Lipoprotein(a) and homocysteine as genetic risk factors for vascular and neuropathic diabetic foot in type 2 diabetes mellitus

Neuropathy and peripheral artery disease represent the main pathophysiological conditions underlying diabetic foot. Several studies showed that Lipoprotein(a)-Lp(a)-and homocysteine (Hcy) can be associated with diabetic complications, but their relationship with diabetic foot is unclear. Aim of this study was to investigate whether Lp(a) and Hcy were associated with diabetic foot ulcerations, classified according to the presence of peripheral artery disease (PAD) or neuropathy. From among consecutive type 2 diabetic attending at the Diabetic Foot Clinic 27 subjects with vascular diabetic foot (VDF), 43 with neuropathic diabetic foot (NDF) and 52 controls without foot ulceration, neuropathy, and PAD were enrolled. Both Lp(a) (26.1 ± 22.7 vs. 14.9 ± 19.5 mg/dl; P = 0.003) and Hcy levels (15.4 ± 5.7 vs. 12.2 ± 5.1 μmol/l; P = 0.022) were significantly greater in the VDF group than in controls. Lp(a) levels were significantly lower in the NDF group than in controls (6.9 ± 8.1 versus 14.9 ± 19.5 mg/dl; P = 0.009), while no difference in Hcy levels was found. Multiple logistic regression analysis showed that Hcy was associated with VDF (OR: 1.11; 95% CI: 1.07-14.1; P = 0.048). Lp(a) did not enter the model, but its P-value was very near to the significant level (OR: 1.09; 95% CI: 0.99-12.05; P = 0.059). Moreover, low Lp(a) levels were associated with NDF (OR: 0.84; 95% CI: 0.21-0.96; P = 0.039). Our study has shown for the first time that high Lp(a) and Hcy levels are associated with the development of VDF, while low Lp(a) levels appear to be associated with delayed wound healing in patients with neuropathic foot ulcerations.