Immune Mediators in Patients With Acute Diabetic Foot Syndrome

Abstract

OBJECTIVESubclinical 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 METHODSCirculating 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.RESULTSPatients with an acute foot ulcer had higher levels of C-reactive protein (CRP), fibrinogen, interleukin (IL)-6, macrophage migration inhibitory factor, macrophage inflammatory protein-1α, and interferon-γ–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).CONCLUSIONSWe 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.

Clinical and surgical characteristics of infected diabetic foot ulcers in a tertiary hospital of Mexico

“…Although only 25 (56% of the 45 patients that reported smoking) suffered an amputation, a history of smoking is important in the development of diabetic foot ulcers because of the endothelial damage it produces. In particular, it has been reported that smokers suffer more from diabetic foot ulcers and have a higher risk of amputations than non-smokers [29,35,37,47,48]. …”

Wound Fluid Diagnostics in Diabetic Foot Ulcers

“…The analysis of a complete set of mediators can therefore be considered to be of more value than the single analysis of only one single analyte (Gardy et al 2009;de Jager et al 2003). Although protein microarray technology has been successfully applied for the analysis of multiple analytes in complex biological mixtures -such as plasma, serum, urine and cerebrospinal fluid-publications using protein arrays for the analysis of wound status are rare (Hsu et al 2008;Weigelt et al 2009;Craig-Schapiro et al 2011;Swain et al 2011). For instance, Grimstad et al measured the concentration of 27 different cytokines in wound fluid derived from acute wounds using a bead-based system (Grimstad et al 2011).…”

“…Consecutively, a variety of immune mediators -including acute phase proteins, cytokines and chemokines-were examined in the plasma of patients with diabetic foot syndrome. These markers included CRP and fibrinogen as well as IL-6, IL-8, IL-18, macrophage inflammatory protein 1 (MIP1), interferon -inducible protein-10 (IP10), macrophage migration inhibitory factor (MIF), macrophage chemoattractant protein 1 (MCP1) and RANTES (Weigelt et al 2009). Both of the studies just cited were able to connect the occurrence of certain systemic inflammatory markers with the presence of infection in the diabetic foot.…”

Diabetic foot syndrome: Immune-inflammatory features as possible cardiovascular markers in diabetes

“…Weigelt et al [34] analyzed the possible relationship between foot ulcers and immune status in diabetic subjects with and without foot ulcers by evaluating some immune mediators. Authors reported how circulating levels of some inflammatory markers such as acute-phase proteins, cytokines, and chemokines were higher in patients with diabetic foot.…”