title: DNA Advanced Glycation End Products (DNA-AGEs) Are Elevated in Urine and Tissue in an Animal Model of Type 2 Diabetes.
abstract: More precise identification and treatment monitoring of prediabetic/diabetic individuals will require additional biomarkers to complement existing diagnostic tests. Candidates include hyperglycemia-induced adducts such as advanced glycation end products (AGEs) of proteins, lipids, and DNA. The potential for DNA-AGEs as diabetic biomarkers was examined in a longitudinal study using the Leprdb/dbanimal model of metabolic syndrome. The DNA-AGE, N2-(1-carboxyethyl)-2'-deoxyguanosine (CEdG) was quantified by mass spectrometry using isotope dilution from the urine and tissue of hyperglycemic and normoglycemic mice. Hyperglycemic mice (fasting plasma glucose, FPG, ≥ 200 mg/dL) displayed a higher median urinary CEdG value (238.4 ± 112.8 pmol/24 h) than normoglycemic mice (16.1 ± 11.8 pmol/24 h). Logistic regression analysis revealed urinary CEdG to be an independent predictor of hyperglycemia. Urinary CEdG was positively correlated with FPG in hyperglycemic animals and with HbA1c for all mice. Average tissue-derived CEdG was also higher in hyperglycemic mice (18.4 CEdG/106dG) than normoglycemic mice (4.4 CEdG/106dG). Urinary CEdG was significantly elevated in Leprdb/dbmice relative to Leprwt/wt, and tissue CEdG values increased in the order Leprwt/wt< Leprwt/db< Leprdb/db. These data suggest that urinary CEdG measurement may provide a noninvasive quantitative index of glycemic status and augment existing biomarkers for the diagnosis and monitoring of diabetes.
authors.affiliation: Departments of Molecular Medicine, ‡Biostatistics, and §Cancer Biology, Beckman Research Institute at City of Hope , Duarte, California 91010, United States.
authors.forename: Richard
authors.initials: R
authors.lastname: Jaramillo
authors.affiliation: Departments of Molecular Medicine, ‡Biostatistics, and §Cancer Biology, Beckman Research Institute at City of Hope , Duarte, California 91010, United States.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Shuck
authors.affiliation: Departments of Molecular Medicine, ‡Biostatistics, and §Cancer Biology, Beckman Research Institute at City of Hope , Duarte, California 91010, United States.
authors.forename: Yin S
authors.initials: YS
authors.lastname: Chan
authors.affiliation: Departments of Molecular Medicine, ‡Biostatistics, and §Cancer Biology, Beckman Research Institute at City of Hope , Duarte, California 91010, United States.
authors.forename: Xueli
authors.initials: X
authors.lastname: Liu
authors.affiliation: Departments of Molecular Medicine, ‡Biostatistics, and §Cancer Biology, Beckman Research Institute at City of Hope , Duarte, California 91010, United States.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Bates
authors.affiliation: Departments of Molecular Medicine, ‡Biostatistics, and §Cancer Biology, Beckman Research Institute at City of Hope , Duarte, California 91010, United States.
authors.forename: Punnajit P
authors.initials: PP
authors.lastname: Lim
authors.affiliation: Departments of Molecular Medicine, ‡Biostatistics, and §Cancer Biology, Beckman Research Institute at City of Hope , Duarte, California 91010, United States.
authors.forename: Daniel
authors.initials: D
authors.lastname: Tamae
authors.affiliation: Departments of Molecular Medicine, ‡Biostatistics, and §Cancer Biology, Beckman Research Institute at City of Hope , Duarte, California 91010, United States.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Lacoste
authors.affiliation: Departments of Molecular Medicine, ‡Biostatistics, and §Cancer Biology, Beckman Research Institute at City of Hope , Duarte, California 91010, United States.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: O'Connor
authors.affiliation: Departments of Molecular Medicine, ‡Biostatistics, and §Cancer Biology, Beckman Research Institute at City of Hope , Duarte, California 91010, United States.
authors.forename: John
authors.identifier: 0000-0002-4043-7552
authors.initials: J
authors.lastname: Termini
mesh_terms: D000818:Animals; D004247:DNA / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004195:Disease Models, Animal; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D017127:Glycation End Products, Advanced; D004247:DNA