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/db animal model of metabolic syndrome. The DNA-AGE, N2(1-carboxyethyl)-2′-deoxyguanosine (CEdG) was quantified by mass spectrometry using isotope dilution from 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/106 dG) than normoglycemic mice (4.4 CEdG/106 dG). Urinary CEdG was significantly elevated in Leprdb/db mice 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 non-invasive quantitative index of glycemic status and augment existing biomarkers for the diagnosis and monitoring of diabetes.

Advanced glycosylated end products restrain the osteogenic differentiation of the periodontal ligament stem cell

“…Previous studies on the relationship between chronic adult periodontitis and diabetes mellitus have found that locally deposited AGEs can reduce the production of the extracellular matrix, decrease the expression of collagen, hinder the differentiation and maturation of osteoblasts, mediate the apoptosis and delay the repair of the periodontal tissues 29, 30, 31. Our investigation found that AGEs significantly inhibit bone differentiation of the PDLSCs in a dose-dependant manner.…”

The Role of Advanced Glycation End Products in Aging and Metabolic Diseases: Bridging Association and Causality

“…DNA-AGEs such as N 2 (1-carboxyethyl)-2’-deoxyguanosine (CEdG) has been described as a potential biomarker of chronic hyperglycemia in mice. CEdG levels are significantly elevated in urine collected from hyperglycemic Lepr db/db mice compared to normoglycemic control mice (Jaramillo et al, 2017). Of note, many of the same compounds are produced in baked and roasted foods (Delgado-Andrade and Fogliano, 2018).…”

Hyperglycemia Associated Metabolic and Molecular Alterations in Cancer Risk, Progression, Treatment, and Mortality

“…Oxidized bases, if not repaired, lead to mutations which can trigger oncogenes or deactivate tumor suppressor genes, causing initiation and/or progression of different cancers [26,27]. Methylglyoxal induced AGE accumulation in tissues may occur even in a relatively mild diabetic condition and cause DNA damage [28]. Avoiding sweetened foods and drinks is often recommended for inhibiting glycation product formation and accumulation, thereby highlighting the role of hyperglycemia in DNA damage [24].…”