Metabolomic Study Reveals Early Diagnostic Marker for Type II Diabetes

The metabolite 2-aminoadipic acid (2-AAA) has been identified as a biomarker that can predict risk of developing type II diabetes up to 10 years before onset of the disease.

Investigators at Vanderbilt University (Nashville, TN, USA) and their colleagues at Harvard Medical School (Boston, MA, USA) employed a liquid chromatography–tandem mass spectrometry (LC-MS/MS) metabolomics platform that analyzed intermediary organic acids, purines, pyrimidines, and other compounds. Metabolomics is the study of chemical processes involving metabolites, while the metabolome represents the collection of all metabolites in a biological cell, tissue, organ, or organism that are the end products of cellular processes.

For this study, the investigators performed a nested case-control study of 188 individuals who developed type II diabetes and 188 matched controls from a group of 2,422 nondiabetic participants followed for 12 years in the Framingham Heart Study.

Results revealed that 2-AAA was the metabolite most strongly associated with the risk of developing type II diabetes. Individuals with 2-AAA concentrations in the top quartile had greater than a four-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 physiological pathway.

In experimental studies, administration of 2-AAA lowered fasting plasma glucose levels in mice fed both standard chow and high-fat diets. Furthermore, 2-AAA treatment enhanced insulin secretion from a pancreatic beta-cell line as well as murine and human islets.

“From the baseline blood samples, we identified a novel biomarker, 2-aminoadipic acid (2-AAA) that was higher in people who went on to develop diabetes than in those who did not,” said first author Dr. Thomas J. Wang, professor of cardiology at Vanderbilt University. “That information was above and beyond knowing their blood sugar at baseline, knowing whether they were obese, or had other characteristics that put them at risk. 2-AAA appears to be more than a passive marker. It actually seems to play a role in glucose metabolism. It is still a bit early to understand the biological implications of that role, but these experimental data are intriguing in that this molecule could be contributing in some manner to the development of the disease itself.”

“Diabetes is common and the prevalence will only rise in coming years fueled by the rise of obesity. Understanding why diabetes occurs and how it might be prevented is a very intense area of investigation because of the serious consequences of having the disease,” said Dr. Wang. “It is certainly a focus of many research groups to understand how we might develop strategies to detect diabetes risk at an earlier stage and intervene.”

The study was published in the September 16, 2013, online edition of the Journal of Clinical Investigation.

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Vanderbilt University
Harvard Medical School