Circulating metabolomic markers linking diabetic kidney disease and incident cardiovascular disease in type 2 diabetes : analyses from the Hong Kong Diabetes Biobank
© 2024. The Author(s)..
AIMS/HYPOTHESIS: The aim of this study was to describe the metabolome in diabetic kidney disease (DKD) and its association with incident CVD in type 2 diabetes, and identify prognostic biomarkers.
METHODS: From a prospective cohort of individuals with type 2 diabetes, baseline sera (N=1991) were quantified for 170 metabolites using NMR spectroscopy with median 5.2 years of follow-up. Associations of chronic kidney disease (CKD, eGFR<60 ml/min per 1.73 m2) or severely increased albuminuria with each metabolite were examined using linear regression, adjusted for confounders and multiplicity. Associations between DKD (CKD or severely increased albuminuria)-related metabolites and incident CVD were examined using Cox regressions. Metabolomic biomarkers were identified and assessed for CVD prediction and replicated in two independent cohorts.
RESULTS: At false discovery rate (FDR)<0.05, 156 metabolites were associated with DKD (151 for CKD and 128 for severely increased albuminuria), including apolipoprotein B-containing lipoproteins, HDL, fatty acids, phenylalanine, tyrosine, albumin and glycoprotein acetyls. Over 5.2 years of follow-up, 75 metabolites were associated with incident CVD at FDR<0.05. A model comprising age, sex and three metabolites (albumin, triglycerides in large HDL and phospholipids in small LDL) performed comparably to conventional risk factors (C statistic 0.765 vs 0.762, p=0.893) and adding the three metabolites further improved CVD prediction (C statistic from 0.762 to 0.797, p=0.014) and improved discrimination and reclassification. The 3-metabolite score was validated in independent Chinese and Dutch cohorts.
CONCLUSIONS/INTERPRETATION: Altered metabolomic signatures in DKD are associated with incident CVD and improve CVD risk stratification.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:67 |
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| Enthalten in: |
Diabetologia - 67(2024), 5 vom: 25. März, Seite 837-849 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Jin, Qiao [VerfasserIn] |
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| Links: |
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| Themen: |
Albumins |
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| Anmerkungen: |
Date Completed 21.03.2024 Date Revised 23.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s00125-024-06108-5 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Jin, Qiao |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Circulating metabolomic markers linking diabetic kidney disease and incident cardiovascular disease in type 2 diabetes |b analyses from the Hong Kong Diabetes Biobank |
| 264 | 1 | |c 2024 | |
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| 500 | |a Date Completed 21.03.2024 | ||
| 500 | |a Date Revised 23.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024. The Author(s). | ||
| 520 | |a AIMS/HYPOTHESIS: The aim of this study was to describe the metabolome in diabetic kidney disease (DKD) and its association with incident CVD in type 2 diabetes, and identify prognostic biomarkers | ||
| 520 | |a METHODS: From a prospective cohort of individuals with type 2 diabetes, baseline sera (N=1991) were quantified for 170 metabolites using NMR spectroscopy with median 5.2 years of follow-up. Associations of chronic kidney disease (CKD, eGFR<60 ml/min per 1.73 m2) or severely increased albuminuria with each metabolite were examined using linear regression, adjusted for confounders and multiplicity. Associations between DKD (CKD or severely increased albuminuria)-related metabolites and incident CVD were examined using Cox regressions. Metabolomic biomarkers were identified and assessed for CVD prediction and replicated in two independent cohorts | ||
| 520 | |a RESULTS: At false discovery rate (FDR)<0.05, 156 metabolites were associated with DKD (151 for CKD and 128 for severely increased albuminuria), including apolipoprotein B-containing lipoproteins, HDL, fatty acids, phenylalanine, tyrosine, albumin and glycoprotein acetyls. Over 5.2 years of follow-up, 75 metabolites were associated with incident CVD at FDR<0.05. A model comprising age, sex and three metabolites (albumin, triglycerides in large HDL and phospholipids in small LDL) performed comparably to conventional risk factors (C statistic 0.765 vs 0.762, p=0.893) and adding the three metabolites further improved CVD prediction (C statistic from 0.762 to 0.797, p=0.014) and improved discrimination and reclassification. The 3-metabolite score was validated in independent Chinese and Dutch cohorts | ||
| 520 | |a CONCLUSIONS/INTERPRETATION: Altered metabolomic signatures in DKD are associated with incident CVD and improve CVD risk stratification | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Cardiovascular disease | |
| 650 | 4 | |a Diabetic kidney disease | |
| 650 | 4 | |a Metabolomics | |
| 650 | 4 | |a NMR spectroscopy | |
| 650 | 4 | |a Prognostic biomarker | |
| 650 | 4 | |a Risk stratification | |
| 650 | 4 | |a Severely increased albuminuria | |
| 650 | 4 | |a Type 2 diabetes | |
| 650 | 7 | |a Biomarkers |2 NLM | |
| 650 | 7 | |a Albumins |2 NLM | |
| 700 | 1 | |a Lau, Eric S H |e verfasserin |4 aut | |
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| 700 | 1 | |a Tam, Claudia H T |e verfasserin |4 aut | |
| 700 | 1 | |a Ozaki, Risa |e verfasserin |4 aut | |
| 700 | 1 | |a Lim, Cadmon K P |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Hongjiang |e verfasserin |4 aut | |
| 700 | 1 | |a Chow, Elaine Y K |e verfasserin |4 aut | |
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| 700 | 1 | |a Lee, Heung Man |e verfasserin |4 aut | |
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| 700 | 1 | |a Jiang, Guozhi |e verfasserin |4 aut | |
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| 700 | 1 | |a Fung, Samuel |e verfasserin |4 aut | |
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| 700 | 1 | |a Yu, Weichuan |e verfasserin |4 aut | |
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| 700 | 1 | |a Tomlinson, Brian |e verfasserin |4 aut | |
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| 700 | 1 | |a Lan, Hui-Yao |e verfasserin |4 aut | |
| 700 | 1 | |a Szeto, Cheuk Chun |e verfasserin |4 aut | |
| 700 | 1 | |a So, Wing Yee |e verfasserin |4 aut | |
| 700 | 1 | |a Jenkins, Alicia J |e verfasserin |4 aut | |
| 700 | 1 | |a Fung, Erik |e verfasserin |4 aut | |
| 700 | 1 | |a Muilwijk, Mirthe |e verfasserin |4 aut | |
| 700 | 1 | |a Blom, Marieke T |e verfasserin |4 aut | |
| 700 | 1 | |a 't Hart, Leen M |e verfasserin |4 aut | |
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