title: Glycation sites of human plasma proteins are affected to different extents by hyperglycemic conditions in type 2 diabetes mellitus.
abstract: Glucose can modify proteins in human blood, forming early glycation products (e.g., Amadori compounds), which can slowly degrade to advanced glycation endproducts (AGEs). AGEs contribute significantly to complications of diabetes mellitus and, thus, represent markers of advanced disease stages. They are, however, currently unsuitable for early diagnosis and therapeutic monitoring. Here, we report sensitive strategies to identify and relatively quantify protein glycation sites in human plasma samples obtained from type 2 diabetes mellitus (T2DM) patients and age-matched nondiabetic individuals using a bottom-up approach. Specifically, Amadori peptides were enriched from tryptic digests by boronic acid affinity chromatography, separated by reversed-phase chromatography, and analyzed on-line by high-resolution mass spectrometry. Among the 52 Amadori peptides studied here were 20 peptides resembling 19 glycation sites in six human proteins detected at statistically significantly higher levels in T2DM than in the normoglycemic controls. Four positions appeared to be unique for T2DM within the detection limit. All 19 glycation sites represent promising new biomarker candidates for early diagnosis of T2DM and adequate therapeutic control, as they may indicate early metabolic changes preceding T2DM.
authors: Institute of Bioanalytical Chemistry, Faculty of Chemistry and Mineralogy, Johannisallee 29, 04103, Leipzig, Germany.
authors: Andrej
authors: A
authors: Frolov
authors: Matthias
authors: M
authors: Blüher
authors: Ralf
authors: R
authors: Hoffmann
mesh_terms: D000328:Adult; D020816:Amino Acid Motifs; D001798:Blood Proteins / Q000737:chemistry / Q000378:metabolism*; D016022:Case-Control Studies; D002846:Chromatography, Affinity; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D006031:Glycosylation; D006801:Humans; D006943:Hyperglycemia / Q000097:blood*; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged
chemical_list: D001798:Blood Proteins