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Olle Melander

Principal investigator

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2-Aminoadipic acid is a biomarker for diabetes risk

Author

  • Thomas J. Wang
  • Debby Ngo
  • Nikolaos Psychogios
  • Andre Dejam
  • Martin G. Larson
  • Ramachandran S. Vasan
  • Anahita Ghorbani
  • John O'Sullivan
  • Susan Cheng
  • Eugene P. Rhee
  • Sumita Sinha
  • Elizabeth McCabe
  • Caroline S. Fox
  • Christopher J. O'Donnell
  • Jennifer E. Ho
  • Jose C. Florez
  • Martin Magnusson
  • Kerry A. Pierce
  • Amanda L. Souza
  • Yi Yu
  • Christian Carter
  • Peter E. Light
  • Olle Melander
  • Clary B. Clish
  • Robert E. Gerszten

Summary, in English

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.

Department/s

  • Cardiovascular Research - Hypertension
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health

Publishing year

2013

Language

English

Pages

4309-4317

Publication/Series

Journal of Clinical Investigation

Volume

123

Issue

10

Document type

Journal article

Publisher

Am Soc Clin Investig

Topic

  • Clinical Medicine
  • Cardiac and Cardiovascular Systems

Status

Published

Research group

  • Cardiovascular Research - Hypertension

ISBN/ISSN/Other

  • ISSN: 0021-9738