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Multicenter Study
. 2025 Jul 1;48(7):1233-1240.
doi: 10.2337/dc25-0300.

High Transepidermal Water Loss at the Site of Wound Closure Is Associated With Increased Recurrence of Diabetic Foot Ulcers: The NIDDK Diabetic Foot Consortium TEWL Study

Affiliations
Multicenter Study

High Transepidermal Water Loss at the Site of Wound Closure Is Associated With Increased Recurrence of Diabetic Foot Ulcers: The NIDDK Diabetic Foot Consortium TEWL Study

Chandan K Sen et al. Diabetes Care. .

Abstract

Objective: The National Institute of Diabetes and Digestive and Kidney Diseases Diabetic Foot Consortium tested the hypothesis that compromised restoration of the skin barrier function of closed diabetic foot ulcers (DFUs), as measured by high transepidermal water loss (TEWL), is associated with an increased risk of DFU recurrence.

Research design and methods: This was a multicenter noninterventional study measuring TEWL in 418 adult participants with diabetes and a recently healed DFU. TEWL was measured at the center of the closed wound and at an anatomically similar reference area on the contralateral foot within 2 weeks of wound closure (visit 1); measurements were repeated at a wound closure confirmation visit 2 weeks later (visit 2). Participants were observed for up to 16 weeks to assess for wound recurrence. Participant self-reported and clinician assessments of DFU wound recurrence were recorded.

Results: DFU recurrence by week 16 occurred in 21.5% of participants. Mean TEWL at the center of the healed DFU at visit 1 was higher for those with recurrence compared with those without (P = 0.006). Among participants with high TEWL (>30.05 g · m-2 · h-1), 35% reported wound recurrence by 16 weeks versus 17% of those with low TEWL. The odds ratio for recurrence for participants with high TEWL was 2.66 (P < 0.001). Self-reported wound recurrence was highly concordant with clinician assessment of wound recurrence.

Conclusions: Compromised wound healing mechanisms culminating in wound closure associated with defective skin barrier function is associated with increased risk of DFU recurrence. Measurement of TEWL has value as a predictor of functional wound healing and could affect clinical practice, leading to better outcomes.

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Conflict of interest statement

Duality of Interest. No potential conflicts of interest relevant to this article were reported.

Figures

None
Graphical abstract
Figure 1
Figure 1
TEWL measurement and association with recurrence. A: Side-by-side boxplots present TEWL differences between those with and without wound recurrence by 16 weeks postclosure in the pooled sample. B: ROC analysis from the simple logistic regression model for DFU wound recurrence by 16 weeks postclosure as a function of visit 1 TEWL in the pooled sample. C: Percentages of low (TEWL <30.05) and high (TEWL ≥30.05) values for visit 1 TEWL are summarized with a bar diagram for those with and without wound recurrence by 16 weeks postclosure in the pooled sample. ***P = 0.0003.
Figure 2
Figure 2
Time to wound recurrence within 16 weeks by high or low TEWL. A: Kaplan-Meier curve for time to wound recurrence by 16 weeks postclosure in the pooled sample by low (TEWL <30.05) and high (TEWL ≥30.05) visit 1 TEWL values. The x-axis marks the time to wound recurrence in days. The cumulative probability of surviving (i.e., no wound recurrence by 16 weeks post-closure) a given time is shown on the y-axis.

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