Even though there is no currently defined model to explain the increased affinity of Ntn1 and its receptor (Unc5b) in individuals with T2D, we propose a possible explanation for this phenomenon: the existence and development of resistance or loss of affinity may lead to the hypersecretion of Ntn1 without negative feedback, therefore increasing the concentration of pro-inflammatory cytokines and perpetuating the inflammatory status (as measured by serum concentration of hsCRP), which will provoke an increase in NF-kB activity, thus causing more inflammation. This evidence concerns the gene NTN1 and type 2 diabetes mellitus.