486-P: Reduced Serum Netrin-1 Levels Correlate with Corneal Nerve Fiber Loss in Diabetic Neuropathy

Objective: Deficiency of endogenous neurotropic factors are implicated in diabetic neuropathy (DN). While Netrin-1, a neurotropic factor, is downregulated in type 2 diabetes, its involvement in Diabetic Neuropathy (DN) is yet to be reported. While corneal confocal microscopy (CCM) is a sensitive, in-vivo, non-invasive technique for detection of DN at its earliest stages, the association between CCM parameters and serum Netrin-1 levels has not been reported before. The present study looked at serum netrin levels in populations with type 2 diabetes with or without neuropathy, using CCM as the gold standard.

Methods: Sixty subjects with type 2 diabetes (DN- 30, DN+ 30)] were stratified using DN4Q and Vibration perception Threshold Test (VPT). Cornea was assessed using CCM. Serum Netrin-1 level was measured by ELISA. Data compared 27 healthy controls were also studied.

Results: There was a significant reduction in corneal nerve fibre density (CNFD), branch density (CNBD), and fibre length (CNFL) in T2D. DN was associated with a greater reduction in all CCM parameters compared to those with type 2 diabetes but no DN (p<0.05). There was a progressive decline in the mean serum netrin-1 level from healthy controls to T2D DN- to T2D DN+ (Control vs T2D, p<0.05; T2D DN- vs DN+, p<0.01)]. Netrin-1 correlated only with CNBD in T2D DN- group, (p=0.02). While ROC analysis showed CNFD, CNBD and CNFL to predict DN in 55.6%, 57.1% and 62.1% respectively, Netrin-1 alone predicted DN in 63.3%. CNBD and CNFL correlated with Netrin-1 (p=0.04 and p=0.01) in T2D DN+ group.

Conclusion: Serum netrin-1 levels declined progressively from controls to T2D to T2D with DN; netrin-1 levels correlated significantly with the CCM parameters. Serum Netrin-1 levels showed a significant positive correlation with CNBD in type 2 diabetes (DN- or DN+). A strong correlation was seen between CNFL and netrin-1 levels in more advanced diabetic neuropathy (abnormal VPT). The results of our pilot study need validation in larger populations.