Abstract
Objectives Chronic foot ulceration is a severe complication of diabetes, driving morbidity and mortality. The aim of our study was to identify novel biomarkers of impaired wound healing in diabetic foot ulcers. Methods 109 patients with neuropathic diabetic foot ulcers and 30 burn victims otherwise healthy participated. Antibody-coated glass slide arrays were used to determine the levels of 80 human cytokines in pooled plasma or pooled wound exudate of diabetic foot ulcers with rapidly healing (RH, n = 12) and matched nonhealing (NH, n = 12) patients. Potential biomarkers were confirmed in an independent cohort by enzyme-linked immunosorbent assay (ELISA). Results Protein array profiling identified 27 proteins or 15 proteins significantly altered in protein profiling of pooled plasma or pooled wound exudate of 12 RH patients compared with 12 matched NH patients, respectively. In an independent cohort, quantitative ELISA validation confirmed a decrease in MCP-2 and ENA-78 levels in NH patients versus RH patients or burn victims. After adjusting for the traditional risk factors (sex, age, body mass index, fasting plasma glucose, ulcer area, HbA1C, diabetes duration, hyperlipidemia, and antibiotic therapy), only wound exudate level of ENA-78 remained having a significant association with an increased odds ratio (OR) for wound healing by binary logistic regression analysis (P < 0.05). Conclusion Decreased wound exudate ENA-78 was independently associated with wound healing of patients with diabetic foot. Exudate ENA-78 level is implicated as a novel predictor of wound healing in patients with diabetic foot ulcers.
Highlights
Diabetic foot is a severe chronic diabetic complication and has become a major public health problem that consists of neurological disorders and peripheral vascular diseases in the lower extremities [1, 2]
Even after adjusting for traditional confounding risk factors, exudate level of Epithelial neutrophil activator-78 (ENA-78) was found to be significantly decreased in the NH group compared with the rapidly healing (RH) group
Based on the patient characteristics, fasting plasma glucose (FPG) and HbA1C were found to be significantly increased in the NH group compared with the RH group in the validation cohort 1 group, which means that glycemic control plays an important role in wound healing
Summary
Diabetic foot is a severe chronic diabetic complication and has become a major public health problem that consists of neurological disorders and peripheral vascular diseases in the lower extremities [1, 2]. Wound healing is a complex process involving several tissues, cell types, and biological pathways; the risk factors consist of coagulation, formation, and regression of the granulation tissue, epithelial gap closure, angiogenesis, and inflammation, but the molecular mechanisms leading to impaired wound healing in diabetes are incompletely understood [5]. Because of the difficulty in obtaining tissue samples, the Journal of Diabetes Research studies on DFU are limited; plasma or wound exudate is much easier to be obtained in clinical practice. Early recognition of wound healing and more valuable biomarkers in plasma or exudate are urgently required as early predictor markers of wound healing for reducing the high number of amputations
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