25-Hydroxyvitamin D [25(OH)D] levels and diabetic foot ulcer: is there any relationship?

In recent years, there has been an effort to understand possible roles of 25(OH)D, including its role in the immune system particularly on T cell medicated immunity, pancreatic insulin secretion and insulin action. 25(OH)D stimulates the cell differentiation and reduces cell proliferation, which is essential for cell growth and wound healing. However, data on the association between low level of plasma 25(OH)D and diabetic foot syndrome are scarce.

Circulating plasma levels of 25(OH)D were measured in diabetic patients with ulcer (n=162) and without ulcer (n=162) in a prospective cohort hospital based study.

Of these patients, 85.1% had type 2 diabetes. Subjects with diabetic foot ulcer showed lower median plasma level of 25(OH)D [6.3(4.2-11.1) vs 28.0(21.4-37.0)] ng/ml after adjusting the age and BMI. Regardless of the low levels of 25(OH)D in cases and controls, it was associated with neuropathy, sex (female), duration of ulcer healing, and smoking status and independent of confounding factors, including BMI (kg/m²), A1c (%), hypertension, nephropathy, foot ulcer, retinopathy, CAD, PAD, HDL-C (mg/dl) and LDL-C (mg/dl). The factors which predict the risk of developing ulcer independent of 25(OH)D status were A1c (>6.9%) [OR 4.37; RR 1.77], HDL-C (<40mg/dl) [OR 1.16; RR 1.07], LDL-C (>100mg/dl) [OR 1.07; RR 1.03], triglycerides (>200mg/dl) [OR 1.40; RR 1.19], neuropathy [OR 6.88; RR 3.12], retinopathy [OR 3.34; RR 1.91], hypertension [OR 1.64; RR 1.28], nephropathy [OR 3.12; RR 1.87] and smoking [OR 4.53; RR 2.99] using odds and risk ratios.

It is not clear whether the suppression of delayed wound healing seen during 25(OH)D deficiency is due to the secondary effect or is a direct action of vitamin D on certain components of the immune system. Long-term randomized trials are needed to see the impact of vitamin D supplementation on the outcome of diabetic foot patients.