Role of lowered level of serum vitamin D on diabetic foot ulcer and its possible pathomechanism: A systematic review, meta-analysis, and meta-regression

Aim

To investigate the association between serum vitamin D (SVD) level and DFU development and to emphasize the involved pathomechanism.

Methods

The search was performed on 12 databases for literature published until 10 March 2023. The protocol has been registered on PROSPERO (CRD42023415744). The selection for the included records followed PRISMA framework. Meta-analyses using random effects model were performed and the data were presented as SMD and 95% CI. Meta-regression was performed to identify factors contributing to the heterogeneity in the pooled analysis.

Results

Twenty-one studies were included in the systematic review with a total number of patients reaching 9,570. Of which, as many as 18 studies were eligible for the meta-analysis. The SDV level is significantly lower in DFU group (p-total=0.0037; SMD= -1.2758; [95% CI: -2.0786 to -0.4730]). Based on the meta-regression, age, study location (based on the continent), and total cholesterol level contribute to the high heterogeneity (p<0.01). In the pooled analysis, inflammatory markers such as serum levels of CRP (n = 4), ESR (n = 3), IL-6 (n = 3), and IL-8 (n = 2) are found significantly higher in DFU group at p<0.01.

Conclusion

Lowered SVD level is associated with DFU, where the pathomechanism for this relationship might involve inflammation and infection susceptibility.