ArticleDiabetes care2022
Serum Orotidine: A Novel Biomarker of Increased CVD Risk in Type 2 Diabetes Discovered Through Metabolomics Studies.
Article in Diabetes care, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 11 citations in OpenAlex.
- Acylcarnitines and prediction of renal function decline in type 2 diabetes.BMJ open diabetes research & care · 2026Article
- Exploring the Causal Relationship Between Blood Metabolites and Chronic Periodontitis: Insights From Genetic Causal Analysis.Journal of cellular and molecular medicine · 2025Article
- Detecting a potential causal relationship between plasma metabolites and myocardial infarction using bidirectional and two-step Mendelian randomization.Scientific reports · 2025Article
- Low-frequency variants in genes involved in glutamic acid metabolism and γ-glutamyl cycle and risk of coronary artery disease in type 2 diabetes.Cardiovascular diabetology · 2024Article
- Circulating Metabolite Profiles and Risk of Coronary Heart Disease Among Racially and Geographically Diverse Populations.Circulation. Genomic and precision medicine · 2024Article
- Metabolomic profiles during early childhood and risk of food allergies and asthma in multiethnic children from a prospective birth cohort.The Journal of allergy and clinical immunology · 2024Article
- Exploring the design of clinical research studies on the efficacy mechanisms in type 2 diabetes mellitus.Frontiers in endocrinology · 2024Review
- Review
- Untargeted metabolomics analysis on kidney tissues from mice reveals potential hypoxia biomarkers.Scientific reports · 2023Article
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Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
Abstract
objectiveTo identify novel biomarkers of cardiovascular disease (CVD) risk in type 2 diabetes (T2D) via a hypothesis-free global metabolomics study, while taking into account renal function, an important confounder often overlooked in previous metabolomics studies of CVD. RESEARCH DESIGN AND
methodsWe conducted a global serum metabolomics analysis using the Metabolon platform in a discovery set from the Joslin Kidney Study having a nested case-control design comprising 409 individuals with T2D. Logistic regression was applied to evaluate the association between incident CVD events and each of the 671 metabolites detected by the Metabolon platform, before and after adjustment for renal function and other CVD risk factors. Significant metabolites were followed up with absolute quantification assays in a validation set from the Joslin Heart Study including 599 individuals with T2D with and without clinical evidence of significant coronary heart disease (CHD).
resultsIn the discovery set, serum orotidine and 2-piperidinone were significantly associated with increased odds of incident CVD after adjustment for glomerular filtration rate (GFR) (odds ratio [OR] per SD increment 1.94 [95% CI 1.39-2.72], P = 0.0001, and 1.62 [1.26-2.08], P = 0.0001, respectively). Orotidine was also associated with increased odds of CHD in the validation set (OR 1.39 [1.11-1.75]), while 2-piperidinone did not replicate. Furthermore, orotidine, being inversely associated with GFR, mediated 60% of the effects of declining renal function on CVD risk. Addition of orotidine to established clinical predictors improved (P < 0.05) C statistics and discrimination indices for CVD risk (ΔAUC 0.053, rIDI 0.48, NRI 0.42) compared with the clinical predictors alone.
conclusionsThrough a robust metabolomics approach, with independent validation, we have discovered serum orotidine as a novel biomarker of increased odds of CVD in T2D, independent of renal function. Additionally, orotidine may be a biological mediator of the increased CVD risk associated with poor kidney function and may help improve CVD risk prediction in T2D.
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