# The relationship between at-risk foot and all-cause and cardiovascular mortality among the population with diabetes

**Authors:** Zhe Wu, Jin Dong, Meng Li, Chu Chu, Bin Wang

PMC · DOI: 10.3389/fmed.2025.1584949 · Frontiers in Medicine · 2025-07-21

## TL;DR

People with diabetes who have at-risk foot conditions face higher risks of death from all causes and cardiovascular issues, highlighting the need for early intervention.

## Contribution

This study identifies a significant association between at-risk foot and increased mortality in the general U.S. diabetic population.

## Key findings

- At-risk foot is linked to a 2.05-fold increase in all-cause mortality.
- Cardiovascular mortality is 2.49-fold higher in those with at-risk foot.
- Ischemic at-risk foot is associated with higher mortality than non-ischemic neuropathic at-risk foot.

## Abstract

Diabetic foot (DF) is a common complication among people with diabetes, typically caused by peripheral neuropathy (PN) and/or peripheral arterial disease (PAD) of the lower limbs. The existing research mainly focuses on cases of diabetic foot ulcers, while the relationship between at-risk foot and all-cause and cardiovascular mortality in the general U.S. population remains unclear.

This study utilized data from National Health and Nutrition Examination Survey (NHANES) 1999–2004 to conduct a cohort study. At-risk foot are defined as those in diabetic people who have concurrent PAD and/or PN, and without the presence of chronic ulcers in the lower extremities. Kaplan–Meier survival analysis and Multivariable Cox regression models were used to analyze the association between at-risk foot and all-cause and cardiovascular mortality, with subgroup analyses conducted.

A total of 946 participants were included in the study, of which 301 had at-risk foot. The median follow-up time was 190 months. Multivariable Cox regression analysis showed that the all-cause mortality (HR: 2.050, 95% CI: 1.524, 2.758) and cardiovascular mortality (HR: 2.494, 95% CI: 1.809, 3.438) in at-risk foot people were significantly higher than in those without at-risk foot. Additionally, people with ischemic at-risk foot had a higher risk of mortality compared to those with non-ischemic neuropathic at-risk foot.

Patients with at-risk foot in the diabetic population are significantly associated with increased all-cause and cardiovascular mortality. Early diagnosis and intervention of PAD and PN in diabetes people are crucial for reducing mortality risk.

## Linked entities

- **Diseases:** diabetes (MONDO:0005015), peripheral neuropathy (MONDO:0003620), peripheral arterial disease (MONDO:0005386)

## Full-text entities

- **Genes:** SLC17A5 (solute carrier family 17 member 5) [NCBI Gene 26503] {aka AST, ISSD, NSD, SD, SIALIN, SIASD}, GPT (glutamic--pyruvic transaminase) [NCBI Gene 2875] {aka AAT1, ALT, ALT1, GPT1, SGPT}
- **Diseases:** ischemia (MESH:D007511), CKD (MESH:D051436), foot ulcers (MESH:D016523), hypoglycemic (MESH:C000721848), limb diseases (MESH:D004421), vascular disease (MESH:D014652), Diabetes (MESH:D003920), DF (MESH:D017719), ischemic (MESH:D002545), Hypertension (MESH:D006973), PAD (MESH:D058729), chronic ulcers (MESH:D014456), gangrene (MESH:D005734), foot complications (MESH:D005534), cancers (MESH:D009369), PN (MESH:D010523), neuropathic (MESH:D009437), CVD (MESH:D002318), arterial occlusion (MESH:D001157), pain (MESH:D010146), death (MESH:D003643), motor dysfunction (MESH:D000068079), sensory abnormalities (MESH:D012678)
- **Chemicals:** cholesterol (MESH:D002784), blood glucose (MESH:D001786)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12319037/full.md

## References

34 references — full list in the complete paper: https://tomesphere.com/paper/PMC12319037/full.md

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Source: https://tomesphere.com/paper/PMC12319037