Urinary Metabolomic Markers of Protein Glycation, Oxidation, and Nitration in Early-Stage Decline in Metabolic, Vascular, and Renal Health
<p>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 m...
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| مؤلفون آخرون: | , , , , , , , , , , , |
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2019
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| _version_ | 1864513554074304512 |
|---|---|
| author | Jinit Masania (7164239) |
| author2 | Gernot Faustmann (5497745) Attia Anwar (3484340) Hildegard Hafner-Giessauf (14590917) Nasir Rajpoot (781022) Johanna Grabher (14590920) Kashif Rajpoot (781020) Beate Tiran (239387) Barbara Obermayer-Pietsch (61534) Brigitte M. Winklhofer-Roob (239389) Johannes M. Roob (239381) Naila Rabbani (291722) Paul J. Thornalley (14590926) |
| author2_role | author author author author author author author author author author author author |
| author_facet | Jinit Masania (7164239) Gernot Faustmann (5497745) Attia Anwar (3484340) Hildegard Hafner-Giessauf (14590917) Nasir Rajpoot (781022) Johanna Grabher (14590920) Kashif Rajpoot (781020) Beate Tiran (239387) Barbara Obermayer-Pietsch (61534) Brigitte M. Winklhofer-Roob (239389) Johannes M. Roob (239381) Naila Rabbani (291722) Paul J. Thornalley (14590926) |
| author_role | author |
| dc.creator.none.fl_str_mv | Jinit Masania (7164239) Gernot Faustmann (5497745) Attia Anwar (3484340) Hildegard Hafner-Giessauf (14590917) Nasir Rajpoot (781022) Johanna Grabher (14590920) Kashif Rajpoot (781020) Beate Tiran (239387) Barbara Obermayer-Pietsch (61534) Brigitte M. Winklhofer-Roob (239389) Johannes M. Roob (239381) Naila Rabbani (291722) Paul J. Thornalley (14590926) |
| dc.date.none.fl_str_mv | 2019-11-19T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1155/2019/4851323 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Urinary_Metabolomic_Markers_of_Protein_Glycation_Oxidation_and_Nitration_in_Early-Stage_Decline_in_Metabolic_Vascular_and_Renal_Health/22082720 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Biochemistry and cell biology Bioinformatics and computational biology Biomedical and clinical sciences Clinical sciences Medical biochemistry and metabolomics Cell Biology Aging General Medicine Biochemistry |
| dc.title.none.fl_str_mv | Urinary Metabolomic Markers of Protein Glycation, Oxidation, and Nitration in Early-Stage Decline in Metabolic, Vascular, and Renal Health |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p>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<em>ε</em>-carboxymethyl-lysine, glucosepane, glutamic semialdehyde, and pyrraline; impaired vascular health—increased glucosepane; and impaired renal health—increased BCAAs and decreased N<em>ε</em>-(<em>γ</em>-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<em>ε</em>-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% (<em>cf.</em> 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. </p> <h2>Other information</h2> <p>Published in: Oxidative Medicine and Cellular Longevity<br> License: <a href="http://creativecommons.org/licenses/by/4.0" target="_blank">http://creativecommons.org/licenses/by/4.0</a><br> See article on publisher's website: <a href="http://dx.doi.org/10.1155/2019/4851323" target="_blank">http://dx.doi.org/10.1155/2019/4851323</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_54bb5091e6e64d82a2b7ff634f9a79ed |
| identifier_str_mv | 10.1155/2019/4851323 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/22082720 |
| publishDate | 2019 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Urinary Metabolomic Markers of Protein Glycation, Oxidation, and Nitration in Early-Stage Decline in Metabolic, Vascular, and Renal HealthJinit Masania (7164239)Gernot Faustmann (5497745)Attia Anwar (3484340)Hildegard Hafner-Giessauf (14590917)Nasir Rajpoot (781022)Johanna Grabher (14590920)Kashif Rajpoot (781020)Beate Tiran (239387)Barbara Obermayer-Pietsch (61534)Brigitte M. Winklhofer-Roob (239389)Johannes M. Roob (239381)Naila Rabbani (291722)Paul J. Thornalley (14590926)Biological sciencesBiochemistry and cell biologyBioinformatics and computational biologyBiomedical and clinical sciencesClinical sciencesMedical biochemistry and metabolomicsCell BiologyAgingGeneral MedicineBiochemistry<p>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<em>ε</em>-carboxymethyl-lysine, glucosepane, glutamic semialdehyde, and pyrraline; impaired vascular health—increased glucosepane; and impaired renal health—increased BCAAs and decreased N<em>ε</em>-(<em>γ</em>-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<em>ε</em>-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% (<em>cf.</em> 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. </p> <h2>Other information</h2> <p>Published in: Oxidative Medicine and Cellular Longevity<br> License: <a href="http://creativecommons.org/licenses/by/4.0" target="_blank">http://creativecommons.org/licenses/by/4.0</a><br> See article on publisher's website: <a href="http://dx.doi.org/10.1155/2019/4851323" target="_blank">http://dx.doi.org/10.1155/2019/4851323</a></p>2019-11-19T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1155/2019/4851323https://figshare.com/articles/journal_contribution/Urinary_Metabolomic_Markers_of_Protein_Glycation_Oxidation_and_Nitration_in_Early-Stage_Decline_in_Metabolic_Vascular_and_Renal_Health/22082720CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/220827202019-11-19T03:00:00Z |
| spellingShingle | Urinary Metabolomic Markers of Protein Glycation, Oxidation, and Nitration in Early-Stage Decline in Metabolic, Vascular, and Renal Health Jinit Masania (7164239) Biological sciences Biochemistry and cell biology Bioinformatics and computational biology Biomedical and clinical sciences Clinical sciences Medical biochemistry and metabolomics Cell Biology Aging General Medicine Biochemistry |
| status_str | publishedVersion |
| title | Urinary Metabolomic Markers of Protein Glycation, Oxidation, and Nitration in Early-Stage Decline in Metabolic, Vascular, and Renal Health |
| title_full | Urinary Metabolomic Markers of Protein Glycation, Oxidation, and Nitration in Early-Stage Decline in Metabolic, Vascular, and Renal Health |
| title_fullStr | Urinary Metabolomic Markers of Protein Glycation, Oxidation, and Nitration in Early-Stage Decline in Metabolic, Vascular, and Renal Health |
| title_full_unstemmed | Urinary Metabolomic Markers of Protein Glycation, Oxidation, and Nitration in Early-Stage Decline in Metabolic, Vascular, and Renal Health |
| title_short | Urinary Metabolomic Markers of Protein Glycation, Oxidation, and Nitration in Early-Stage Decline in Metabolic, Vascular, and Renal Health |
| title_sort | Urinary Metabolomic Markers of Protein Glycation, Oxidation, and Nitration in Early-Stage Decline in Metabolic, Vascular, and Renal Health |
| topic | Biological sciences Biochemistry and cell biology Bioinformatics and computational biology Biomedical and clinical sciences Clinical sciences Medical biochemistry and metabolomics Cell Biology Aging General Medicine Biochemistry |