Increased ratio of serum matrix metalloproteinase-9 against TIMP-1 predicts poor wound healing in diabetic foot ulcers

Abstract

Objective: Little is known about serum concentrations of Matrix Metalloproteinase-9 (MMP-9), MMP-2, TIMP-1 and TIMP-2 in diabetic patients with foot ulcers. This study demonstrates their relationship with wound healing.

Methods: Ninety-four patients with diabetic foot ulcers were recruited in the study. Serum MMP-9, MMP-2, TIMP-1 and TIMP-2 were measured at the first clinic visit and the end of 4-week treatment and followed up till 12 weeks. According to the decreasing rate of ulcer healing area at the fourth week, we divided those cases into good and poor healers. Through analyses, we explore the possible relationship among those factors and degree of wound healing.

Results: The median level of serum MMP-9 in good healers was lower than poor healers at first visit (124.2 μg/L vs 374.6 μg/L, p<0.05), and after 4-week therapy it decreased 5-fold approximately. In contrast, the change in MMP-9 concentration did not reach statistical significance in poor healers. MMP-2, TIMP-1 and TIMP-2 varied slightly in both good healers and poor healers. The MMP-9/TIMP-1 ratio better reflected the healing than MMP-9 alone before therapy and after 4 week treatment (r = -0.6475 vs -0.3251, r = -0.7096 vs -0.1231, respectively). Receiver Operator Curve (ROC) showed that the cutoff for MMP-9/TIMP-1 ratio at <0.395 best predicted a reduction in wound area of 82% at the end of 4-week treatment with a sensitivity of 63.6% and a specificity of 58.6% (area under the curve 0.658, p < 0.001).

Conclusions: Detecting serum MMP-9/TIMP-1 ratio on admission might be a predictor of healing and might provide a novel target for the future therapy in diabetic foot ulcers.