2-Aminoadipic acid is a biomarker for diabetes risk.

J Clin Invest
Authors
Keywords
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.

Year of Publication
2013
Journal
J Clin Invest
Volume
123
Issue
10
Pages
4309-17
Date Published
2013 Oct
ISSN
1558-8238
URL
DOI
10.1172/JCI64801
PubMed ID
24091325
PubMed Central ID
PMC3784523
Links
Grant list
N01-HC-25195 / HC / NHLBI NIH HHS / United States
R01-DK-HL081572 / DK / NIDDK NIH HHS / United States
R01 HL081572 / HL / NHLBI NIH HHS / United States
Canadian Institutes of Health Research / Canada
N01HC25195 / HL / NHLBI NIH HHS / United States