Evaluation of Serum Netrin-1 as a Novel Biomarker for Type 2 Diabetes Mellitus: A Cross-sectional Study

Background: Netrin-1, a protein known for its anti-inflammatory, tissue-regenerative, and immune-modulatory effects, has been shown to play a role in various biological processes.While inflammation is a key factor in the onset of insulin resistance and type 2 diabetes mellitus (T2DM), there is a lack of data regarding the potential link between serum Netrin-1 levels and T2DM.In this study, we aimed to explore the relationship between circulating Netrin-1 concentrations and metabolic indicators that are predictive of T2DM.Aim: To assess, compare, and correlate serum Netrin-1 levels, fasting glucose, glycated hemoglobin A1c (HbA1c), homeostasis model of insulin resistance (HOMA-IR), and lipid profile in pre-diabetes mellitus (pre-DM), newly diagnosed T2DM, and healthy controls.Methods: This is a cross-sectional case-control study including 45 cases with pre-DM, 60 cases with DM, and 40 healthy controls.Results: The median serum Netrin-1 (pg/mL) levels in controls, pre-DM, and DM cases were 102 (126.6-87.34),295.4 (370-234.8),and 766.7 (969.1-506.2),respectively.There was a significant positive correlation between serum Netrin-1 and HbA1c, fasting plasma glucose, HOMA-IR, body mass index (BMI), total cholesterol, low-density lipoprotein cholesterol, triglycerides, aspartate transaminase, and alanine transaminase (p < 0.05).On receiver operating characteristic curve analysis, serum Netrin-1 has a sensitivity of 95% and specificity of 90.48% at a cut-off of 169.3 pg/mL in predicting impaired fasting glucose (IFG) or T2DM.Conclusion: Elevated serum Netrin-1 levels indicate that it could be used as an additional marker for early detection of IFG and inflammation in DM.Clinical significance: Our study has shown that elevated levels of serum Netrin-1 correlate with the degree of hyperglycemia and control of glucose levels may halt or delay further development of inflammatory changes involved in DM and its complications.