Non-classical monocytes frequency and serum vitamin D3 levels are linked to diabetic foot ulcer associated with peripheral artery disease

J Diabetes Investig. 2023 Oct;14(10):1192-1201. doi: 10.1111/jdi.14048. Epub 2023 Jul 2.

Abstract

Aims/introduction: Peripheral artery disease (PAD) serves as a risk factor for diabetic foot ulcers (DFUs). PAD pathology involves atherosclerosis and impaired immunity. Non-classical monocytes are believed to have an anti-inflammatory role. 1,25-Dihydroxy vitamin D (vitamin D3 ) is claimed to have immune-modulating and lipid-regulating roles. Vitamin D receptor is expressed on monocytes. We aimed to investigate if circulating non-classical monocytes and vitamin D3 were implicated in DFUs associated with PAD.

Materials and methods: There were two groups of DFU patients: group 1 (n = 40) included patients with first-degree DFUs not associated with PAD, and group 2 (n = 50) included patients with DFU with PAD. The monocyte phenotypes were detected using flow cytometry. Vitamin D3 was assessed by enzyme-linked immunosorbent assay.

Results: DFU patients with PAD showed a significant reduction in the frequency of non-classical monocytes and vitamin D3 levels, when compared with DFU patients without PAD. The percentage of non-classical monocytes positively correlated with vitamin D3 level (r = 0.4, P < 0.01) and high-density lipoprotein (r = 0.5, P < 0.001), whereas it was negatively correlated with cholesterol (r = -0.5, P < 0.001). Vitamin D3 was negatively correlated with triglyceride/high-density lipoprotein (r = -0.4, P < 0.01). Regression analysis showed that a high vitamin D3 serum level was a protective factor against PAD occurrence.

Conclusions: Non-classical monocytes frequency and vitamin D3 levels were significantly reduced in DFU patients with PAD. Non-classical monocytes frequency was associated with vitamin D3 in DFUs patients, and both parameters were linked to lipid profile. Vitamin D3 upregulation was a risk-reducing factor for PAD occurrence.

Keywords: Diabetic foot ulcer; Monocyte subsets; Vitamin D3.

MeSH terms

  • Cholecalciferol
  • Diabetes Mellitus*
  • Diabetic Foot* / etiology
  • Humans
  • Lipoproteins, HDL
  • Monocytes / pathology
  • Peripheral Arterial Disease* / complications

Substances

  • Cholecalciferol
  • Lipoproteins, HDL