Biochemical and Immunological Predictors of Non-healing in Individuals with Early-stage Diabetic Foot Ulcers

Objective: The goal of this study was to identify biochemical and immunological parameters from the blood as predictors of non-healing in early-stage diabetic foot ulcers. Research Design and Method: We performed a cross-sectional prospective cohort study among individuals with early-stage foot ulcers visiting the Karnataka Institute of Endocrinology Research over a 2.5-year period. Histopathological, biochemical, and immunological data (a total of 31 parameters) from 52 individuals were collected and analyzed to determine if predictors of non-healing may be identified. Data analysis was performed using traditional univariate analyses as well as univariate and multivariable logistic regression. Results: Individual histopathological and biochemical parameters did not show any differences between healed and non-healed individuals. However, conventional univariate analysis and univariate logistic regression analysis showed that the expression of the cell-surface proteins CD63, HLA-DR and CD11b on monocytes (CD14+) was significantly lower in non-healed individuals, but with moderate discriminative ability as assessed by area under the curve (AUC) of Receiver Operating Characteristics (ROC) curve. In comparison, a multivariable logistic regression model identified four of the 31 parameters to be salient predictors and demonstrated high discrimination ability with an AUC of ROC value of 0.87. Among the four identified parameters, LDL cholesterol (OR 18.83, CI 18.83-342) and cell-surface expression of CD63 on monocytes (OR 0.12, CI 0.12-0.45) were significant. Conclusion: Through this study we conclude that LDL cholesterol and cell-surface expression of CD63 on monocytes are strong positive and negative predictors of non-healing, respectively, in individuals with early-stage DFU. Following validation in a larger cohort, these parameters may be used by the clinician for early identification of non-healers.