Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Masania, J; Faustmann, G; Anwar, A; Hafner-Giessauf, H; Rajpoot, N; Grabher, J; Rajpoot, K; Tiran, B; Obermayer-Pietsch, B; Winklhofer-Roob, BM; Roob, JM; Rabbani, N; Thornalley, PJ.
Urinary Metabolomic Markers of Protein Glycation, Oxidation, and Nitration in Early-Stage Decline in Metabolic, Vascular, and Renal Health.
OXID MED CELL LONGEV. 2019; 2019(6): 4851323-4851323.
Doi: 10.1155/2019/4851323
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- Co-Autor*innen der Med Uni Graz
- Faustmann Gernot
- Grabher Johanna
- Hafner-Giessauf Hildegard Elisabeth
- Obermayer-Pietsch Barbara
- Roob Johannes
- Tiran Beate
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- Abstract:
- Glycation, oxidation, nitration, and crosslinking of proteins are implicated in the pathogenic mechanisms of type 2 diabetes, cardiovascular disease, and chronic kidney disease. Related modified amino acids formed by proteolysis are excreted in urine. We quantified urinary levels of these metabolites and branched-chain amino acids (BCAAs) in healthy subjects and assessed changes in early-stage decline in metabolic, vascular, and renal health and explored their diagnostic utility for a noninvasive health screen. We recruited 200 human subjects with early-stage health decline and healthy controls. Urinary amino acid metabolites were determined by stable isotopic dilution analysis liquid chromatography-tandem mass spectrometry. Machine learning was applied to optimise and validate algorithms to discriminate between study groups for potential diagnostic utility. Urinary analyte changes were as follows: impaired metabolic health-increased N ε -carboxymethyl-lysine, glucosepane, glutamic semialdehyde, and pyrraline; impaired vascular health-increased glucosepane; and impaired renal health-increased BCAAs and decreased N ε -(γ-glutamyl)lysine. Algorithms combining subject age, BMI, and BCAAs discriminated between healthy controls and impaired metabolic, vascular, and renal health study groups with accuracy of 84%, 72%, and 90%, respectively. In 2-step analysis, algorithms combining subject age, BMI, and urinary N ε -fructosyl-lysine and valine discriminated between healthy controls and impaired health (any type), accuracy of 78%, and then between types of health impairment with accuracy of 69%-78% (cf. random selection 33%). From likelihood ratios, this provided small, moderate, and conclusive evidence of early-stage cardiovascular, metabolic, and renal disease with diagnostic odds ratios of 6 - 7, 26 - 28, and 34 - 79, respectively. We conclude that measurement of urinary glycated, oxidized, crosslinked, and branched-chain amino acids provides the basis for a noninvasive health screen for early-stage health decline in metabolic, vascular, and renal health. Copyright © 2019 Jinit Masania et al.