ArticleThe Journal of clinical investigation2013
2-Aminoadipic acid is a biomarker for diabetes risk.
Article in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 259 papers, 4 of them syntheses that pooled it.
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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.
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Who cites it
259 citing papers in PubMed, 4 syntheses or guidelines pooled it, 461 citations in OpenAlex.
- Genetic Architecture of Plasma Alpha-Aminoadipic Acid Reveals a Relationship With High-Density Lipoprotein Cholesterol.Journal of the American Heart Association · 2022Pooled it
- Metabolomics and Type 2 Diabetes Risk: An Updated Systematic Review and Meta-analysis of Prospective Cohort Studies.Diabetes care · 2022Pooled it
- Associations of network-derived metabolite clusters with prevalent type 2 diabetes among adults of Puerto Rican descent.BMJ open diabetes research & care · 2021Pooled it
- Metabolomic profiling identifies complex lipid species and amino acid analogues associated with response to weight loss interventions.PloS one · 2021Pooled it
- Retatrutide and lipid and metabolite profiles in participants with obesity with or without type 2 diabetes.The Journal of clinical endocrinology and metabolism · 2026Trial
- Baseline gut microbiome and metabolome profiles predict weight loss after a structured lifestyle intervention.Microbiome · 2026Trial
- Hepatic steatosis in humans is associated with preserved glucagon action on amino acid metabolism.The Journal of clinical investigation · 2026Trial
- The consumption of animal products is associated with plasma levels of alpha-aminoadipic acid (2-AAA).Nutrition, metabolism, and cardiovascular diseases : NMCD · 2024Trial
- Workplace food purchases, dietary intake, and gut microbial metabolites in a secondary analysis of the ChooseWell 365 study.The American journal of clinical nutrition · 2024Trial
- Circulating Amino Acids and Risk of Peripheral Artery Disease in the PREDIMED Trial.International journal of molecular sciences · 2022Trial
- Divergent serum metabolomic, skeletal muscle signaling, transcriptomic, and performance adaptations to fasted versus whey protein-fed sprint interval training.American journal of physiology. Endocrinology and metabolism · 2021Trial
- Metabolomics of the tryptophan-kynurenine degradation pathway and risk of atrial fibrillation and heart failure: potential modification effect of Mediterranean diet.The American journal of clinical nutrition · 2021Trial
- Effect of Dapagliflozin on Urine Metabolome in Patients with Type 2 Diabetes.The Journal of clinical endocrinology and metabolism · 2021Trial
- Metabolites and diabetes remission after weight loss.Nutrition & diabetes · 2021Trial
- Use of Metabolomic Profiling to Understand Variability in Adiposity Changes Following an Intentional Weight Loss Intervention in Older Adults.Nutrients · 2020Trial
- Serum Argininosuccinic Acid Is Associated with Diabetes in Patients with Coronary Artery Disease: An Exploratory Targeted LC-MS/MS Study.International journal of molecular sciences · 2026Article
- Associations between serum amino acids and genetic liability to depression in the LURIC cohort.BMC psychiatry · 2026Article
- Coregulated metabolite networks associated with global protein crotonylation are central pathophysiological processes in prediabetes and diabetes.medRxiv : the preprint server for health sciences · 2026Article
- Multi-Organ Physiologic Deficits During Exercise Identify Clinical and Molecular Predisposition to Heart Failure with Preserved Ejection Fraction.Circulation · 2026Article
- The Response of Alpha-Aminoadipic Acid (2-AAA) to Short Term Lysine Ingestion in Healthy Individuals.Endocrinology, diabetes & metabolism · 2026Article
199 more citing papers are in PubMed but not listed here.
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Authors and funding
25 authors at 10 institutions in 4 countries.
Funding
Abstract
Improvements in metabolite-profiling techniques are providing increased breadth of coverage of the human metabolome and may highlight biomarkers and pathways in common diseases such as diabetes. Using a metabolomics platform that analyzes intermediary organic acids, purines, pyrimidines, and other compounds, we performed a nested case-control study of 188 individuals who developed diabetes and 188 propensity-matched controls from 2,422 normoglycemic participants followed for 12 years in the Framingham Heart Study. The metabolite 2-aminoadipic acid (2-AAA) was most strongly associated with the risk of developing diabetes. Individuals with 2-AAA concentrations in the top quartile had greater than a 4-fold risk of developing diabetes. Levels of 2-AAA were not well correlated with other metabolite biomarkers of diabetes, such as branched chain amino acids and aromatic amino acids, suggesting they report on a distinct pathophysiological pathway. In experimental studies, administration of 2-AAA lowered fasting plasma glucose levels in mice fed both standard chow and high-fat diets. Further, 2-AAA treatment enhanced insulin secretion from a pancreatic β cell line as well as murine and human islets. These data highlight a metabolite not previously associated with diabetes risk that is increased up to 12 years before the onset of overt disease. Our findings suggest that 2-AAA is a marker of diabetes risk and a potential modulator of glucose homeostasis in humans.
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What OpenQuestion 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 OpenQuestion graph.