ArticleScientific reports2021
Triangulating evidence from longitudinal and Mendelian randomization studies of metabolomic biomarkers for type 2 diabetes.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 2 of them syntheses that pooled it.
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Who cites it
23 citing papers in PubMed, 2 syntheses or guidelines pooled it, 35 citations in OpenAlex.
- Genetic loci of beta-aminoisobutyric acid are associated with aging-related mild cognitive impairment.Translational psychiatry · 2023Pooled it
- The Metabolic Signature of Cardiorespiratory Fitness: A Systematic Review.Sports medicine (Auckland, N.Z.) · 2022Pooled it
- Unravelling the molecular mechanisms causal to type 2 diabetes across global populations and disease-relevant tissues.Nature metabolism · 2026Article
- Longitudinal omics data analysis: approaches and applications.Computational and structural biotechnology journal · 2026Review
- Study Protocol for HeartMagic: A Prospective Observational Cohort Characterizing Subtypes of Heart Failure With Preserved Ejection Fraction.Journal of the American Heart Association · 2025Article
- Association of circulating metabolites and polygenic risk score with incident type 2 diabetes: a prospective community-based cohort study.Cardiovascular diabetology · 2025Article
- Circulating miR-4454 as a potential biomarker for the diagnosis of T2DM and the prediction value of comorbidity and complications in T2DM.BMC endocrine disorders · 2025Article
- Coronary heart disease and type 2 diabetes metabolomic signatures in the Middle East.Frontiers in endocrinology · 2025Article
- Disentangling the consequences of type 2 diabetes on targeted metabolite profiles using causal inference and interaction QTL analyses.PLoS genetics · 2024Article
- Analysis of metabolites associated with ADIPOQ genotypes in individuals with type 2 diabetes mellitus.Scientific reports · 2024Article
- Choline Metabolites and 15-Year Risk of Incident Diabetes in a Prospective Cohort of Adults: Coronary Artery Risk Development in Young Adults (CARDIA) Study.Diabetes care · 2024Article
- Causal inference in health and disease: a review of the principles and applications of Mendelian randomization.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2024Review
- The metabolic signature of blood lipids: a causal inference study using twins.Journal of lipid research · 2024Article
- Branched-Chain and Aromatic Amino Acids, Type 2 Diabetes, and Cardiometabolic Risk Factors among Puerto Rican Adults.Nutrients · 2024Article
- The association between body mass index and metabolite response to a liquid mixed meal challenge: a Mendelian randomization study.The American journal of clinical nutrition · 2024Article
- Inter-organ crosstalk during development and progression of type 2 diabetes mellitus.Nature reviews. Endocrinology · 2024Review
- Metabolomic epidemiology offers insights into disease aetiology.Nature metabolism · 2023Review
- Causal factors underlying diabetes risk informed by Mendelian randomisation analysis: evidence, opportunities and challenges.Diabetologia · 2023Review
- Exploiting the mediating role of the metabolome to unravel transcript-to-phenotype associations.eLife · 2023Article
- Several Metabolite Families Display Inflexibility during Glucose Challenge in Patients with Type 2 Diabetes: An Untargeted Metabolomics Study.Metabolites · 2023Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The number of people affected by Type 2 diabetes mellitus (T2DM) is close to half a billion and is on a sharp rise, representing a major and growing public health burden. Given its mild initial symptoms, T2DM is often diagnosed several years after its onset, leaving half of diabetic individuals undiagnosed. While several classical clinical and genetic biomarkers have been identified, improving early diagnosis by exploring other kinds of omics data remains crucial. In this study, we have combined longitudinal data from two population-based cohorts CoLaus and DESIR (comprising in total 493 incident cases vs. 1360 controls) to identify new or confirm previously implicated metabolomic biomarkers predicting T2DM incidence more than 5 years ahead of clinical diagnosis. Our longitudinal data have shown robust evidence for valine, leucine, carnitine and glutamic acid being predictive of future conversion to T2DM. We confirmed the causality of such association for leucine by 2-sample Mendelian randomisation (MR) based on independent data. Our MR approach further identified new metabolites potentially playing a causal role on T2D, including betaine, lysine and mannose. Interestingly, for valine and leucine a strong reverse causal effect was detected, indicating that the genetic predisposition to T2DM may trigger early changes of these metabolites, which appear well-before any clinical symptoms. In addition, our study revealed a reverse causal effect of metabolites such as glutamic acid and alanine. Collectively, these findings indicate that molecular traits linked to the genetic basis of T2DM may be particularly promising early biomarkers.
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