Peer-review started: March 14, 2014
First decision: May 14, 2014
Revised: June 6, 2014
Accepted: August 27, 2014
Article in press: August 31, 2014
Published online: January 18, 2015
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.
Core tip: An immune activation has been reported as important at several stages in the development of chronic wounds of diabetic foot syndrome (DFS). Immune-inflammatory up regulation may precede the incidence of DFS in the same way that it precedes some major cardiovascular diabetic complication such as coronary heart disease as reported by some studies that showed a significant negative correlation of adiponectin plasma levels with cardiovascular risk factors such as hypertension, dyslipidaemia and with previous cerebrovascular events such as previous transient ischemic attack/stroke and new onset events thus underlining the role of hypo-adiponectinaemia as a cardiovascular predictive factor in DFS.