Abstract

Objective— Subclinical inflammation is an important risk factor of type 2 diabetes and diabetic complications. However, data on the association between inflammation and acute diabetic foot syndrome are very scarce. The aim of this study was to compare systemic immune mediators in diabetic patients with and without ulcer and to identify modulating factors.

Research design and methods— Circulating levels of acute-phase proteins, cytokines and chemokines were measured in diabetic patients with ulcer (n=170) and without ulcer (n=140). Eighty-eight per cent of patients had type 2 diabetes.

Results— Patients with acute foot ulcer had higher levels of C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), macrophage migration inhibitory factor (MIF), macrophage inflammatory protein-1α (MIP-1α) and interferon-γ-inducible protein-10 (IP-10) as well as lower levels of RANTES (regulated on activation, normal T-cell expressed and secreted) (all P<0.01). No differences were found for IL-8, IL-18 and monocyte chemoattractant protein-1 (MCP-1). Most of these associations persisted after adjusting for demographic, anthropometric, metabolic confounders and diabetic complications. In multivariate models, size of ulcer according to the University of Texas classification, but not the grade of infection, was independently associated with three markers of subclinical inflammation (CRP, IL-6 and fibrinogen).

Conclusions— We demonstrate in our cross-sectional study that acute foot ulcers and their severity are associated with a marked up-regulation of acute-phase proteins, cytokines and chemokines independently of the concomitant infection. Further studies should investigate whether an activation of the immune system precedes the development of foot ulcer and whether anti-inflammatory therapies might be effective.