Aims/Hypothesis: Netrin-1 has been introduced as a neuronal guidance cue, acting as a chemoattractant and chemorepulsive force during axonal migration. In recent studies, netrin-1 was shown to play various roles including tissue regeneration and modulation of inflammatory action. Inflammation is one of the major contributing factors in the development of insulin resistance and type 2 diabetes (T2DM). However, little is known about the possible relationship between serum netrin-1 and the risk of T2DM. Therefore, we investigated the association between levels of netrin-1 and glycometabolic parameters.

Methods: Serum samples were collected from a total of 218 individuals (41 normal controls, 85 subjects with impaired fasting glucose (IFG) and 92 subjects with newly diagnosed T2DM). Clinical and biochemical parameters were assessed after receiving consent. Netrin-1 levels were determined by commercial enzyme-linked immunosorbent assay. Spearman correlation analyses and multivariable-adjusted linear regression analyses were conducted to examine the relationship between serum netrin-1 levels and glycometabolic parameters.

Results: Serum netrin-1 level in subjects with IFG or T2DM was significantly higher than in normal control subjects (mean netrin-1 level; normal, IFG and T2DM; 275.9, 436.6 and 441.0 pg/mL, respectively; p for trend <0.001). Serum netrin-1 levels had a significant positive correlation with fasting glucose, HbA1c, HOMA-IR, AST and ALT. Meanwhile, statistically inverse correlation was found between netrin-1 and HDL cholesterol and eGFR levels. In addition, Serum netrin-1 was independently associated with the presence of IFG or T2DM after adjusting covariates and potential confounders. In terms of the AUC, serum netrin-1 levels presented an AUC of 0.784 for the prediction of IFG or T2DM.

Conclusions/Interpretation: Our results suggest that netrin-1 may be a new biomarker for early detection for IFG or T2DM (Clinical trial no. NCT02650830).


H. Jung: None. J. Bae: None. E. Han: None. G. Kim: None. J. Lee: None. S. Kim: None. B. Lee: None. E. Kang: None. C. Ahn: None. B. Cha: None. Y. Lee: None.

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