Numerous studies showed that decreased Nrg4 levels were closely associated with obesity, insulin resistance, diabetes mellitus, dyslipidemia, metabolic syndrome, non-alcoholic fatty liver disease, inflammation, oxidative stress, and macrovascular disease such as coronary artery disease, myocardial infarcts, subclinical cardiovascular disease (CVD) in rodents and humans [3, 5–15], while all above factors have been reported to contribute to the development of DNP [1–3, 16, 17], suggesting indirectly that Nrg4 appears to play a crucial role in the development of DNP. This evidence concerns the gene NRG4 and diabetes mellitus.