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An important multicenter study from our colleagues Sen and coworkers and the NIH’s Diabetic Foot Consortium, conducted through the NIDDK Diabetic Foot Consortium, has provided strong evidence that functional closure—not just structural closure—matters when it comes to diabetic foot ulcers (DFUs).

Published in Diabetes Care, this prospective noninterventional study followed 418 patients with recently healed DFUs. Using point-of-care devices to measure transepidermal water loss (TEWL) at the wound site, investigators assessed whether the barrier integrity of “closed” wounds predicted recurrence over 16 weeks.

👉 NIH Diabetic Foot Consortium link

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Key Findings

• Recurrence rate: 21.5% of patients experienced recurrence within 16 weeks of closure.
• Barrier function matters: DFUs with high TEWL (>30 g·m⁻²·h⁻¹) at closure were more than twice as likely to recur compared with those with low TEWL (odds ratio 2.66; 95% CI 1.57–4.49).
• Time to recurrence: Kaplan–Meier analysis showed that patients with high TEWL recurred significantly sooner than those with low TEWL.
• Clinical utility: TEWL may serve as a noninvasive, point-of-care biomarker to differentiate between structural closure and functional closure.

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Why This Matters

Traditional definitions of wound healing, including the FDA’s current criteria, focus on surface re-epithelialization. Yet, this study shows that even “healed” wounds may harbor defective barrier function. Elevated TEWL highlights incomplete restoration of the skin’s defense system, leaving patients vulnerable to early recurrence.

This work provides a scientific and clinical rationale to move beyond binary healed/not-healed definitions toward incorporating barrier integrity into wound closure endpoints. Importantly, it connects preclinical findings on biofilm, inflammation, and tight junction disruption with human clinical outcomes.

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Looking Forward

For clinicians and patients alike, this is a reminder that closure does not always equal cure. A wound that looks healed may still be fragile. Measuring TEWL in practice could:

• Help identify high-risk patients at the moment of closure.
• Inform preventive strategies such as enhanced offloading, infection surveillance, or adjunctive dressings.
• Support a broader shift toward “ulcer-free, hospital-free, activity-rich days” as meaningful outcomes.

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Citation:

Sen CK, Gordillo GM, Roy S, et al. 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. Diabetes Care. 2025;48(7):1-8. doi:10.2337/dc25-0300

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