Site‐specific arginine dicarbonyl modifications of serum albumin are reduced in metformin‐controlled T2DM patients

Abstract

Advanced glycation end products (AGE) are a possible link between hyperglycemia and the development of diabetic complications. Careful control of AGE could be vital to improve diabetic complications. Biomarkers to evaluate control of AGE are needed to guide development of emerging therapies. Using an unbiased proteomics approach, dicarbonyl (methylglyoxal, glucosone, and 3‐deoxyglucosone) on arginine (R) and oxidative markers on methionine residues on serum albumin were studied in 120 subjects with varying degrees of type‐2 diabetes mellitus (T2DM) with or without metformin treatment. Trypsin digested delipidated serum samples were analyzed by multiple reaction monitoring on a QTRAP mass spectrometer, based on transitions that were validated in vitro. Strong signals for dicarbonyl modification were observed at R186, R257, and R428. Statistical analyses of the dicarbonyl‐R in relation to known T2DM clinical markers including HbA1c, fasting glucose, and waist circumference were performed between groups. Dicarbonyl markers were significantly higher in T2DM (n=47) compared to non‐T2DM (n=46), and certain markers were significantly decreased in T2DM/metformin compared to T2DM (n=26; p<0.001 [post hoc]). The study reveals that dicarbonyl adducts may be a useful biomarker for monitoring the progression of T2DM and metformin treatment efficacy. (P30ES006694, R24DK083948, T32ES016652, T32ES007091).