Cholesterol Levels and Monocyte Phenotype Are Predictors of Nonhealing in Individuals with Low-Grade Diabetic Foot Ulcers: A Prospective Cohort Study

Objective: Inflammation has been linked to progression of diabetic foot ulcers (DFU); however, specific predictive markers of nonhealing are scarce. The goal of this study was to identify biochemical and immunological parameters from the blood as predictors of nonhealing in grade 1 and grade 2 DFU.Approach: Individuals with low-grade foot ulcers were enrolled in the study to determine if histopathological, biochemical, and immunological parameters could be used to predict individuals whose ulcers would not heal. Data analysis was performed using traditional univariate analyses as well as univariate and multivariable logistic regression, and STROBE guidelines were used for reporting data.Results: Among the 52 individuals who completed the study, we observe that no single histopathological and biochemical parameter was predictive. Conventional univariate analysis and univariate logistic regression analysis showed that the expression of the cell surface proteins CD63, HLA-DR, and CD11b on monocytes was significantly lower in nonhealed individuals, but with moderate discriminative ability. In comparison, a multivariable logistic regression model identified four of the 31 parameters to be salient predictors with low density lipoprotein (LDL) cholesterol (odds ratio [OR] 18.83, confidence interval [CI] 18.83-342) and cell-surface expression of CD63 on monocytes (OR 0.12, CI 0.12-0.45) showing significance and demonstrating high discrimination ability.Innovation: The approach of using a combination of biochemical and immunological parameters to predict ulcer healing is new.Conclusion: Through this study we conclude that LDL cholesterol and cell-surface expression of CD63 on monocytes strongly correlate with nonhealing in individuals with grade 1 and grade 2 DFU.