# Nonlinear Association Between Serum 25‐Hydroxyvitamin D and Cardiac Autonomic Dysfunction in Diabetic Foot: A Threshold Effect on Heart Rate Variability

**Authors:** Mingxin Bai, Donge Yan, Ruixue Feng, Xingwu Ran, Dawei Chen, Chun Wang, Lihong Chen, Shuang Lin, Sen He, Yan Liu, Murong Wu, Zhiyi Lei, Yun Gao

PMC · DOI: 10.1111/1753-0407.70109 · Journal of Diabetes · 2025-06-10

## TL;DR

Low vitamin D levels are linked to worse heart function in people with diabetic foot, especially when levels drop below 50 nmol/L.

## Contribution

This study identifies a threshold effect of vitamin D on heart rate variability in diabetic foot patients.

## Key findings

- Vitamin D levels below 50 nmol/L significantly increase the risk of cardiac autonomic dysfunction in diabetic foot patients.
- Positive associations exist between vitamin D levels and heart rate variability indices in diabetic foot individuals.
- The relationship between vitamin D and heart rate variability is nonlinear, with a notable threshold at 50 nmol/L.

## Abstract

Previous studies have shown that vitamin D deficiency was associated with both cardiac autonomic dysfunction and the development of diabetic foot (DF). However, the impact of vitamin D levels on heart rate variability (HRV) in individuals with DF, a high‐risk group, remains unclear. We explored the association between vitamin D status and HRV in individuals with DF.

A total of 458 individuals with DF were assessed for vitamin D levels by 25‐hydroxyvitamin D (25(OH)D) and evaluated for cardiovascular autonomic function using both time and frequency domains of the HRV measures. Multivariate regression analysis and restricted cubic spline regression were employed to examine the associations.

Vitamin D levels were positively associated with HRV indices in people with DF, including standard deviation of the normal sinus interval (SDNN), standard deviation of the 5‐min average RR intervals (SDANN), low‐frequency power (LF), high‐frequency power (HF), and the LF/HF ratio (all p < 0.05). The associations between serum 25(OH)D and cardiac autonomic dysfunction were nonlinear. When 25(OH)D levels were < 50 nmol/L, the odds ratio (OR) for predicted cardiac autonomic dysfunction per SD increase in 25(OH)D was 0.56 (95% CI, 0.44–0.72). However, no significant effect was observed when 25(OH)D levels exceeded 50 nmol/L.

This study demonstrates that lower 25(OH)D levels are associated with reduced HRV in individuals with DF. Specifically, when 25(OH)D levels fall below 50 nmol/L, the risk of cardiac autonomic dysfunction in people with DF significantly increases.

Lower 25(OH)D levels are associated with reduced HRV in individuals with DF. Specifically, when 25(OH)D levels fall below 50 nmol/L, the risk of cardiac autonomic dysfunction in people with DF significantly increases.

## Full-text entities

- **Diseases:** Cardiac Autonomic Dysfunction (MESH:D006331), DF (MESH:D017719)
- **Chemicals:** 25(OH)D (-), Vitamin D (MESH:D014807), 25-Hydroxyvitamin D (MESH:C104450)

## Full text

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## Figures

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## References

44 references — full list in the complete paper: https://tomesphere.com/paper/PMC12150134/full.md

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Source: https://tomesphere.com/paper/PMC12150134