SynthesisJCI insight2023
Mitochondrial metabolites predict adverse cardiovascular events in individuals with diabetes.
Synthesis in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 13 citations in OpenAlex.
- Metabolic inflexibility across heart failure phenotypes: mechanisms and type-specific therapeutic implications.Apoptosis : an international journal on programmed cell death · 2026Review
- Biomarkers of Cardiac Metabolic Flexibility in Health, HFrEF and HFpEF.International journal of molecular sciences · 2026Review
- AI-driven identification of nutrition-modulated biomarkers and drug targets for cardiovascular therapeutic mechanisms.Frontiers in pharmacology · 2026Review
- Clinical perspectives of new insights and tools to minimize the hypoglycaemia burden connected with type 2 diabetes pharmacotherapy.Cardiovascular diabetology · 2025Article
- Article
- Mitochondrial Transport Proteins in Cardiovascular Diseases: Metabolic Gatekeepers, Pathogenic Mediators and Therapeutic Targets.International journal of molecular sciences · 2025Review
- Mitochondrial Dysfunction in the Development and Progression of Cardiometabolic Diseases: A Narrative Review.Journal of clinical medicine · 2025Review
- Obesity and acylcarnitine derivates interplay with coronary artery disease.Scientific reports · 2025Article
- CVOT summit report 2024: new cardiovascular, kidney, and metabolic outcomes.Cardiovascular diabetology · 2025Article
- Review
- Risk prediction of cardiovascular events in peritoneal dialysis patients.BMC nephrology · 2025Article
- Smoking-related gut microbiota alteration is associated with obesity and obesity-related diseases: results from two cohorts with sibling comparison analyses.BMC medicine · 2025Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 9 institutions in 6 countries.
Funding
Abstract
Metabolic mechanisms underlying the heterogeneity of major adverse cardiovascular (CV) event (MACE) risk in individuals with type 2 diabetes mellitus (T2D) remain unclear. We hypothesized that circulating metabolites reflecting mitochondrial dysfunction predict incident MACE in T2D. Targeted mass-spectrometry profiling of 60 metabolites was performed on baseline plasma samples from the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS; discovery cohort) and Exenatide Study of Cardiovascular Event Lowering (EXSCEL; validation cohort) biomarker substudy cohorts. A principal components analysis metabolite factor comprising medium-chain acylcarnitines (MCACs) was associated with MACE in TECOS and validated in EXSCEL, with higher levels associated with higher MACE risk. Meta-analysis showed that long-chain acylcarnitines (LCACs) and dicarboxylacylcarnitines were also associated with MACE. Metabolites remained associated with MACE in multivariate models and favorably changed with exenatide therapy. A third cohort (Cardiac Catheterization Genetics [CATHGEN]) with T2D was assessed to determine whether these metabolites improved discriminative capability of multivariate models for MACE. Nine metabolites (MCACs and LCACs and 1 dicarboxylacylcarnitine) were associated with time to MACE in the CATHGEN cohort. Addition of these metabolites to clinical models minimally improved the discriminative capability for MACE but did significantly down reclassify risk. Thus, metabolites reporting on dysregulated mitochondrial fatty acid oxidation are present in higher levels in individuals with T2D who experience subsequent MACE. These biomarkers may improve CV risk prediction models, be therapy responsive, and highlight emerging risk mechanisms.
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What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.