Abstract 11088: Pharmacometabolomics Reveals a Novel Signature for Predicting Beta Blocker Associated Impaired Fasting Glucose
BACKGROUND We investigated whether a metabolomic profile of amino acids, previously associated with incident diabetes, could predict incident impaired fasting glucose (IFG) after exposure to atenolol, a beta blocker with known adverse metabolic effects.
METHODS Among 229 normoglycemic patients enrolled in the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study and treated with atenolol for 9 weeks, 35 (15%) developed IFG (cases). Controls were normoglycemic at enrollment, treated with atenolol and did not develop IFG. Metabolomic profiles were determined for cases and controls using a GCTOF platform. We assessed the impact of baseline abundance of three branched-chain (BCAA) (isoleucine, Ile, leucine, Leu and valine, Val) and two aromatic (AAA) (tyrosine, Try and phenylalanine, Phe) amino acids (AA), on incidence of IFG.
RESULTS Change in glucose after treatment with atenolol was significantly higher in cases than controls in whites (median 12.0 mg/dl vs. 2.8mg/dl, p<0.001) and blacks (median 23 mg/dl vs. 1.5 mg/dl, p<0.001). In whites, the BCAA Ile (r=0.26, p=0.004), Leu (r=0.23, p=0.009) and Val (r-0.19, p=0.038) were significantly correlated with change in glucose, and all AAs were strongly associated with development of IFG. Each increment in standard deviation of the five AA abundance was associated with a 62-98% increased odds of developing IFG after adjustment for fasting glucose, insulin and HOMA-IR, (p=0.007-0.0004) (Figure). In blacks, we did not observe any significant correlations or associations with any AA, despite similar AA abundance among whites and blacks and cases and controls.
CONCLUSION Our data provide important insight into the mechanisms underlying atenolol associated adverse metabolic effects. Importantly, our results suggest BCAA and AAA are similarly associated with drug-induced IFG and diabetes development in whites, and AA profiling may be a valuable tool to screen for risk of drug-induced dysglycemia.
- © 2012 by American Heart Association, Inc.