In this study, we compared the development of PNS and CNS neuropathy in two strains of mice with type 1 insulin-deficient or type 2/obesity insulin-resistant diabetes or pre-diabetes and found that, independent of glucose level and in addition to the insulin signaling impairment, lipid and adiponectin profiles can determine the phenotype of the neuropathy. Here, ADIPOQ is linked to obesity due to melanocortin 4 receptor deficiency.