Metabolomic Assessment Reveals Alteration in Polyols and Branched Chain Amino Acids Associated With Present and Future Renal Impairment in a Discovery Cohort of 637 Persons With Type 1 Diabetes
Background: Improved understanding of the pathophysiology causing diabetic kidney disease (DKD) is imperative. The aim of this study was to uncover associations between serum metabolites and renal outcomes.Methods: Non-targeted serum metabolomics analyses were performed in samples from 637 persons w...
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| Format: | Article |
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Frontiers Media S.A.
2019-11-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fendo.2019.00818/full |
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| author | Nete Tofte Tommi Suvitaival Kajetan Trost Ismo Matias Mattila Simone Theilade Signe Abitz Winther Signe Abitz Winther Tarunveer Singh Ahluwalia Marie Frimodt-Møller Cristina Legido-Quigley Cristina Legido-Quigley Peter Rossing Peter Rossing |
| author_facet | Nete Tofte Tommi Suvitaival Kajetan Trost Ismo Matias Mattila Simone Theilade Signe Abitz Winther Signe Abitz Winther Tarunveer Singh Ahluwalia Marie Frimodt-Møller Cristina Legido-Quigley Cristina Legido-Quigley Peter Rossing Peter Rossing |
| author_sort | Nete Tofte |
| collection | DOAJ |
| description | Background: Improved understanding of the pathophysiology causing diabetic kidney disease (DKD) is imperative. The aim of this study was to uncover associations between serum metabolites and renal outcomes.Methods: Non-targeted serum metabolomics analyses were performed in samples from 637 persons with type 1 diabetes using two-dimensional gas chromatography coupled to time-of-flight mass-spectrometry. Longitudinal data at follow-up (median 5.5 years) on renal events were obtained from national Danish health registries. A composite renal endpoint (n = 123) consisted of estimated glomerular filtration rate (eGFR) decline from baseline (≥30%), progression to end-stage renal disease and all-cause mortality. Metabolites with significant associations (p < 0.05) in any of the cross-sectional analyses with eGFR and albuminuria were analyzed for specific and composite endpoints. Adjustments included traditional cardiovascular risk factors and correction for multiple testing.Results: A data-driven partial correlation analysis revealed a dense fabric of co-regulated metabolites and clinical variables dominated by eGFR. Ribonic acid and myo-inositol were inversely associated with eGFR, positively associated with macroalbuminuria (p < 0.02) and longitudinally associated with higher risk of eGFR decline ≥30% (HR 2.2–2.7, CI [1.3–4.3], p < 0.001). Ribonic acid was associated with a combined renal endpoint (HR 1.8, CI [1.3–2.3], p = 0.001). The hydroxy butyrate 3,4-dihydroxybutanoic acid was cross-sectionally associated with micro- and macroalbuminuria, urinary albumin excretion rate and inversely associated with eGFR (p < 0.04) while branched chain amino acids were associated with eGFR and lower risk of the combined renal endpoint (p < 0.02).Conclusions: Alterations in serum metabolites, particularly polyols and amino acids, were associated with renal endpoints in type 1 diabetes highlighting molecular pathways associated with progression of kidney disease. External validation is needed to further assess their roles and potentials as future therapeutic targets. |
| first_indexed | 2024-12-23T13:22:01Z |
| format | Article |
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| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-23T13:22:01Z |
| publishDate | 2019-11-01 |
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| series | Frontiers in Endocrinology |
| spelling | doaj.art-743c026f926745369b3db21e4bb00fef2022-12-21T17:45:25ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922019-11-011010.3389/fendo.2019.00818491778Metabolomic Assessment Reveals Alteration in Polyols and Branched Chain Amino Acids Associated With Present and Future Renal Impairment in a Discovery Cohort of 637 Persons With Type 1 DiabetesNete Tofte0Tommi Suvitaival1Kajetan Trost2Ismo Matias Mattila3Simone Theilade4Signe Abitz Winther5Signe Abitz Winther6Tarunveer Singh Ahluwalia7Marie Frimodt-Møller8Cristina Legido-Quigley9Cristina Legido-Quigley10Peter Rossing11Peter Rossing12Steno Diabetes Center Copenhagen, Gentofte, DenmarkSteno Diabetes Center Copenhagen, Gentofte, DenmarkSteno Diabetes Center Copenhagen, Gentofte, DenmarkSteno Diabetes Center Copenhagen, Gentofte, DenmarkSteno Diabetes Center Copenhagen, Gentofte, DenmarkSteno Diabetes Center Copenhagen, Gentofte, DenmarkNovo Nordisk A/S, Måløv, DenmarkSteno Diabetes Center Copenhagen, Gentofte, DenmarkSteno Diabetes Center Copenhagen, Gentofte, DenmarkSteno Diabetes Center Copenhagen, Gentofte, DenmarkInstitute of Pharmaceutical Science, King's College London, London, United KingdomSteno Diabetes Center Copenhagen, Gentofte, DenmarkDepartment of Clinical Medicine, University of Copenhagen, Copenhagen, DenmarkBackground: Improved understanding of the pathophysiology causing diabetic kidney disease (DKD) is imperative. The aim of this study was to uncover associations between serum metabolites and renal outcomes.Methods: Non-targeted serum metabolomics analyses were performed in samples from 637 persons with type 1 diabetes using two-dimensional gas chromatography coupled to time-of-flight mass-spectrometry. Longitudinal data at follow-up (median 5.5 years) on renal events were obtained from national Danish health registries. A composite renal endpoint (n = 123) consisted of estimated glomerular filtration rate (eGFR) decline from baseline (≥30%), progression to end-stage renal disease and all-cause mortality. Metabolites with significant associations (p < 0.05) in any of the cross-sectional analyses with eGFR and albuminuria were analyzed for specific and composite endpoints. Adjustments included traditional cardiovascular risk factors and correction for multiple testing.Results: A data-driven partial correlation analysis revealed a dense fabric of co-regulated metabolites and clinical variables dominated by eGFR. Ribonic acid and myo-inositol were inversely associated with eGFR, positively associated with macroalbuminuria (p < 0.02) and longitudinally associated with higher risk of eGFR decline ≥30% (HR 2.2–2.7, CI [1.3–4.3], p < 0.001). Ribonic acid was associated with a combined renal endpoint (HR 1.8, CI [1.3–2.3], p = 0.001). The hydroxy butyrate 3,4-dihydroxybutanoic acid was cross-sectionally associated with micro- and macroalbuminuria, urinary albumin excretion rate and inversely associated with eGFR (p < 0.04) while branched chain amino acids were associated with eGFR and lower risk of the combined renal endpoint (p < 0.02).Conclusions: Alterations in serum metabolites, particularly polyols and amino acids, were associated with renal endpoints in type 1 diabetes highlighting molecular pathways associated with progression of kidney disease. External validation is needed to further assess their roles and potentials as future therapeutic targets.https://www.frontiersin.org/article/10.3389/fendo.2019.00818/fulldiabetic kidney diseasetype 1 diabetesmetabolomicsend-stage renal diseaseamino acidspolyols |
| spellingShingle | Nete Tofte Tommi Suvitaival Kajetan Trost Ismo Matias Mattila Simone Theilade Signe Abitz Winther Signe Abitz Winther Tarunveer Singh Ahluwalia Marie Frimodt-Møller Cristina Legido-Quigley Cristina Legido-Quigley Peter Rossing Peter Rossing Metabolomic Assessment Reveals Alteration in Polyols and Branched Chain Amino Acids Associated With Present and Future Renal Impairment in a Discovery Cohort of 637 Persons With Type 1 Diabetes Frontiers in Endocrinology diabetic kidney disease type 1 diabetes metabolomics end-stage renal disease amino acids polyols |
| title | Metabolomic Assessment Reveals Alteration in Polyols and Branched Chain Amino Acids Associated With Present and Future Renal Impairment in a Discovery Cohort of 637 Persons With Type 1 Diabetes |
| title_full | Metabolomic Assessment Reveals Alteration in Polyols and Branched Chain Amino Acids Associated With Present and Future Renal Impairment in a Discovery Cohort of 637 Persons With Type 1 Diabetes |
| title_fullStr | Metabolomic Assessment Reveals Alteration in Polyols and Branched Chain Amino Acids Associated With Present and Future Renal Impairment in a Discovery Cohort of 637 Persons With Type 1 Diabetes |
| title_full_unstemmed | Metabolomic Assessment Reveals Alteration in Polyols and Branched Chain Amino Acids Associated With Present and Future Renal Impairment in a Discovery Cohort of 637 Persons With Type 1 Diabetes |
| title_short | Metabolomic Assessment Reveals Alteration in Polyols and Branched Chain Amino Acids Associated With Present and Future Renal Impairment in a Discovery Cohort of 637 Persons With Type 1 Diabetes |
| title_sort | metabolomic assessment reveals alteration in polyols and branched chain amino acids associated with present and future renal impairment in a discovery cohort of 637 persons with type 1 diabetes |
| topic | diabetic kidney disease type 1 diabetes metabolomics end-stage renal disease amino acids polyols |
| url | https://www.frontiersin.org/article/10.3389/fendo.2019.00818/full |
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