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Outcome predictors for wound healing in patients with a diabetic foot ulcer.

ABSTRACT: The aim of this study was to identify diabetic foot ulcer (DFU) patients at risk for the development of a hard-to-heal wound. This is a post-hoc analysis of a prospective cohort study including a total of 208 patients with a DFU. The primary endpoints were time to healing and the development of a hard-to-heal-wound. Univariable and multivariable logistic and Cox regression analysis were used to study the associations of patient characteristics with the primary endpoints. The number of previous DFUs [odds ratio (OR): 1.42, 95% confidence interval (CI): 1.01-1.99, P = .04], University of Texas (UT) classification grade 2 (OR: 2.93, 95% CI: 1.27-6.72, P = .01), UT classification grade 3 (OR: 2.80, 95% CI: 1.17-6.71, P = .02), and a diagnosis of foot stand deformation (OR: 1.54, 95% CI: 0.77-3.08, P = .05) were significantly associated with the development of a hard-to-heal wound. Only UT classification grade 3 (HR: 0.61, 95% CI: 0.41-0.90, P = .01) was associated with time to healing. The number of previous DFUs, UT classification grade, and a diagnosis of foot deformation are significantly associated with development of a hard-to-heal wound in patients with a DFU. The only predictor significantly associated with time to healing was UT classification grade 3. These patient characteristics can be used to identify patients at risk for the development of hard-to-heal wounds, who might need an early intervention to prevent wound problems.

SUBMITTER: Mohammad Zadeh M

PROVIDER: S-EPMC7948747 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundSeveral epidemiological studies in diabetic patients have demonstrated a protective effect of metformin to the development of several types of cancer. The underlying mechanisms of such phenomenon is related to the effect of metformin on cell proliferation among which, mTOR, AMPK and other targets have been identified. However, little is known about the role that metformin treatment have on other cell types such as keratinocytes and whether exposure to metformin of these cells might have serious repercussions in wound healing delay and in the development of complications in diabetic patients with foot ulcers or in their exacerbation.Material and methodsHaCaT Cells were exposed to various concentrations of metformin and cell viability was evaluated by a Resazurin assay; Proliferation was also evaluated with a colony formation assay and with CFSE dilution assay by flow cytometry. Cell cycle was also evaluated by flow cytometry by PI staining. An animal model of wound healing was used to evaluate the effect of metformin in wound closure. Also, an analysis of patients receiving metformin treatment was performed to determine the effect of metformin treatment on the outcome and wound area. Statistical analysis was performed on SPSS v. 18 and GraphPad software v.5.ResultsMetformin treatment significantly reduces cell proliferation; colony formation and alterations of the cell cycle are observed also in the metformin treated cells, particularly in the S phase. There is a significant increase in the area of the wound of the metformin treated animals at different time points (P<0.05). There is also a significant increase in the size and wound area of the patients with diabetic foot ulcers at the time of hospitalization. A protective effect of metformin was observed for amputation, probably associated with the anti inflammatory effects reported of metformin.ConclusionsMetformin treatment reduces cell proliferation and reduces wound healing in an animal model and affects clinical outcomes in diabetic foot ulcer patients. Chronic use of this drug should be further investigated to provide evidence of their security in association with DFU.

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Outcome predictors for wound healing in patients with a diabetic foot ulcer.

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