| Title: | Plasma metabolomics identifies key metabolites and improves prediction of diabetic retinopathy: development and validation across multi-national cohorts |
| Journal: | Ophthalmology |
| Published: | 5 Jul 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38972358/ |
| DOI: | https://doi.org/10.1016/j.ophtha.2024.07.004 |
Publication 11703
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Abstract
PURPOSE: To identify longitudinal metabolomic fingerprints of diabetic retinopathy (DR) and evaluate their utility in predicting DR development and progression.</p>
DESIGN: Multicenter, multi-ethnic cohort study.</p>
PARTICIPANTS: This study included 17,675 participants with baseline pre-diabetes/diabetes, in accordance with the 2021 American Diabetes Association guideline, and free of baseline DR from the UK Biobank (UKB); and an additional 638 diabetic participants from the Guangzhou Diabetic Eye Study (GDES) for external validation.</p>
METHODS: Longitudinal DR metabolomic fingerprints were identified through nuclear magnetic resonance assay in UKB participants. The predictive value of these fingerprints for predicting DR development were assessed in a fully withheld test set. External validation and extrapolation analyses of DR progression and microvascular damage were conducted in the GDES cohort. Model assessments included the C-statistic, net classification improvement (NRI), integrated discrimination improvement (IDI), calibration, and clinical utility in both cohorts.</p>
MAIN OUTCOME MEASURES: DR development, progression, and retinal microvascular damage.</p>
RESULTS: Of 168 metabolites, 118 were identified as candidate metabolomic fingerprints for future DR development. These fingerprints significantly improved the predictability for DR development beyond traditional indicators (C-statistic: 0.802, 95% CI, 0.760-0.843 vs. 0.751, 95% CI, 0.706-0.796; P = 5.56×10-4). Glucose, lactate, and citrate were among the fingerprints validated in the GDES cohort. Using these parsimonious and replicable fingerprints yielded similar improvements for predicting DR development (C-statistic: 0.807, 95% CI, 0.711-0.903 vs. 0.617, 95% CI, 0.494, 0.740; P = 1.68×10-4) and progression (C-statistic: 0.797, 95% CI, 0.712-0.882 vs. 0.665, 95% CI, 0.545-0.784; P = 0.003) in the external cohort. Improvements in NRIs, IDIs, and clinical utility were also evident in both cohorts (all P <0.05). In addition, lactate and citrate were associated to microvascular damage across macular and optic disc regions (all P <0.05).</p>
CONCLUSIONS: Metabolomic profiling has proven effective in identifying robust fingerprints for predicting future DR development and progression, providing novel insights into the early and advanced stages of DR pathophysiology.</p>
14 Keywords
- Adult
- Aged
- Biomarkers
- Diabetes Mellitus, Type 2
- Diabetic Retinopathy
- Disease Progression
- Female
- Humans
- Male
- Metabolome
- Metabolomics
- Middle Aged
- Predictive Value of Tests
- United Kingdom
12 Authors
- Shaopeng Yang
- Riqian Liu
- Zhuoyao Xin
- Ziyu Zhu
- Jiaqing Chu
- Pingting Zhong
- Lisa Zhuoting Zhu
- Xianwen Shang
- Wenyong Huang
- Lei Zhang
- Mingguang He
- Wei Wang
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