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2-Aminoadipic acid is a biomarker for diabetes risk

Wang, Thomas J. ; Ngo, Debby ; Psychogios, Nikolaos ; Dejam, Andre ; Larson, Martin G. ; Vasan, Ramachandran S. ; Ghorbani, Anahita ; O'Sullivan, John ; Cheng, Susan and Rhee, Eugene P. , et al. (2013) In Journal of Clinical Investigation 123(10). p.4309-4317
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... (More)
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 beta 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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Clinical Investigation
volume
123
issue
10
pages
4309 - 4317
publisher
The American Society for Clinical Investigation
external identifiers
  • wos:000325443100026
  • scopus:84885031125
  • pmid:24091325
ISSN
0021-9738
DOI
10.1172/JCI64801
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Hypertension and Cardiovascular Disease (013242540), Emergency medicine/Medicine/Surgery (013240200)
id
5c6f4e38-1f83-4892-a4e0-357e0aac1eff (old id 4163444)
date added to LUP
2016-04-01 12:57:03
date last changed
2024-01-09 04:17:01
@article{5c6f4e38-1f83-4892-a4e0-357e0aac1eff,
  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 beta 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.}},
  author       = {{Wang, Thomas J. and Ngo, Debby and Psychogios, Nikolaos and Dejam, Andre and Larson, Martin G. and Vasan, Ramachandran S. and Ghorbani, Anahita and O'Sullivan, John and Cheng, Susan and Rhee, Eugene P. and Sinha, Sumita and McCabe, Elizabeth and Fox, Caroline S. and O'Donnell, Christopher J. and Ho, Jennifer E. and Florez, Jose C. and Magnusson, Martin and Pierce, Kerry A. and Souza, Amanda L. and Yu, Yi and Carter, Christian and Light, Peter E. and Melander, Olle and Clish, Clary B. and Gerszten, Robert E.}},
  issn         = {{0021-9738}},
  language     = {{eng}},
  number       = {{10}},
  pages        = {{4309--4317}},
  publisher    = {{The American Society for Clinical Investigation}},
  series       = {{Journal of Clinical Investigation}},
  title        = {{2-Aminoadipic acid is a biomarker for diabetes risk}},
  url          = {{https://lup.lub.lu.se/search/files/3064629/4587261.pdf}},
  doi          = {{10.1172/JCI64801}},
  volume       = {{123}},
  year         = {{2013}},
}