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Immune mediators in patients with acute diabetic foot syndrome.

ABSTRACT: 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.

SUBMITTER: Weigelt C

PROVIDER: S-EPMC2713614 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature

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Immune mediators in patients with acute diabetic foot syndrome.

Weigelt Christian C Rose Bettina B Poschen Ulrike U Ziegler Dan D Friese Gerd G Kempf Kerstin K Koenig Wolfgang W Martin Stephan S Herder Christian C

Diabetes care 20090609 8

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 ulc ...[more]

PMID: 19509015

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Project description:Diabetic foot ulcerations have been extensively reported as vascular complications of diabetes mellitus associated with a high degree of morbidity and mortality. Diabetic foot syndrome (DFS), as defined by the World Health Organization, is an "ulceration of the foot (distally from the ankle and including the ankle) associated with neuropathy and different grades of ischemia and infection". Pathogenic events able to cause diabetic foot ulcers are multifactorial. Among the commonest causes of this pathogenic pathway it's possible to consider peripheral neuropathy, foot deformity, abnormal foot pressures, abnormal joint mobility, trauma, peripheral artery disease. Several studies reported how diabetic patients show a higher mortality rate compared to patients without diabetes and in particular these studies under filled how cardiovascular mortality and morbidity is 2-4 times higher among patients affected by type 2 diabetes mellitus. This higher degree of cardiovascular morbidity has been explained as due to the observed higher prevalence of major cardiovascular risk factor, of asymptomatic findings of cardiovascular diseases, and of prevalence and incidence of cardiovascular and cerebrovascular events in diabetic patients with foot complications. In diabetes a fundamental pathogenic pathway of most of vascular complications has been reported as linked to a complex interplay of inflammatory, metabolic and procoagulant variables. These pathogenetic aspects have a direct interplay with an insulin resistance, subsequent obesity, diabetes, hypertension, prothrombotic state and blood lipid disorder. Involvement of inflammatory markers such as IL-6 plasma levels and resistin in diabetic subjects as reported by Tuttolomondo et al confirmed the pathogenetic issue of the a "adipo-vascular" axis that may contribute to cardiovascular risk in patients with type 2 diabetes. This "adipo-vascular axis" in patients with type 2 diabetes has been reported as characterized by lower plasma levels of adiponectin and higher plasma levels of interleukin-6 thus linking foot ulcers pathogenesis to microvascular and inflammatory events. The purpose of this review is to highlight the immune inflammatory features of DFS and its possible role as a marker of cardiovascular risk in diabetes patients and to focus the management of major complications related to diabetes such as infections and peripheral arteriopathy.

Project description:BackgroundThe prevalence of diabetes mellitus has reached epidemic proportions, this condition may result in multiple and chronic invalidating long term complications. Among these, the diabetic foot, is determined by the simultaneous presence of both peripheral neuropathy and vasculopathy that alter the biomechanics of the foot with the formation of callosity and ulcerations. To diagnose and treat the diabetic foot is crucial to understand the foot complex kinematics. Most of gait analysis protocols represent the entire foot as a rigid body connected to the shank. Nevertheless the existing multisegment models cannot completely decipher the impairments associated with the diabetic foot.MethodsA four segment foot and ankle model for assessing the kinematics of the diabetic foot was developed. Ten normal subjects and 10 diabetics gait patterns were collected and major sources of variability were tested. Repeatability analysis was performed both on a normal and on a diabetic subject. Direct skin marker placement was chosen in correspondence of 13 anatomical landmarks and an optoelectronic system was used to collect the data.ResultsJoint rotation normative bands (mean plus/minus one standard deviation) were generated using the data of the control group. Three representative strides per subject were selected. The repeatability analysis on normal and pathological subjects results have been compared with literature and found comparable. Normal and pathological gait have been compared and showed major statistically significant differences in the forefoot and midfoot dorsi-plantarflexion.ConclusionEven though various biomechanical models have been developed so far to study the properties and behaviour of the foot, the present study focuses on developing a methodology for the functional assessment of the foot-ankle complex and for the definition of a functional model of the diabetic neuropathic foot. It is, of course, important to evaluate the major sources of variation (true variation in the subject's gait and artefacts from the measurement procedure). The repeatability of the protocol was therefore examined, and results showed the suitability of this method both on normal and pathological subjects. Comparison between normal and pathological kinematics analysis confirmed the validity of a similar approach in order to assess neuropathics biomechanics impairment.

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Immune mediators in patients with acute diabetic foot syndrome.

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Immune mediators in patients with acute diabetic foot syndrome.

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