Ottosson F, et al. - Working with the theory that alterations in metabolism happen years before clinical manifestation of type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) and are reflected in the plasma metabolome, researchers investigated plasma metabolites that forecast future T2DM and CAD. Findings revealed several plasma metabolites correlate with incidence of T2DM and CAD. Elevated glutamate and reduced asparagine levels were linked to both diseases. These associations might help to understand reasons for the common coincidence of T2DM and CAD.

Methods

• In 1,049 individuals (drawn from a population sample of 5,386 in the Malmö Preventive Project [mean age, 69.5 years; 31% women]) without CAD and diabetes, researchers quantified 35 plasma metabolites (amino acid metabolites and acylcarnitines) using targeted liquid chromatography-mass spectrometry.

Results

• During a mean follow-up of 6.1 years, 204 individuals developed T2DM, 384 developed CAD, and 496 remained T2DM and CAD free.
• Logistic regression models yielded 16 metabolites that were significantly associated with risk for developing T2DM.
• The most strongly associated metabolite was glutamate (OR, 1.96; P=5.4e-12), followed by increased levels of branched-chain amino acids.
• Three metabolites were predictors for incident CAD: glutamate (OR, 1.28; P=6.6e-4), histidine (OR, 0.76; P=5.1e-4), and asparagine (OR, 0.80; P=2.2e-3).
• They noted glutamate (OR, 1.48; P=1.6e-8) and asparagine (OR, 0.75; P=1.8e-5) were associated with a composite endpoint of developing T2DM or CAD.