Metabolic phenotyping to provide insight in mechanisms underlying muscle weakness and wasting in patients with cancer

Barbara S Van der Meij, Nicolaas Deutz, Ramon Rodriguez, Fari Koeman, Tiffany Smit, Marielle Engelen

Research output: Contribution to journalMeeting AbstractResearchpeer-review

Abstract

Rationale: Cancer is characterized by low plasma concentrations of arginine (ARG), glutamine (GLN) and citrulline (CIT). This study investigates the relationship between glutamine-related metabolism and muscle strength in patients with advanced cancer using metabolic phenotyping.
Methods: In 16 patients with solid tumours (C) and 16 age- and gender-matched healthy controls (H), fasted plasma amino acid concentrations and whole body ARG, GLN, CIT and GLU rates of appearance (Ra) were assessed by pulse IV administration of L-[Guanidino-15N2]-Arginine, L-[5-15N]-glutamine, L-[ureido-13C-2H2]-Citrulline, L-[1,2-13C2] Glutamate and 2H3-Leucine (LEU), and clearance rates calculated. Handgrip, inspiratory and leg muscle strength and physical function (EORTC-QLQc30 questionnaire) were assessed, and amino acid concentrations and isotope enrichments by LCMS/MS. Statistics was done by unpaired t-tests and spearman correlation tests.
Results: Ra and clearance rate of GLN were higher in C than in H (Ra GLN: 491.4±32.0 vs. 325.2±51.5 μmol/kg ffm/h, p=0.008, clearance GLN 1.13±0.08 vs 0.70±0.09, p<0.001) as well as that of the GLN related amino acids ARG, CIT and LEU (p<0.05). The conversion of ARG to CIT (marker of NO synthesis), CIT to ARG (de novo ARG production) and GLU to GLN (marker of muscle GLN production) were also higher in C (P<0.01) and negatively correlated to FFMi (r<-0.5, P<0.05). Plasma BCAA was positively correlated to handgrip and inspiratory muscle strength, and physical function (R>0.4, P<0.05). RaCIT was negatively related to leg extension strength (r=-0.7, P<0.01).
Conclusion: Metabolic phenotyping using novel tracer pulse methodology showed that disturbances in glutamine related metabolism are associated with muscle wasting and weakness in patients with cancer.
Original languageEnglish
Pages (from-to)S156
JournalClinical Nutrition
Volume36
Issue numberS1
DOIs
Publication statusPublished - Sep 2017
EventThe 39th European Society for Clinical Nutrition and Metabolism Congress 2017 - Hague, Netherlands
Duration: 9 Sep 201712 Sep 2017
Conference number: 39
http://www.espen.org/congress/next-congresses/12-espen/index.php?option=com_content&view=article&id=214&Itemid=1052

Fingerprint

Muscle Weakness
Glutamine
Citrulline
Neoplasms
Arginine
Muscle Strength
Leg
Leucine
Isotopes
Glutamic Acid
Amino Acids
Acids

Cite this

Van der Meij, Barbara S ; Deutz, Nicolaas ; Rodriguez, Ramon ; Koeman, Fari ; Smit, Tiffany ; Engelen, Marielle. / Metabolic phenotyping to provide insight in mechanisms underlying muscle weakness and wasting in patients with cancer. In: Clinical Nutrition. 2017 ; Vol. 36, No. S1. pp. S156.
@article{f8b746b6dc85401b8f7f7796d0d572a7,
title = "Metabolic phenotyping to provide insight in mechanisms underlying muscle weakness and wasting in patients with cancer",
abstract = "Rationale: Cancer is characterized by low plasma concentrations of arginine (ARG), glutamine (GLN) and citrulline (CIT). This study investigates the relationship between glutamine-related metabolism and muscle strength in patients with advanced cancer using metabolic phenotyping.Methods: In 16 patients with solid tumours (C) and 16 age- and gender-matched healthy controls (H), fasted plasma amino acid concentrations and whole body ARG, GLN, CIT and GLU rates of appearance (Ra) were assessed by pulse IV administration of L-[Guanidino-15N2]-Arginine, L-[5-15N]-glutamine, L-[ureido-13C-2H2]-Citrulline, L-[1,2-13C2] Glutamate and 2H3-Leucine (LEU), and clearance rates calculated. Handgrip, inspiratory and leg muscle strength and physical function (EORTC-QLQc30 questionnaire) were assessed, and amino acid concentrations and isotope enrichments by LCMS/MS. Statistics was done by unpaired t-tests and spearman correlation tests.Results: Ra and clearance rate of GLN were higher in C than in H (Ra GLN: 491.4±32.0 vs. 325.2±51.5 μmol/kg ffm/h, p=0.008, clearance GLN 1.13±0.08 vs 0.70±0.09, p<0.001) as well as that of the GLN related amino acids ARG, CIT and LEU (p<0.05). The conversion of ARG to CIT (marker of NO synthesis), CIT to ARG (de novo ARG production) and GLU to GLN (marker of muscle GLN production) were also higher in C (P<0.01) and negatively correlated to FFMi (r<-0.5, P<0.05). Plasma BCAA was positively correlated to handgrip and inspiratory muscle strength, and physical function (R>0.4, P<0.05). RaCIT was negatively related to leg extension strength (r=-0.7, P<0.01).Conclusion: Metabolic phenotyping using novel tracer pulse methodology showed that disturbances in glutamine related metabolism are associated with muscle wasting and weakness in patients with cancer.",
author = "{Van der Meij}, {Barbara S} and Nicolaas Deutz and Ramon Rodriguez and Fari Koeman and Tiffany Smit and Marielle Engelen",
year = "2017",
month = "9",
doi = "10.1016/S0261-5614(17)30353-9",
language = "English",
volume = "36",
pages = "S156",
journal = "Clinical Nutrition",
issn = "0261-5614",
publisher = "Churchill Livingstone",
number = "S1",

}

Metabolic phenotyping to provide insight in mechanisms underlying muscle weakness and wasting in patients with cancer. / Van der Meij, Barbara S; Deutz, Nicolaas; Rodriguez, Ramon; Koeman, Fari; Smit, Tiffany; Engelen, Marielle.

In: Clinical Nutrition, Vol. 36, No. S1, 09.2017, p. S156.

Research output: Contribution to journalMeeting AbstractResearchpeer-review

TY - JOUR

T1 - Metabolic phenotyping to provide insight in mechanisms underlying muscle weakness and wasting in patients with cancer

AU - Van der Meij, Barbara S

AU - Deutz, Nicolaas

AU - Rodriguez, Ramon

AU - Koeman, Fari

AU - Smit, Tiffany

AU - Engelen, Marielle

PY - 2017/9

Y1 - 2017/9

N2 - Rationale: Cancer is characterized by low plasma concentrations of arginine (ARG), glutamine (GLN) and citrulline (CIT). This study investigates the relationship between glutamine-related metabolism and muscle strength in patients with advanced cancer using metabolic phenotyping.Methods: In 16 patients with solid tumours (C) and 16 age- and gender-matched healthy controls (H), fasted plasma amino acid concentrations and whole body ARG, GLN, CIT and GLU rates of appearance (Ra) were assessed by pulse IV administration of L-[Guanidino-15N2]-Arginine, L-[5-15N]-glutamine, L-[ureido-13C-2H2]-Citrulline, L-[1,2-13C2] Glutamate and 2H3-Leucine (LEU), and clearance rates calculated. Handgrip, inspiratory and leg muscle strength and physical function (EORTC-QLQc30 questionnaire) were assessed, and amino acid concentrations and isotope enrichments by LCMS/MS. Statistics was done by unpaired t-tests and spearman correlation tests.Results: Ra and clearance rate of GLN were higher in C than in H (Ra GLN: 491.4±32.0 vs. 325.2±51.5 μmol/kg ffm/h, p=0.008, clearance GLN 1.13±0.08 vs 0.70±0.09, p<0.001) as well as that of the GLN related amino acids ARG, CIT and LEU (p<0.05). The conversion of ARG to CIT (marker of NO synthesis), CIT to ARG (de novo ARG production) and GLU to GLN (marker of muscle GLN production) were also higher in C (P<0.01) and negatively correlated to FFMi (r<-0.5, P<0.05). Plasma BCAA was positively correlated to handgrip and inspiratory muscle strength, and physical function (R>0.4, P<0.05). RaCIT was negatively related to leg extension strength (r=-0.7, P<0.01).Conclusion: Metabolic phenotyping using novel tracer pulse methodology showed that disturbances in glutamine related metabolism are associated with muscle wasting and weakness in patients with cancer.

AB - Rationale: Cancer is characterized by low plasma concentrations of arginine (ARG), glutamine (GLN) and citrulline (CIT). This study investigates the relationship between glutamine-related metabolism and muscle strength in patients with advanced cancer using metabolic phenotyping.Methods: In 16 patients with solid tumours (C) and 16 age- and gender-matched healthy controls (H), fasted plasma amino acid concentrations and whole body ARG, GLN, CIT and GLU rates of appearance (Ra) were assessed by pulse IV administration of L-[Guanidino-15N2]-Arginine, L-[5-15N]-glutamine, L-[ureido-13C-2H2]-Citrulline, L-[1,2-13C2] Glutamate and 2H3-Leucine (LEU), and clearance rates calculated. Handgrip, inspiratory and leg muscle strength and physical function (EORTC-QLQc30 questionnaire) were assessed, and amino acid concentrations and isotope enrichments by LCMS/MS. Statistics was done by unpaired t-tests and spearman correlation tests.Results: Ra and clearance rate of GLN were higher in C than in H (Ra GLN: 491.4±32.0 vs. 325.2±51.5 μmol/kg ffm/h, p=0.008, clearance GLN 1.13±0.08 vs 0.70±0.09, p<0.001) as well as that of the GLN related amino acids ARG, CIT and LEU (p<0.05). The conversion of ARG to CIT (marker of NO synthesis), CIT to ARG (de novo ARG production) and GLU to GLN (marker of muscle GLN production) were also higher in C (P<0.01) and negatively correlated to FFMi (r<-0.5, P<0.05). Plasma BCAA was positively correlated to handgrip and inspiratory muscle strength, and physical function (R>0.4, P<0.05). RaCIT was negatively related to leg extension strength (r=-0.7, P<0.01).Conclusion: Metabolic phenotyping using novel tracer pulse methodology showed that disturbances in glutamine related metabolism are associated with muscle wasting and weakness in patients with cancer.

U2 - 10.1016/S0261-5614(17)30353-9

DO - 10.1016/S0261-5614(17)30353-9

M3 - Meeting Abstract

VL - 36

SP - S156

JO - Clinical Nutrition

JF - Clinical Nutrition

SN - 0261-5614

IS - S1

ER -