An MMP/TIMP ratio scoring system as a potential predictive marker of diabetic foot ulcer healing

The mechanism of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in diabetic foot ulcers (DFUs) is unclear. The purpose of this study was to describe changes in MMP-1, MMP-9, and TIMP-1 levels during DFU healing, and to search for any correlation in the changes in MMP levels with wound healing, in order to find possible predictors of healing.

Patients with a DFU were recruited and placed into two groups, according to the degree of wound healing: 'good healers' and 'poor healers'. Levels of MMP-1, MMP-9, and TIMP-1 were analysed by ELISA (enzyme-linked immunosorbent assay).

A total of 22 patients participated in the study. The MMP-1 level was significantly higher at weeks zero (W0) and 12 (W12) in 'good healers' than in 'poor healers' (p=0.045 and 0.008, respectively). In contrast, the MMP-9 level was significantly lower in 'good healers' than in 'poor healers' at W0, W4, and W12 (p=0.001, 0.001 and 0.028, respectively). Receiver operator curve (ROC) analysis of the MMP-9 level, MMP-1/TIMP-1 ratio, and MMP-9/TIMP-1 ratio at W0 provided cut-off levels of 0.38, 0.056, and 9.06, respectively, which were best predictive of a reduction in wound area at W4 ('good healers' versus 'poor healers'; thereby predicting wound healing condition at W12) with a sensitivity of 81.8%, 81.8%, and 90.9%, and a specificity of 64.6%, 55%, and 64.6%, respectively.

A 'poor healing scoring system' is therefore proposed that could be determined on patient admission, which has the potential to be used clinically as a predictor of healing, thus allowing an appropriate treatment plan to be developed.