Diabetes mellitus presents either as Type 1, where the pancreas fails to produce insulin, or Type 2, where the body fails to respond to insulin. The altered physiology seen in diabetes can produce widespread effects including cardiovascular dysfunction and poor healing. Wound infection is seen more often in patients with diabetes and healing can be substantially delayed.
A review of 790 orthopaedic patients showed those with blood glucose levels of ≥200mg/dL had an odds ratio of 2.7 (95% CI 1.1-6.7) for thirty-day surgical site infection. Those with a hyperglycaemic index of ≥1.76 had an odds ration of 4.9 (95%CI 2.0-11.8) for thirty-day surgical site infection (Richards et al., 2012).
A study of 80 patients undergoing abdominoperineal resection showed perineal wound complications in 67% of diabetics and 18% of controls (p=0.04) (Matsuda et al., 2009).
One key mediator is Nitric Oxide. Deficiency of nitric oxide increases vascular resistance and promotes atherogenesis, impairing the mobilisation of endothelial progenitor cells necessary for angiogenesis in wound healing.
A study of diabetic rats showed a specific glucose-induced impairment in nitric oxide synthesis while incubation of human cells with an antioxidant reversed this effect. The conclusion was that a glucose-induced impairment in nitric oxide production may contribute to endothelial vascular dysfunction (Lin et al., 2002).
A study of diabetic rats showed uncoupling of endothelial nitric oxide synthase, with production of superoxide anions instead of nitric oxide. Similar effects were shown in diabetic human bone marrow. The conclusion was that this effect is likely to contribute to the pathogenesis of vascular disease in diabetes (Thum et al., 2007).
Effective resolution of the inflammatory phase of wound healing requires clearance of dead cells (efferocytosis). Macrophages undertake this task, but are dysfunctional in diabetes. The result is residual exposure of the healing wound to the toxic contents of dead and dying cells, persistent inflammation and delayed healing.
A study of diabetic mice showed macrophages isolated from wounds had impaired efferocytosis, with an associated higher burden of apoptotic cells and higher expression of pro-inflammatory and lower expression of anti-inflammatory cytokines. The conclusion was that diabetic wounds suffer from dysfunctional macrophage efferocytosis, prolonging the inflammatory phase and complicating wound healing (Khanna et al., 2010).