Circulating netrin‐1 levels are reduced and related to corneal nerve fiber loss in patients with diabetic neuropathy

Abstract

Abstract Aims/Introduction Deficiency of neurotropic factors is implicated in diabetic neuropathy (DN). Netrin‐1 is a neurotropic factor, but its association with DN has not been explored. We have assessed the association between serum netrin‐1 levels and early diabetic neuropathy assessed by quantifying corneal nerve fiber loss using corneal confocal microscopy. Materials and Methods A total of 72 participants with type 2 diabetes, without and with corneal nerve fiber loss (DN− n = 42, DN+ n = 30), and 45 healthy controls were studied. Serum netrin‐1 levels were measured by enzyme‐linked immunosorbent assay, and corneal nerve morphology was assessed using corneal confocal microscopy. Results Corneal nerve fiber density, branch density, fiber length and serum netrin‐1 levels were significantly lower in the DN− and DN+ groups compared with controls (P < 0.001). Netrin‐1 levels correlated with corneal nerve fiber length in the DN+ group (r = 0.51; P < 0.01). A receiver operating characteristic curve analysis showed that a netrin‐1 cut‐off value of 599.6 (pg/mL) had an area under the curve of 0.85, with a sensitivity of 76% and specificity of 74% (P < 0.001; 95% confidence interval 0.76–0.94) for differentiating patients with and without corneal nerve loss. Conclusions Serum netrin‐1 levels show a progressive decline with increasing severity of small nerve fiber damage in patients with diabetes. Netrin‐1 could act as a biomarker for small nerve fiber damage in DN.

Keywords

• Corneal confocal microscopy
• Diabetic neuropathy
• Netrin‐1