OBJECTIVE Subclinical
inflammation is an important risk factor for
type 2 diabetes and
diabetes complications. However, data on the association between
inflammation and acute
diabetic foot syndrome are scarce. The aim of this study was to compare systemic immune mediators in diabetic patients with and without an
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 an
ulcer (n = 170) and without an
ulcer (n = 140). Of the patients, 88% had
type 2 diabetes. RESULTS Patients with an acute
foot ulcer had higher levels of
C-reactive protein (CRP),
fibrinogen,
interleukin (IL)-6,
macrophage migration inhibitory factor, macrophage inflammatory protein-1alpha, and
interferon-gamma-inducible protein-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. Most of these associations persisted after adjustment for demographic and anthropometric data, metabolic confounders, and
diabetes 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 upregulation 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.