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Carnitine supplementation improves metabolic flexibility and skeletal muscle acetylcarnitine formation in volunteers with impaired glucose tolerance: A randomised controlled trial.

Publication ,  Journal Article
Bruls, YM; de Ligt, M; Lindeboom, L; Phielix, E; Havekes, B; Schaart, G; Kornips, E; Wildberger, JE; Hesselink, MK; Muoio, D; Schrauwen, P ...
Published in: EBioMedicine
November 2019

BACKGROUND: Type 2 diabetes patients and individuals at risk of developing diabetes are characterized by metabolic inflexibility and disturbed glucose homeostasis. Low carnitine availability may contribute to metabolic inflexibility and impaired glucose tolerance. Here, we investigated whether carnitine supplementation improves metabolic flexibility and insulin sensitivity in impaired glucose tolerant (IGT) volunteers. METHODS: Eleven IGT- volunteers followed a 36-day placebo- and L-carnitine treatment (2 g/day) in a randomised, placebo-controlled, double blind crossover design. A hyperinsulinemic-euglycemic clamp (40 mU/m2/min), combined with indirect calorimetry (ventilated hood) was performed to determine insulin sensitivity and metabolic flexibility. Furthermore, metabolic flexibility was assessed in response to a high-energy meal. Skeletal muscle acetylcarnitine concentrations were measured in vivo using long echo time proton magnetic resonance spectroscopy (1H-MRS, TE=500 ms) in the resting state (7:00AM and 5:00PM) and after a 30-min cycling exercise. Twelve normal glucose tolerant (NGT) volunteers were included without any intervention as control group. RESULTS: Metabolic flexibility of IGT-subjects completely restored towards NGT control values upon carnitine supplementation, measured during a hyperinsulinemic-euglycemic clamp and meal test. In muscle, carnitine supplementation enhanced the increase in resting acetylcarnitine concentrations over the day (delta 7:00 AM versus 5:00 PM) in IGT-subjects. Furthermore, carnitine supplementation increased post-exercise acetylcarnitine concentrations and reduced long-chain acylcarnitine species in IGT-subjects, suggesting the stimulation of a more complete fat oxidation in muscle. Whole-body insulin sensitivity was not affected. CONCLUSION: Carnitine supplementation improves acetylcarnitine formation and rescues metabolic flexibility in IGT-subjects. Future research should investigate the potential of carnitine in prevention/treatment of type 2 diabetes.

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Published In

EBioMedicine

DOI

EISSN

2352-3964

Publication Date

November 2019

Volume

49

Start / End Page

318 / 330

Location

Netherlands

Related Subject Headings

  • Oxygen Consumption
  • Muscle, Skeletal
  • Middle Aged
  • Metabolome
  • Male
  • Kinetics
  • Insulin Resistance
  • Hyperinsulinism
  • Humans
  • Healthy Volunteers
 

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Bruls, Y. M., de Ligt, M., Lindeboom, L., Phielix, E., Havekes, B., Schaart, G., … Schrauwen-Hinderling, V. B. (2019). Carnitine supplementation improves metabolic flexibility and skeletal muscle acetylcarnitine formation in volunteers with impaired glucose tolerance: A randomised controlled trial. EBioMedicine, 49, 318–330. https://doi.org/10.1016/j.ebiom.2019.10.017
Bruls, Yvonne Mh, Marlies de Ligt, Lucas Lindeboom, Esther Phielix, Bas Havekes, Gert Schaart, Esther Kornips, et al. “Carnitine supplementation improves metabolic flexibility and skeletal muscle acetylcarnitine formation in volunteers with impaired glucose tolerance: A randomised controlled trial.EBioMedicine 49 (November 2019): 318–30. https://doi.org/10.1016/j.ebiom.2019.10.017.
Bruls, Yvonne Mh, et al. “Carnitine supplementation improves metabolic flexibility and skeletal muscle acetylcarnitine formation in volunteers with impaired glucose tolerance: A randomised controlled trial.EBioMedicine, vol. 49, Nov. 2019, pp. 318–30. Pubmed, doi:10.1016/j.ebiom.2019.10.017.
Bruls YM, de Ligt M, Lindeboom L, Phielix E, Havekes B, Schaart G, Kornips E, Wildberger JE, Hesselink MK, Muoio D, Schrauwen P, Schrauwen-Hinderling VB. Carnitine supplementation improves metabolic flexibility and skeletal muscle acetylcarnitine formation in volunteers with impaired glucose tolerance: A randomised controlled trial. EBioMedicine. 2019 Nov;49:318–330.
Journal cover image

Published In

EBioMedicine

DOI

EISSN

2352-3964

Publication Date

November 2019

Volume

49

Start / End Page

318 / 330

Location

Netherlands

Related Subject Headings

  • Oxygen Consumption
  • Muscle, Skeletal
  • Middle Aged
  • Metabolome
  • Male
  • Kinetics
  • Insulin Resistance
  • Hyperinsulinism
  • Humans
  • Healthy Volunteers