TY - JOUR
T1 - The Effect of Standard Versus Longer Intestinal Bypass on GLP-1 Regulation and Glucose Metabolism in Patients With Type 2 Diabetes Undergoing Roux-en-Y Gastric Bypass
T2 - The Long-Limb Study
AU - Miras, Alexander Dimitri
AU - Kamocka, Anna
AU - Pérez-Pevida, Belén
AU - Purkayastha, Sanjay
AU - Moorthy, Krishna
AU - Patel, Ameet
AU - Chahal, Harvinder
AU - Frost, Gary
AU - Bassett, Paul
AU - Castagnetto-Gissey, Lidia
AU - Coppin, Lucy
AU - Jackson, Nicola
AU - Umpleby, Anne Margot
AU - Bloom, Stephen Robert
AU - Tan, Tricia
AU - Ahmed, Ahmed Rashid
AU - Rubino, Francesco
N1 - Funding Information:
This research was funded by the National Institute for Health Research (NIHR) Efficacy and Mechanism Evaluation Programme (EME 13/121/0). Infrastructure support was provided by the NIHR Imperial Biomedical Research Centre, the NIHR Imperial Clinical Research Facility, and NIHR King?s Clinical Research Facility. The Section of Endocrinology and Investigative Medicine is funded by grants from the Medical Research Council, Biotechnology and Biological Sciences Research Council, NIHR, an Integrative Mammalian Biology Capacity Building Award, an FP7-HEALTH-2009-241592 EuroCHIP grant, and is supported by the NIHR Biomedical Research Centre Funding Scheme. A.K. is also funded by the Research Fellowship of the Royal College of Surgeons.
Funding Information:
Acknowledgements. Julian Marchesi and Elaine Holmes (Imperial College London) were co-investigators, currently collaborating on further analysis, which includes the gut microbiota data. The authors acknowledge Brett Johnson, Madhawi Aldhwayan, Yoshiko Ishisa-ka, Ashwin Sundaram, Ioannis Lempesis, Va-sha Kaur, Zahraa Al-Mayahi, Kevin Quartey, Ahmed Rabie, Rhian Houghton, Kleopatra Alexiadou, Joyceline Quenco, Micaela Cortini, Anastasia Kopanou, the entire Imperial Weight Centre team, Spyros Panagiotopoulos, Elisa Galfrascoli, Francesco Villa, Arasteh Rey-hani, Barbara Petronio, James Casella Mariolo, Elina Akalestou, and Fariba Shojaee-Moradie. The authors thank the patients who took part in the trial and all the staff at the Imperial Weight Centre. Funding. This research was funded by the National Institute for Health Research (NIHR) Efficacy and Mechanism Evaluation Programme (EME 13/121/0). Infrastructure support was provided by the NIHR Imperial Biomedical Research Centre, the NIHR Imperial Clinical Research Facility, and NIHR King’s Clinical Research Facility. The Section of Endocrinology and Investigative Medicine is funded by grants from the Medical Research Council, Biotechnology and Biological Sciences Research Council, NIHR, an Integrative Mammalian Biology Capacity Building Award, an FP7-HEALTH-2009-241592 EuroCHIP grant, and is supported by the NIHR Biomedical Research Centre Funding Scheme. A.K. is also funded by the Research Fellowship of the Royal College of Surgeons.
Publisher Copyright:
© 2020 by the American Diabetes Association.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/5/1
Y1 - 2021/5/1
N2 - OBJECTIVE: Roux-en-Y gastric bypass (RYGB) characteristically enhances postprandial levels of glucagon-like peptide 1 (GLP-1), a mechanism that contributes to its profound glucose-lowering effects. This enhancement is thought to be triggered by bypass of food to the distal small intestine with higher densities of neuroendocrine L-cells. We hypothesized that if this is the predominant mechanism behind the enhanced secretion of GLP-1, a longer intestinal bypass would potentiate the postprandial peak in GLP-1, translating into higher insulin secretion and, thus, additional improvements in glucose tolerance. To investigate this, we conducted a mechanistic study comparing two variants of RYGB that differ in the length of intestinal bypass. RESEARCH DESIGN AND METHODS: A total of 53 patients with type 2 diabetes (T2D) and obesity were randomized to either standard limb RYGB (50-cm biliopancreatic limb) or long limb RYGB (150-cm biliopancreatic limb). They underwent measurements of GLP-1 and insulin secretion following a mixed meal and insulin sensitivity using euglycemic hyperinsulinemic clamps at baseline and 2 weeks and at 20% weight loss after surgery. RESULTS: Both groups exhibited enhancement in postprandial GLP-1 secretion and improvements in glycemia compared with baseline. There were no significant differences in postprandial peak concentrations of GLP-1, time to peak, insulin secretion, and insulin sensitivity. CONCLUSIONS: The findings of this study demonstrate that lengthening of the intestinal bypass in RYGB does not affect GLP-1 secretion. Thus, the characteristic enhancement of GLP-1 response after RYGB might not depend on delivery of nutrients to more distal intestinal segments.
AB - OBJECTIVE: Roux-en-Y gastric bypass (RYGB) characteristically enhances postprandial levels of glucagon-like peptide 1 (GLP-1), a mechanism that contributes to its profound glucose-lowering effects. This enhancement is thought to be triggered by bypass of food to the distal small intestine with higher densities of neuroendocrine L-cells. We hypothesized that if this is the predominant mechanism behind the enhanced secretion of GLP-1, a longer intestinal bypass would potentiate the postprandial peak in GLP-1, translating into higher insulin secretion and, thus, additional improvements in glucose tolerance. To investigate this, we conducted a mechanistic study comparing two variants of RYGB that differ in the length of intestinal bypass. RESEARCH DESIGN AND METHODS: A total of 53 patients with type 2 diabetes (T2D) and obesity were randomized to either standard limb RYGB (50-cm biliopancreatic limb) or long limb RYGB (150-cm biliopancreatic limb). They underwent measurements of GLP-1 and insulin secretion following a mixed meal and insulin sensitivity using euglycemic hyperinsulinemic clamps at baseline and 2 weeks and at 20% weight loss after surgery. RESULTS: Both groups exhibited enhancement in postprandial GLP-1 secretion and improvements in glycemia compared with baseline. There were no significant differences in postprandial peak concentrations of GLP-1, time to peak, insulin secretion, and insulin sensitivity. CONCLUSIONS: The findings of this study demonstrate that lengthening of the intestinal bypass in RYGB does not affect GLP-1 secretion. Thus, the characteristic enhancement of GLP-1 response after RYGB might not depend on delivery of nutrients to more distal intestinal segments.
UR - http://www.scopus.com/inward/record.url?scp=85106539737&partnerID=8YFLogxK
U2 - 10.2337/dc20-0762
DO - 10.2337/dc20-0762
M3 - Article
C2 - 33158945
AN - SCOPUS:85106539737
SN - 0149-5992
VL - 44
SP - 1082
EP - 1090
JO - Diabetes Care
JF - Diabetes Care
IS - 5
ER -