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A Novel Biomarker for Determining Diabetes Risk

2-AAA has been correlated with future development of diabetes…. 

Researchers from the Cardiovascular Research Center have published results regarding new metabolic biomarkers that indicate increased diabetes risk. By taking advantage of advancing technology for metabolite profiling using liquid chromatography-mass spectrometry, the researchers were able to identify high levels of a metabolite biomarker called 2-aminoadipic acid (2-AAA) in the blood which indicates a four-fold increased risk for developing diabetes in the future. The results still held after adjusting for other factors that can contribute to insulin resistance. The results of the study are backed up by the fact it is from 2 large, independent, epidemiological cohorts with over ten years of follow-up. The study was performed in normoglycemic individuals.

2-AAA is formed as a result of lysine degradation. 2-AAA was shown, in vivo, to moderate glucose homeostasis in follow-up experiments. In vitro, studies show that 2-AAA can affect insulin secretion in pancreatic beta-cells and isolated islets. In the future, testing for this metabolite can determine whether or not a person is at risk for future development of diabetes. It also means that more research into 2-AAA, its pathways, and its precise involvement in glucose homeostasis, insulin secretion, and diabetes development, is warranted.

Practice Pearls:

  • 2-AAA is a metabolic breakdown product of lysine that was shown to have in vitro and in vivo effects on insulin secretion and glucose homeostasis.
  • Using case-control cohorts (Framingham Heart Study, Mälmo Diet and Cancer Study), high plasma levels of 2-AAA were shown to increase future diabetes risk by a factor of 4 in normoglycemic individuals.
  • Future applicability of this metabolite include preventative care testing as well as therapeutic options following randomized trials.

Journal of Clinical Investigation, October 2013