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Open AccessArticle

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

1
Department of Internal Medicine, UMCG, University of Groningen, 9713 GZ Groningen, The Netherlands
2
Department of Endocrinology, UMCG, University of Groningen, 9713 GZ Groningen, The Netherlands
3
Laboratory Corporation of America Holdings (LabCorp), Morrisville, NC 27560, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
J. Clin. Med. 2018, 7(12), 513; https://doi.org/10.3390/jcm7120513
Received: 9 November 2018 / Revised: 21 November 2018 / Accepted: 27 November 2018 / Published: 4 December 2018
(This article belongs to the Special Issue Type 2 Diabetes: Update on Pathophysiology and Treatment)
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 <0.001). In conclusions, high concentrations of BCAAs associate with insulin resistance and with increased risk of type 2 diabetes. This association is independent of multiple risk factors, HOMA-IR and β cell function. View Full-Text
Keywords: branched-chain amino acids; risk factor; type 2 diabetes; insulin resistance branched-chain amino acids; risk factor; type 2 diabetes; insulin resistance
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Flores-Guerrero, J.L.; Osté, M.C.J.; Kieneker, L.M.; Gruppen, E.G.; Wolak-Dinsmore, J.; Otvos, J.D.; Connelly, M.A.; Bakker, S.J.L.; Dullaart, R.P.F. Plasma Branched-Chain Amino Acids and Risk of Incident Type 2 Diabetes: Results from the PREVEND Prospective Cohort Study. J. Clin. Med. 2018, 7, 513.

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