title: Glyoxylate, a new marker metabolite of type 2 diabetes.
abstract: Type 2 diabetes (T2D) is characterized by a variety of metabolic impairments that are closely linked to nonenzymatic glycation reactions of proteins and peptides resulting in advanced glycation end-products (AGEs). Reactive aldehydes derived from sugars play an important role in the generation of AGEs. Using metabolite profiling to characterize human plasma from diabetic versus nondiabetic subjects we observed in a recent study that the reactive aldehyde glyoxylate was increased before high levels of plasma glucose, typical for a diabetic condition, could be measured. Following this observation, we explored the relevance of increased glyoxylate in diabetic subjects and in diabetic C57BLKS/J-Lepr (db/db (-/-)) mice in the pathophysiology of diabetes. A retrospective study using samples of long-term blood donors revealed that glyoxylate levels unlike glucose levels became significantly elevated up to 3 years prior to diabetes diagnosis (difference to control P = 0.034). Elevated glyoxylate levels impact on newly identified mechanisms linking hyperglycemia and AGE production with diabetes-associated complications such as diabetic nephropathy. Glyoxylate in its metabolic network may serve as an early marker in diabetes diagnosis with predictive qualities for associated complications and as potential to guide the development of new antidiabetic therapies.
authors.affiliation: Metanomics Health GmbH, 10589 Berlin, Germany ; Timiryazev Institute of Plant Physiology, Russian Academy of Sciences, Moscow 127276, Russia.
authors.forename: Victoria J
authors.initials: VJ
authors.lastname: Nikiforova
authors.affiliation: ZIEL Research Center for Nutrition and Food Sciences, Biochemistry Unit, Technische Universität München, 85354 Freising, Germany.
authors.forename: Pieter
authors.initials: P
authors.lastname: Giesbertz
authors.affiliation: metanomics GmbH, 10589 Berlin, Germany ; Thermo Fisher Scientific, Clinical Diagnostics, BRAHMS GmbH, 16761 Hennigsdorf, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Wiemer
authors.affiliation: metanomics GmbH, 10589 Berlin, Germany.
authors.forename: Bianca
authors.initials: B
authors.lastname: Bethan
authors.affiliation: metanomics GmbH, 10589 Berlin, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Looser
authors.affiliation: Metanomics Health GmbH, 10589 Berlin, Germany ; Thermo Fisher Scientific, Clinical Diagnostics, BRAHMS GmbH, 16761 Hennigsdorf, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Liebenberg
authors.affiliation: Metanomics Health GmbH, 10589 Berlin, Germany ; Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany.
authors.forename: Patricia
authors.initials: P
authors.lastname: Ruiz Noppinger
authors.affiliation: ZIEL Research Center for Nutrition and Food Sciences, Biochemistry Unit, Technische Universität München, 85354 Freising, Germany.
authors.forename: Hannelore
authors.initials: H
authors.lastname: Daniel
authors.affiliation: Metanomics Health GmbH, 10589 Berlin, Germany.
authors.forename: Dietrich
authors.initials: D
authors.lastname: Rein
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D004195:Disease Models, Animal; D005215:Fasting / Q000097:blood; D005838:Genotype; D006038:Glyoxylates / Q000097:blood*; D006801:Humans; D008297:Male; D055432:Metabolomics / Q000379:methods; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000378:metabolism; D010641:Phenotype; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012189:Retrospective Studies; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D006038:Glyoxylates; C031150:glyoxylic acid