# Diabetic Foot Ulcer Wound Fluid Biomarker

> **NIH NIH R61** · INDIANA UNIVERSITY INDIANAPOLIS · 2022 · $485,875

## Abstract

The 2020 CDC national diabetes statistics report identified that 34.2 million Americans, or 10.5% of the
population had diabetes in 2018. It is estimated that over the course of their lifetime up to a third of these people
with diabetes will develop a diabetic foot ulcer (DFU). The five-year mortality and direct costs of care for people
with diabetic foot complications are comparable to cancer. Approximately 40-60% of nontraumatic lower limb
amputations worldwide are caused by diabetic complications, and 80% of these amputations follow DFU. In
patients with hard-to-heal DFUs, treatment with multiple therapies is often necessary to manage stubborn
wounds. The current DFU treatment algorithm uses failure to improve (>50% wound area reduction) after four
weeks of standard of care (SoC) therapy to make a clinical decision on changing the therapy. The lack of
objective early indicators of wound healing outcomes handicaps DFU care strategy. Biomarkers that predict non-
healing (i.e., refractory to SoC) would provide an objective basis for rationally adopting alternate treatment
regimen to wound care providers in a timely manner. This proposal rests on our premise that non-healing diabetic
wounds would suffer from metabolic impairments which in turn would be reflected by changes in metabolites
contained in wound fluids (WF). A metabolomics approach was used to screen 578 metabolites from 161 WF
from chronic wound patients. Of all these metabolites, ONE PARAMETER emerged as a robust predictor of non-
healing: low Cysteine (Cys)/Cystine (CysS). A prospective preliminary study on DFU patients (N=24) showed
that low Cys/CysS in WF predicts non-healing. A point-of-care microtiter-plate (standard hospital assay platform)
based test was used. Because the proposed work seeks to establish Cysteine Redox as a biomarker of non-
healing or Open wound, the study is named CREDO. The R61 preparatory phase is named 2CREDO (towards
CREDO), and the R33 phase is referred to as CREDO. Aim 1: Validate the use DFU wound fluid low Cys/CysS
ratio (<3.43 cut-off) as a primary biomarker to predict non-healing of DFU. Aim 2: Develop a complete clinical
protocol to validate the use of Cys/CysS ratio in wound fluids to predict the healing of adult DFU. Aim 3: Conduct
a multi-center clinical study of diabetic foot ulcer patients to perform detailed validation of wound fluid based
Cys/CysS ratio as a biomarker to predict diabetic foot ulcer healing. Aim 4: Initiate discussions with FDA to
establish Cys/CysS as a clinical biomarker to predict DFU healing. The proposed work will be conducted as
ancillary Study of the current NIDDK Diabetic Foot Consortium (DFC) who have approved feasibility of our
protocol.

## Key facts

- **NIH application ID:** 10396775
- **Project number:** 1R61DK131909-01
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Sashwati Roy
- **Activity code:** R61 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $485,875
- **Award type:** 1
- **Project period:** 2022-04-25 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10396775

## Citation

> US National Institutes of Health, RePORTER application 10396775, Diabetic Foot Ulcer Wound Fluid Biomarker (1R61DK131909-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10396775. Licensed CC0.

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