13-OR: Effects of Randomized Statin Therapy vs. Placebo on Plasma Branched-Chain Amino Acids (BCAAs) and Type 2 Diabetes (T2D) Risk: Secondary Analysis of the JUPITER Trial

Abstract

Background: Statins increase T2D risk despite favorable effects on lipids, inflammation, and cardiovascular disease (CVD). Statins may modulate associations of T2D-related BCAAs with incident T2D. Methods: JUPITER (NCT00239681) randomized rosuvastatin vs. placebo for primary CVD prevention. Plasma BCAAs (isoleucine, leucine, valine) and alanine were quantified via NMR spectroscopy for n=12,441 at baseline and n=9,826 with repeat 12mo samples. We calculated % change in metabolites with mixed effects linear regression. We used Cox models to evaluate baseline and change (per SD) of metabolites with incident T2D (multivariable-adj HR [95%CI]) during 2y of follow-up (max. 5y). Results: Overall, statin vs. placebo increased T2D (HR 1.25 [95% CI: 1.05-1.49]). BCAA metabolites changed modestly at 12mo; only leucine differed with statin vs. placebo (+3.7% vs. +2.4%; p=0.03). Baseline BCAAs were associated with T2D. Each SD increase in isoleucine, leucine, valine, and alanine was associated with HR=1.3 (1.1-1.5), 1.1 (1.0, 1.3), 1.3 (1.1, 1.5), and 1.3 (1.1, 1.5) greater T2D risk (FIGURE). Associations did not differ with statin vs. placebo. Conclusion: High-intensity statin therapy had at most modest effects on BCAA metabolites. Baseline and change in BCAAs and alanine were associated with T2D, including during randomized statin therapy. Disclosure D. K. Tobias: None. P. Ridker: Consultant; Self; 360 Marketing Strategic Services, AstraZeneca, Corvidia Therapeutics, CSL Behring, DalCor Pharmaceuticals, Novartis AG, Omeicos, Flame, Uppton, Agepha, sIRNAomics, Research Support; Self; Amarin Corporation plc, Kowa Pharmaceuticals America, Inc., Novo Nordisk. R. Glynn: Research Support; Self; AstraZeneca, Kowa Research Institute, Inc., Novartis AG, Pfizer Inc. S. Mora: Consultant; Self; Pfizer Inc., Quest Diagnostics, Other Relationship; Self; LabCorp. Funding American Diabetes Association (1-19-JDF-115 to D.K.T.); Brigham and Women’s Hospital (to D.K.T.); National Institutes of Health (R01HL117861, R01HL134811, K24HL136852, R01DK112940 to S.M.); LabCorp