In a former case-control study enrolling 53 healthy controls, 46 patients with T2DM and peripheral diabetic neuropathy (DN), and 53 patients with T2DM without DN, it was shown that: (1) patients with T2DM and DN had significantly higher circulating endocan levels compared to healthy controls, and (2) patients with T2DM and DN also had significantly higher circulating endocan levels than subjects without underlying DN, suggesting an emerging role of endocan in several mechanisms implicated into DN pathogenesis, including endothelial dysfunction, angiogenesis, and inflammation [47]. This evidence concerns the gene ESM1 and type 2 diabetes mellitus.