Wound Closure and Metabolic Parameter Variability in a db/db Mouse Model for Diabetic Ulcers

Abstract

Diabetic foot ulcers are a major cause of nontraumatic lower extremity amputations. Wound-healing researchers commonly use db/db mice as a model for diabetes, while the excisional wound correlates well with chronic foot ulcers. Recent clinical trials identified a correlation between glycemic control and cardiovascular complications in diabetic patients. The purpose of this study was to determine if the severity of diabetes was related to poor wound healing and the broad wound closure variability observed in diabetic db/db mice. Adult female C57BLKS/J, db+/-, and db/db mice were anesthetized followed by creation of a 1.5 x 1.5 cm full-thickness excisional wound. Wound closure was measured on postoperative days (PODs) 1, 5, 7, 10, 14, and 21. Weight, fasting blood glucose, and fasting insulin were also measured during the study. By POD 21 both wild-type and db+/- mice demonstrated complete wound closure. In db/db mice open wounds were still present at POD 21. There was a broad range of percent wound closure from 24 to 81% with a mean of 55%. Despite strong correlations between diabetic parameters, there was no significant correlation between wound closure rate and severity of diabetes. Diabetic db/db mice exhibit a significant impairment of healing in the excisional wound model. The variability of wound closure for individual mice did not correlate with severity of obesity, hyperglycemia, hyperinsulinemia, or insulin resistance. An extensive evaluation of basic diabetes parameters does not provide significant insight into the wound-healing process in the db/db mouse model.