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. 2025 Sep 23;17(1):369.
doi: 10.1186/s13098-025-01962-8.

Association of high-density lipoprotein-related inflammatory indicators with diabetic foot ulcer in patients with diabetes: a population-based study

Renhe Deng  1 , Ruyi Tao  1 , Huiyi Luo  1 , Yueqi Gu  2 , Mengyu Yang  2 , Chaoqi Yin  3
Affiliations

Association of high-density lipoprotein-related inflammatory indicators with diabetic foot ulcer in patients with diabetes: a population-based study

Renhe Deng et al. Diabetol Metab Syndr. .

Abstract

Background: Early identification and treatment of diabetic foot ulcer (DFU) in diabetes mellitus (DM) patients is of great importance for improving life quality. This study aimed to investigate the association between high-density lipoprotein (HDL)-related inflammatory indicators, such as neutrophils-to-HDL ratio (NHR), monocyte-to-HDL ratio (MHR), lymphocyte-to-HDL ratio (LHR), platelet-to-HDL ratio (PHR), and the occurrence of DFU in DM patients.

Methods: This study included 1211 DM patients from the National Health and Nutrition Examination Survey (1999-2004). The relationship between HDL-related inflammatory indicators and DFU was explored with logistic regression models. Using a threshold effects analysis model, the association and inflection points between HDL-related inflammatory indicators and diabetic foot ulcer were investigated. Subgroup analyses were performed to further confirm the relationship in different populations. Mediation analysis was conducted to examine how red blood cell mediates the relationship between HDL-related inflammatory indicators and DFU.

Results: After multivariable adjustment, there is a strongly positive relationship between NHR, MHR, PHR, and DFU, whereas no such associations were found between LHR and DFU. Threshold effect analysis showed an inflection point of 0.29 between MHR and DFU, with a 4.51-fold increase in the prevalence of DFU for each unit rise in MHR when MHR was more than the inflection point. Mediation analysis revealed that red blood cell partially mediates the association between NHR and DFU.

Conclusions: These findings reveal a clear association between NHR, MHR, PHR, and an increased prevalence of DFU, which can be used as potential biomarkers in the prevention and management of DFU.

Keywords: Blood platelets; Diabetic foot; Lipoproteins, HDL; Lymphocytes; Monocytes; Neutrophils.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: All participants were required to provide informed consent before participation in the survey. Approval from the ethics board was not required as the data was public. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Flowchart of the selection process for study participants from the National Health and Nutrition Examination Survey (NHANES)
Fig. 2
Fig. 2
Adjusted smooth spline of non-linear relationship between high-density lipoprotein-related inflammatory indicators and diabetic foot ulcers. (A) NHR and DFU. (B) MHR and DFU. (C) PHR and DFU. The red solid line indicates the smooth curve fit, while the blue band depicts the 95% confidence interval. The model accounted for gender, age, race, marital status, and PIR. NHR, neutrophils-to-HDL ratio; MHR, monocyte-to-HDL ratio; PHR, platelet-to-HDL ratio; DFU, diabetic foot ulcer
Fig. 3
Fig. 3
The mediation role of red blood cells in the association between high-density lipoprotein-related inflammatory indicators and DFU. (A) NHR (B) MHR (C) PHR. Adjusted for gender, age, race/ethnicity. NHR, neutrophils-to-HDL ratio; MHR, monocyte-to-HDL ratio; PHR, platelet-to-HDL ratio; DFU, diabetic foot ulcer
See this image and copyright information in PMC

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