Publication Description
Abstract Purpose We determined the association between novel and acid-labile skin collagen-linked advanced glycation endproducts (AGEs) and the progression of microvascular and neuropathic complications from baseline to near study closeout in the Diabetes Control and Complications Trial (DCCT). Methods From a skin biopsy obtained near the close of the DCCT, proteolytic collagen digests were analyzed by liquid chromatography/mass spectrometry (LC/MS/MS) for glucosepane (GSPNE), glyoxal and methylglyoxal hydroimidazolones (G-H1 and MG-H1) and the glycation product fructose-lysine (FL) using isotope dilution method. Results GSPNE and MG-H1 correlated with age and diabetes duration (P 40 mg/24 h (OR = 5.3, P < 0.0001), and confirmed clinical neuropathy (OR = 3.4, P = 0.015) at the time of the biopsy. GSPNE adjusted for mean A1c remained significant for ≥ 3 MA (P = 0.0252) and AER (P = 0.0006). The strong association of complications with A1c was reduced or eliminated when adjusted for GSPNE. Conclusions Glucosepane is a novel AGE marker of diabetic complications that is robustly associated with nephropathic, retinopathic and neuropathic outcomes despite adjustment for A1c, suggesting that it could be one mediator of these complications with possible diagnostic implications.