Soluble RAGE Sequesters Advanced Glycation End Products following an Overnight Fast in T1DM Patients

Context and Objectives: Advanced glycation end products (AGEs) promote the development of diabetic complications through activation of their receptor (RAGE). Isoforms of soluble RAGE (sRAGE) sequester AGEs and thus protect against RAGE-mediated diabetic complications. Low cellular energy, such as during fasting, activates sRAGE production. We investigated the effect of an overnight fast on circulating substrates, hormones, AGEs, and sRAGE isoforms in 26 individuals with type 1 diabetes (T1DM). Participants and Methods: Blood was collected from young (18-30 years) T1DM patients on insulin pumps before and after an overnight fast. Circulating AGEs were measured via LC-MS/MS and sRAGE isoforms were analyzed via ELISA. eGFR cystatin-c was calculated based on circulating cystatin-c measured via ELISA. Results: Glucose, insulin, glucagon, and eGFR cystatin-c decreased while cortisol increased following the overnight fast (p 0.05). AGEs (CML, CEL, 3DG-H, MG-H1, and G-H1) decreased (21-58%, p Conclusions: Following an overnight fast, sRAGE isoforms were increased and sequestered MG-H1. Sequestration of AGEs by sRAGE has been shown to attenuate AGE/RAGE-mediated complications. Energy restriction appears to be important for protection against AGE/RAGE-mediated complications. Disclosure E.R. Miranda: None. K.N. Fuller: None. R. Perkins: None. P.J. Beisswenger: Employee; Self; PreventAGE Health Care, LLC.. S.S. Farabi: None. L.T. Quinn: None. J.M. Haus: None.