Divergent Changes in Plasma AGEs and sRAGE Isoforms Following an Overnight Fast in T1DM.
2019 Feb 13;11(2)pii: E386. doi: 10.3390/nu11020386
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 protect against RAGE-mediated diabetic complications. We investigated the effect of an overnight fast on circulating metabolic substrates, hormones, AGEs, and sRAGE isoforms in 26 individuals with type 1 diabetes (T1DM). Blood was collected from 26 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. Glucose, insulin, glucagon, and eGFR decreased while cortisol increased following the overnight fast ( 0.05). AGEs (CML, CEL, 3DG-H, MG-H1, and G-H1) decreased (21⁻58%, < 0.0001) while total sRAGE, cleaved RAGE (cRAGE), and endogenous secretory RAGE (esRAGE) increased (22⁻24%, < 0.0001) following the overnight fast. The changes in sRAGE isoforms were inversely related to MG-H1 ( = -0.493 to -0.589, < 0.05) and the change in esRAGE was inversely related to the change in G-H1 ( = -0.474, < 0.05). Multiple regression analyses revealed a 1 pg/mL increase in total sRAGE, cRAGE, or esRAGE independently predicted a 0.42⁻0.52 nmol/L decrease in MG-H1. Short-term energy restriction via an overnight fast resulted in increased sRAGE isoforms and may be protective against AGE accumulation.
Nutrients|2019 Feb 13