Immune Mediators in Patients With Acute Diabetic Foot Syndrome

  1. Christian Weigelt, MD1,
  2. Bettina Rose, MD1,
  3. Ulrike Poschen, DIPL, OEC, TROPH1,
  4. Dan Ziegler, MD, FRCPE1,2,
  5. Gerd Friese, MD1,3,
  6. Kerstin Kempf, PHD1,4,
  7. Wolfgang Koenig, MD5,
  8. Stephan Martin, MD1,4 and
  9. Christian Herder, PHD, MSC1
  1. 1Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany;
  2. 2Department of Internal Medicine/Metabolic Diseases, Heinrich Heine University Düsseldorf, Düsseldorf, Germany;
  3. 3Medicenter Plettenberg, Plettenberg, Germany;
  4. 4Westdeutsches Diabetes- und Gesundheitszentrum, Sana Krankenhaus Gerresheim, Sana Kliniken Düsseldorf, Düsseldorf, Germany;
  5. 5Department of Internal Medicine II–Cardiology, University of Ulm Medical Center, Ulm, Germany.
  1. Corresponding author: Bettina Rose, bettina.rose{at}
  1. C.W. and B.R. contributed equally to this study.


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-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).

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.


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    • Received December 27, 2008.
    • Accepted April 29, 2009.
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  1. Diabetes Care vol. 32 no. 8 1491-1496
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