PMID- 33079174
OWN - NLM
STAT- MEDLINE
DCOM- 20211019
LR  - 20211019
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Linking)
VI  - 106
IP  - 4
DP  - 2021 Mar 25
TI  - Elevated Plasma Branched-Chain Amino Acid Levels Correlate With Type 2 
      Diabetes-Related Metabolic Disturbances.
PG  - e1827-e1836
LID - 10.1210/clinem/dgaa751 [doi]
AB  - 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/m2). 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 1-13C 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 mumol kg-1 min-1, P < .05) and 
      tended to be lower during high insulin infusion (0.326 +/- 0.024 vs 0.382 +/- 0.013 
      mumol 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.
CI  - (c) The Author(s) 2020. Published by Oxford University Press on behalf of the 
      Endocrine Society. All rights reserved. For permissions, please e-mail: 
      journals.permissions@oup.com.
FAU - Vanweert, Froukje
AU  - Vanweert F
AD  - Department of Nutrition and Movement Sciences, Maastricht University and Medical 
      Center, Maastricht, the Netherlands.
AD  - NUTRIM, School of Nutrition and Translational Research in Metabolism, Maastricht 
      University and Medical Center, Maastricht, the Netherlands.
FAU - de Ligt, Marlies
AU  - de Ligt M
AD  - Department of Nutrition and Movement Sciences, Maastricht University and Medical 
      Center, Maastricht, the Netherlands.
AD  - NUTRIM, School of Nutrition and Translational Research in Metabolism, Maastricht 
      University and Medical Center, Maastricht, the Netherlands.
FAU - Hoeks, Joris
AU  - Hoeks J
AD  - Department of Nutrition and Movement Sciences, Maastricht University and Medical 
      Center, Maastricht, the Netherlands.
AD  - NUTRIM, School of Nutrition and Translational Research in Metabolism, Maastricht 
      University and Medical Center, Maastricht, the Netherlands.
FAU - Hesselink, Matthijs K C
AU  - Hesselink MKC
AD  - Department of Nutrition and Movement Sciences, Maastricht University and Medical 
      Center, Maastricht, the Netherlands.
AD  - NUTRIM, School of Nutrition and Translational Research in Metabolism, Maastricht 
      University and Medical Center, Maastricht, the Netherlands.
FAU - Schrauwen, Patrick
AU  - Schrauwen P
AD  - Department of Nutrition and Movement Sciences, Maastricht University and Medical 
      Center, Maastricht, the Netherlands.
AD  - NUTRIM, School of Nutrition and Translational Research in Metabolism, Maastricht 
      University and Medical Center, Maastricht, the Netherlands.
FAU - Phielix, Esther
AU  - Phielix E
AD  - Department of Nutrition and Movement Sciences, Maastricht University and Medical 
      Center, Maastricht, the Netherlands.
AD  - NUTRIM, School of Nutrition and Translational Research in Metabolism, Maastricht 
      University and Medical Center, Maastricht, the Netherlands.
LA  - eng
SI  - NTR/NTR4181
PT  - Journal Article
PT  - Observational Study
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Amino Acids, Branched-Chain)
RN  - GMW67QNF9C (Leucine)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Amino Acids, Branched-Chain/*blood
MH  - Case-Control Studies
MH  - Diabetes Complications/blood/diagnosis/metabolism
MH  - Diabetes Mellitus, Type 2/*blood/complications/metabolism
MH  - Female
MH  - Humans
MH  - Insulin Resistance/physiology
MH  - Leucine/metabolism
MH  - Male
MH  - Metabolic Diseases/*blood/diagnosis/etiology
MH  - Middle Aged
MH  - Mitochondria/metabolism
MH  - Oxidation-Reduction
OTO - NOTNLM
OT  - 1-13C leucine oxidation
OT  - branched-chain amino acids
OT  - first-degree relatives
OT  - insulin resistance
OT  - mitochondrial oxidative capacity
OT  - type 2 diabetes
EDAT- 2020/10/21 06:00
MHDA- 2021/10/21 06:00
CRDT- 2020/10/20 12:12
PHST- 2020/08/08 00:00 [received]
PHST- 2020/10/14 00:00 [accepted]
PHST- 2020/10/21 06:00 [pubmed]
PHST- 2021/10/21 06:00 [medline]
PHST- 2020/10/20 12:12 [entrez]
AID - 5932347 [pii]
AID - 10.1210/clinem/dgaa751 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2021 Mar 25;106(4):e1827-e1836. doi: 
      10.1210/clinem/dgaa751.