were then evaluated for CD-34 using CD-34 antibodies. Due to its high predilection in angiogenesis therefore granulation tissue. Also calculated the MVD from the data. Blood glucose levels were monitored at 0.5, 1.0, 2.0 and 4.0 h after injections each day.

Results: Local insulin injection in the wound had marked effect on the systemic blood glucose levels. Showed notable decrease one to two hours after the injection and gradually returned to preinjection level at four hours after injection. Therefore, demonstrating that local wound injection of insulin could achieve purpose of lowering blood glucose. Growth of granulation tissue in the insulin group was significantly different and increased at day seven from the control group indicating wound bed preparation occurred quicker in the insulin group. The CD34 detection and MVD counting initially showed no significant difference but at day five after injection a significant difference between the two groups indicating that local injection in diabetic foot ulcers could promote granulation tissue.

Conclusion: Insulin injection directly in the wound showed statistically significant increases in granulation tissue while also decreasing systemic glucose levels. The authors demonstrated that insulin injection in wounds is a way to manage systemic blood glucose levels and to decrease the wound bed preparation time. I believe that with further research in the dosing of the insulin for injections in wounds, this could be a feasible alternative to subcutaneous injections of insulin while also gaining benefits of the increased angiogenesis at the wound site, and therefore, faster wound healing. I would consider using this technique in stable patients living with diabetes once more dosage recommendations are established. 

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