@article{c2f01b82c1074fbfba0434e8af45e36f,
title = "Carnitine supplementation improves metabolic flexibility and skeletal muscle acetylcarnitine formation in volunteers with impaired glucose tolerance: A randomised controlled trial",
abstract = "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/m(2)/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 (H-1-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. (c) 2019 The Author(s). Published by Elsevier B.V.",
keywords = "L-carnitine, Metabolic flexibility, Insulin sensitivity, Acetylcarnitine, Impaired glucose tolerance, Hyperinsulinemic-euglycemic clamp, HYPERINSULINEMIC-EUGLYCEMIC CLAMP, INSULIN SENSITIVITY, FUEL METABOLISM, RESISTANCE, PLASMA, QUANTIFICATION, DISPOSAL, PROFILE, DIET, COA",
author = "Bruls, {Yvonne M. H.} and {de Ligt}, Marlies and Lucas Lindeboom and Esther Phielix and Bas Havekes and Gert Schaart and Esther Kornips and Wildberger, {Joachim E.} and Hesselink, {Matthijs K. C.} and Deborah Muoio and Patrick Schrauwen and Schrauwen-Hinderling, {Vera B.}",
note = "Funding Information: This study was funded by a European Foundation for the Study of Diabetes Clinical Research Grant. Vera Schrauwen-Hinderling was supported by a grant from the European Research Council (ERC-2017-StG-75961 MRS in diabetes. The authors greatly thank all research volunteers for participating in the study.The authors would like to thank Fred Vaz from the Core Facility Metabolomics of the Amsterdam University Medical Center for his help with analyzing the acetylcarnitine species. The funding source did not play a role other than financial support. 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 as suggested based on animal studies. Whether carnitine supplementation can also improve metabolic flexibility in humans has so far not been studied. Therefore, we investigated whether carnitine supplementation improves metabolic flexibility and insulin sensitivity in impaired glucose tolerant (IGT) volunteers. Metabolic flexibility was completely restored upon carnitine supplementation in IGT volunteers. Furthermore, carnitine enhanced the increase in resting skeletal muscle acetylcarnitine concentrations over the day (delta 7:00 AM-5:00 PM). Long-chain acylcarnitine species were reduced after carnitine supplementation, suggesting the stimulation of a more complete fat oxidation in muscle. Carnitine supplementation may provide new opportunities in the prevention and/or treatment of type 2 diabetes which require further investigation. Funding Information: This study was funded by a European Foundation for the Study of Diabetes Clinical Research Grant. Vera Schrauwen-Hinderling was supported by a grant from the European Research Council (ERC-2017-StG-75961 MRS in diabetes. The authors greatly thank all research volunteers for participating in the study.The authors would like to thank Fred Vaz from the Core Facility Metabolomics of the Amsterdam University Medical Center for his help with analyzing the acetylcarnitine species. Publisher Copyright: {\textcopyright} 2019 The Author(s)",
year = "2019",
month = nov,
doi = "10.1016/j.ebiom.2019.10.017",
language = "English",
volume = "49",
pages = "318--330",
journal = "EBioMedicine",
issn = "2352-3964",
publisher = "Elsevier B.V.",
}