Analyzing Available Data on Inflammatory Markers in Diabetic Foot Infection

A recent meta-analysis in Wounds took a deeper dive into the role of inflammatory markers in detecting diabetic foot infections.¹ The authors noted that, when considered piecemeal, the existing research was confusing, with questions being raised as to the reliability of these markers. To their knowledge, they stated that no meta-analysis existed that examined the relationship of these inflammatory markers in the context of patients with and without diabetic foot infections. In order to assemble the relevant research, they searched several online databases, assessing quality with the Newcastle-Ottawa Scale, and using a random-effects model to compare inflammatory marker trends between diabetic feet with and without infection. Specifically, the researchers looked at white blood cell (WBC) count, C-reactive protein (CRP), and procalcitonin (PCT).¹

The authors included 10 studies, encompassing 785 patients. Their meta-analysis revealed an increase in the mean levels of each of the above inflammatory markers in patients with diabetic foot infections.¹ The authors commented on the rationale for this finding. First, they noted that WBCs are a foundational marker for infection, making its elevation in diabetic foot infection not surprising. CRP elevation likely results from endothelial cells generating interleukin-6 (IL-6), which triggers the liver to create acute phase proteins such as CRP in the context of an infection. PCT increases in the setting of a diabetic foot infection result from a response to lipopolysaccharide, among other factors. Combined with the expected inflammatory response to common causative organisms in diabetic foot infection, the resultant increases in these markers have a biological explanation.

There are other characteristics of these markers, however, that the authors discussed in their study.¹ WBC count is a common laboratory test that helps to detect infection; however, it also can indicate nonspecific inflammation and provide information related to innate and acquired immunity. CRP is not just an inflammatory marker, but also relates to mediation of inflammation and innate immunity. The authors contended that further study of WBC count and CRP may lead to more insights on preventing diabetic foot infection, as more information emerges on their role in the immune response.¹

Both meta-analyses of WBC levels and CRP were deemed stable by the authors, but that of PCT was not. However, they went on to say that PCT could still play a role in detecting diabetic foot infections. Specifically, looking back at previous research cited in their study, its function may be in guiding antibiotic implementation.¹

As a whole, the authors found that these 3 inflammatory markers showed utility as indices for detecting diabetic foot infection, which could aid in early intervention and prevention measures, due to their relative convenience and speed of analysis.¹ The authors acknowledge that they did not delve into stratifying the severity of the infections in the participants, and that sample size, publication bias, and heterogeneity among the study groups were potential limitations.¹ They recommended further study to validate their findings.

Overall, the authors cited that, “These findings strengthen the evidence that diabetic foot infection is accompanied by abnormal levels of WBC, CRP, and PCT. These inflammatory markers can be effective laboratory indexes that play important roles in the detection of diabetic foot infection. Additionally, a thorough understanding of these mechanisms will help in the development of new strategies to prevent diabetic foot infection through monitoring WBC count, CRP level, and PCT level.”1

Reference

1. Wang YT, Zhang LX, Li Y, Zhao J, Chen HL. Inflammatory markers in diabetic foot infection: a meta-analysis. Wounds. 2023;35(12):425-432. doi:10.25270/wnds/082421.03