In conclusion, the activation of RAGE signaling through chronic hyperglycemia skews the polarity of macrophages toward the proinflammatory M1 phenotype, which induces local inflammation in the SN, disturbing RAT and insulin signaling and resulting in the development of early neuropathy in experimental T1D (Supplemental Figure 9, B and C). The gene discussed is AGER; the disease is Hyperglycemia.