Role of neuropathy and plasma nitric oxide in recurrent neuropathic and neuroischemic diabetic foot ulcers.

Various factors are associated with foot ulceration, including delayed reporting of ulcers, poor glycemic control, and severity of neuropathy. Several studies have looked at the role of nitric oxide in wound healing. However, no studies have examined its role in the occurrence and recurrence of diabetic foot ulceration. In a cross-sectional study we examined the role of neuropathy, retinopathy, nephropathy, and plasma nitric oxide (estimated from plasma nitrite and nitrate) levels in diabetic patients with recurrent and non-recurrent neuropathic and neuroischemic foot ulcers. Patients with recurrent foot ulcers had higher vibration perception threshold values compared to patients with non-recurrent foot ulcers (47.4 +/- 5.7 volts versus 39.5 +/- 10.3 volts respectively, P < 0.05). In addition, subjects with recurrent foot ulcers had significantly higher plasma nitric oxide compared to subjects with non-recurrent foot ulcers (46.9 +/- 6.3 microm/L versus 30.2 +/- 2.4 microm/L respectively, P < 0.01). Multivariate logistic regression analysis adjusted for age, sex, hemoglobin A1c, presence of retinopathy and nephropathy, vibration perception threshold, plasma creatinine, and total nitric oxide, indicated that only vibration perception threshold was independently associated with the presence of an ulcer [odds ratio: 1.26 (1.10-1.46); P <0.001)] and the recurrence of foot ulcers [odds ratio: 1.13 (1.01-1.27); P =0.04)]. This study has shown that although plasma nitric oxide is higher in patients with recurrent neuropathic and neuroischemic foot ulcers, severity of neuropathy was the most important factor associated with the development and recurrence of foot ulcers in diabetic patients.