High Plasma Branched-Chain Amino Acids Are Associated with Higher Risk of Post-Transplant Diabetes Mellitus in Renal Transplant Recipients

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

*Corresponding author for this work

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Post-transplant diabetes mellitus (PTDM) is a serious complication in renal transplant recipients. Branched-chain amino acids (BCAAs) are involved in the pathogenesis of insulin resistance. We determined the association of plasma BCAAs with PTDM and included adult renal transplant recipients (>= 18 y) with a functioning graft for >= 1 year in this cross-sectional cohort study with prospective follow-up. Plasma BCAAs were measured in 518 subjects using nuclear magnetic resonance spectroscopy. We excluded subjects with a history of diabetes, leaving 368 non-diabetic renal transplant recipients eligible for analyses. Cox proportional hazards analyses were used to assess the association of BCAAs with the development of PTDM. Mean age was 51.1 +/- 13.6 y (53.6% men) and plasma BCAA was 377.6 +/- 82.5 mu M. During median follow-up of 5.3 (IQR, 4.2-6.0) y, 38 (9.8%) patients developed PTDM. BCAAs were associated with a higher risk of developing PTDM (HR: 1.43, 95% CI 1.08-1.89) per SD change (p = 0.01), independent of age and sex. Adjustment for other potential confounders did not significantly change this association, although adjustment for HbA1c eliminated it. The association was mediated to a considerable extent (53%) by HbA1c. The association was also modified by HbA1c; BCAAs were only associated with renal transplant recipients without prediabetes (HbA1c <5.7%). In conclusion, high concentrations of plasma BCAAs are associated with developing PTDM in renal transplant recipients. Alterations in BCAAs may represent an early predictive biomarker for PTDM.

Original languageEnglish
Article number511
Number of pages19
JournalJournal of Clinical Medicine
Issue number2
Publication statusPublished - 13-Feb-2020


  • branched chain amino acids
  • post-transplant diabetes mellitus
  • biomarker
  • renal transplant recipients

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