Letter to the editor: Vitamin D levels and diabetic foot ulcers: Is there an association?

Dear editor,

I read with great interest the study entitled “Association between vitamin D deficiency and diabetic foot ulcer wound in diabetic subjects: A meta‐analysis” by Lin J et al (1). This meta‐analysis revealed a high prevalence rate of low vitamin D levels in diabetic patients with foot ulcers compared with the control group (diabetic patients without foot ulcers) (1). However, I have the following comments related to the validity of this review:

1. The author concludes that diabetic patients with foot ulcers had low vitamin D levels. I think this should be cautiously interpreted in view of the marked heterogeneity between the included studies in this meta‐analysis. As the majority of recruited studies are of cross‐sectional design, the causal relationship between vitamin D levels and diabetic foot ulcers cannot be inferred. In fact, the diabetic foot ulcer might be the cause of low vitamin D levels in these studies. Also, potential confounders other than age, gender, and ethnicity, such as the effect of seasonal timing, glycaemic control, duration of diabetes, obesity, and the presence of other comorbidities on vitamin D levels, were not well addressed in this meta‐analysis and might affect the overall incidence of low vitamin D levels. For instance, Tang W et al, found a remarkable impact of seasonal fluctuations, with lower levels of vitamin D observed in winter and spring compared with summer and autumn (2). Also, diabetic patients with poor glycaemic control tend to have lower vitamin D levels (2, 3). In addition, the potential of initiating or adjusting vitamin D supplementation after testing was not accounted for and consequently may have affected the findings of this meta‐analysis. The author might have considered conducting a sub‐analysis to mitigate the impact of potential confounding variables on vitamin D levels. Also, using an adjusted Odds ratio instead of a crude Odds ratio is more accurate in estimating the association between vitamin D levels and diabetic foot ulcers.

2. In the statistical section, the author linked the use of a random versus fixed effects model to heterogeneity level. While the use of a random effects model sounds reasonable in this analysis, its choice should not be based on the heterogeneity level (4). In fact, the power of heterogeneity testing is suboptimal, and a non‐significant level of heterogeneity does not eliminate the presence of true heterogeneity between studies (4). The use of a random effects model is more appropriate when it is more likely to fit the actual sampling distribution and when the findings of the meta‐analysis are generalizable to a wider population (4).

3. While a randomised controlled double‐blinded trial by Razzaghi R et al, showed a significant association between vitamin D supplements and reduction in ulcer length, width, depth, and erythema rate, it was proposed that these effects were indirect and driven mainly by the positive effect of vitamin D supplements on other parameters that contribute to wound healing, such as improved glycaemic homeostasis (5).

Considering the above factors and despite the relatively high prevalence rate of vitamin D deficiency in diabetic patients with foot ulcers, such an association needs to be cautiously interpreted.