Plasma Branched-Chain Amino Acids and Risk of Incident Type 2 Diabetes: Results from the PREVEND Prospective Cohort Study

Jose L. Flores-Guerrero*, Maryse C. J. Oste, Lyanne M. Kieneker, Eke G. Gruppen, Justyna Wolak-Dinsmore, James D. Otvos, Margery A. Connelly, Stephan J. L. Bakker, Robin P. F. Dullaart

*Corresponding author for this work

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Plasma branched-chain amino acids (BCAAs) are linked to metabolic disease, but their relevance for prediction of type 2 diabetes development is unclear. We determined the association of plasma BCAAs with type 2 diabetes risk in the prevention of renal and vascular end-stage disease (PREVEND) cohort. The BCAAs were measured by means of nuclear magnetic resonance spectroscopy. We evaluated the prospective associations of BCAAs with type 2 diabetes in 6244 subjects. The BCAAs were positively associated with HOMA-IR after multivariable adjustment (p <0.0001). During median follow-up for 7.5 years, 301 cases of type 2 diabetes were ascertained. The Kaplan-Meier plot demonstrated that patients in the highest BCAA quartile presented a higher risk (p log-rank <0.001). Cox regression analyses revealed a positive association between BCAA and type 2 diabetes; the hazard ratio (HR) for the highest quartile was 6.15 (95% CI: 4.08, 9.24, p <0.0001). After adjustment for multiple clinical and laboratory variables, the association remained (HR 2.80 (95% CI: 1.72, 4.53), p <0.0001). C-statistics, Net reclassification improvement, and -2 log likelihood were better after adding BCAAs to the traditional risk model (p = 0.01 to

Original languageEnglish
Article number513
Number of pages13
JournalJournal of Clinical Medicine
Issue number12
Publication statusPublished - Dec-2018


  • branched-chain amino acids
  • risk factor
  • type 2 diabetes
  • insulin resistance

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