Claire L Meek1, Frank Reimann2, Adrian J Park3, Fiona M Gribble2. 1. University of Cambridge, Cambridge, UK. Electronic address: clm70@cam.ac.uk. 2. University of Cambridge, Cambridge, UK. 3. Addenbrooke's Hospital, Cambridge, UK.
Abstract
BACKGROUND: Obesity is a global concern and can be effectively treated with bariatric surgery, which is expensive and invasive. Weight loss after surgery has been attributed to increased nutrient delivery to the lower small intestine with release of satiety-promoting gut hormones such as glucagon-like peptide 1 (GLP-1). We aimed to assess whether glutamine, a potent secretagogue of GLP-1 in vivo, increases GLP-1 release, improves glucose tolerance, or reduces meal size in volunteers. METHODS: A single-centre, randomised, double blind, placebo-controlled, cross-over study was performed in Cambridge, UK, studying the effects of a single dose of encapsulated ileal-release glutamine (6 g) and placebo (microcrystalline cellulose) in healthy adult volunteers. Volunteers were recruited for each endpoint and received each regimen in random order (performed by electronic random number generation). The primary outcome was within-person GLP-1 in venous blood (concentrations and area under the curve). Secondary outcomes were glucose tolerance (measured with an oral glucose tolerance test given after 90 min) and meal size (ad-libitum meal given at 120 min). Inclusion of 8-10 participants for each endpoint would achieve 90% power with α at 0·05. Significance testing was done with the paired t test. Participants gave written informed consent and the study was approved by the local research ethics committee. This trial is registered with the ISRCTN register, number ISRCTN10757078. FINDINGS:11 men and 13 women were recruited (aged 22-58 years, body-mass index 18·5-31·8 kg/m(2)). Ten patients were assigned to assessment of GLP-1, eight to assessment of glucose tolerance, and ten for meal size. Some volunteers participated in more than one part of the study. Ingestion of 6 g glutamine was associated with increased GLP-1 concentrations after 90 min compared with placebo (mean 3·2 pmol/L [SD 0·86] vs 2·1 [0·65], p=0·004), increased insulin concentrations after 90 min (70·9 [37·9] vs 51·5 [23·1], p=0·048), and increased meal size at 120 min (542 g eaten [188] vs 481 [193], p=0·008). No safety concerns were identified after the ingestion of glutamine. INTERPRETATION: This trial shows that a single oral dose of encapsulated glutamine can promote increased secretion of GLP-1 and is associated with increased insulin release. However, the effect size was small and unlikely to be clinically useful. Glutamine was associated with increased meal size, an undesirable effect, perhaps because the orexigenic effects of insulin release predominated over the anorexigenic effects of GLP-1 release after administration of glutamine. FUNDING: European Union's Seventh Framework Programme, Wellcome Trust Translational Medicine & Therapeutics Programme, National Institute for Health Research.
RCT Entities:
BACKGROUND: Obesity is a global concern and can be effectively treated with bariatric surgery, which is expensive and invasive. Weight loss after surgery has been attributed to increased nutrient delivery to the lower small intestine with release of satiety-promoting gut hormones such as glucagon-like peptide 1 (GLP-1). We aimed to assess whether glutamine, a potent secretagogue of GLP-1 in vivo, increases GLP-1 release, improves glucose tolerance, or reduces meal size in volunteers. METHODS: A single-centre, randomised, double blind, placebo-controlled, cross-over study was performed in Cambridge, UK, studying the effects of a single dose of encapsulated ileal-release glutamine (6 g) and placebo (microcrystalline cellulose) in healthy adult volunteers. Volunteers were recruited for each endpoint and received each regimen in random order (performed by electronic random number generation). The primary outcome was within-personGLP-1 in venous blood (concentrations and area under the curve). Secondary outcomes were glucose tolerance (measured with an oral glucose tolerance test given after 90 min) and meal size (ad-libitum meal given at 120 min). Inclusion of 8-10 participants for each endpoint would achieve 90% power with α at 0·05. Significance testing was done with the paired t test. Participants gave written informed consent and the study was approved by the local research ethics committee. This trial is registered with the ISRCTN register, number ISRCTN10757078. FINDINGS: 11 men and 13 women were recruited (aged 22-58 years, body-mass index 18·5-31·8 kg/m(2)). Ten patients were assigned to assessment of GLP-1, eight to assessment of glucose tolerance, and ten for meal size. Some volunteers participated in more than one part of the study. Ingestion of 6 g glutamine was associated with increased GLP-1 concentrations after 90 min compared with placebo (mean 3·2 pmol/L [SD 0·86] vs 2·1 [0·65], p=0·004), increased insulin concentrations after 90 min (70·9 [37·9] vs 51·5 [23·1], p=0·048), and increased meal size at 120 min (542 g eaten [188] vs 481 [193], p=0·008). No safety concerns were identified after the ingestion of glutamine. INTERPRETATION: This trial shows that a single oral dose of encapsulated glutamine can promote increased secretion of GLP-1 and is associated with increased insulin release. However, the effect size was small and unlikely to be clinically useful. Glutamine was associated with increased meal size, an undesirable effect, perhaps because the orexigenic effects of insulin release predominated over the anorexigenic effects of GLP-1 release after administration of glutamine. FUNDING: European Union's Seventh Framework Programme, Wellcome Trust Translational Medicine & Therapeutics Programme, National Institute for Health Research.
Authors: Anjali Amin; Christina Neophytou; Shermaine Thein; Niamh M Martin; Amin Alamshah; Eleanor Spreckley; Stephen R Bloom; Kevin G Murphy Journal: Obesity (Silver Spring) Date: 2018-11 Impact factor: 5.002