Elevated Plasma Branched-Chain Amino Acid Levels Correlate With Type 2 Diabetes-Related Metabolic Disturbances

F. Vanweert, M. de Ligt, J. Hoeks, M.K.C. Hesselink, P. Schrauwen, E. Phielix*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

10 Citations (Web of Science)


Context: Patients with type 2 diabetes mellitus (T2DM) have elevated plasma branched-chain amino acid (BCAA) levels. The underlying cause, however, is not known. Low mitochondrial oxidation of BCAA levels could contribute to higher plasma BCAA levels.

Objective: We aimed to investigate ex vivo muscle mitochondrial oxidative capacity and in vivo BCAA oxidation measured by whole-body leucine oxidation rates in patients with T2DM, first-degree relatives (FDRs), and control participants (CONs) with overweight or obesity.

Design and Setting: An observational, community-based study was conducted.

Participants: Fifteen patients with T2DM, 13 FDR, and 17 CONs were included (age, 40-70 years; body mass index, 27-35 kg/m(2)).

Main Outcome Measures: High-resolution respirometry was used to examine ex vivo mitochondrial oxidative capacity in permeabilized muscle fibers. A subgroup of 5 T2DM patients and 5 CONs underwent hyperinsulinemic-euglycemic clamps combined with 1-C-13 leucine-infusion to determine whole-body leucine oxidation.

Results: Total BCAA levels were higher in patients with T2DM compared to CONs, but not in FDRs, and correlated negatively with muscle mitochondrial oxidative capacity (r = -0.44, P < .001). Consistently, whole-body leucine oxidation rate was lower in patients with T2DM vs CON under basal conditions (0.202 +/- 0.049 vs 0.275 +/- 0.043 mu mol kg(-1) min(-1), P < .05) and tended to be lower during high insulin infusion (0.326 +/- 0.024 vs 0.382 +/- 0.013 mu mol kg(-1) min(-1), P = .075).

Conclusions: In patients with T2DM, a compromised whole-body leucine oxidation rate supports our hypothesis that higher plasma BCAA levels may originate at least partly from a low mitochondrial oxidative capacity.

Original languageEnglish
Pages (from-to)E1827-E1836
Number of pages10
JournalJournal of Clinical Endocrinology & Metabolism
Issue number4
Publication statusPublished - 1 Apr 2021


  • branched-chain amino acids
  • type 2 diabetes
  • mitochondrial oxidative capacity
  • first-degree relatives
  • insulin resistance
  • 1-C-13 leucine oxidation

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