title: GLP-1 plays a limited role in improved glycemia shortly after Roux-en-Y gastric bypass: a comparison with intensive lifestyle modification.
abstract: Rapid glycemic improvements following Roux-en-Y gastric bypass (RYGB) are frequently attributed to the enhanced GLP-1 response, but causality remains unclear. To determine the role of GLP-1 in improved glucose tolerance after surgery, we compared glucose and hormonal responses to a liquid meal test in 20 obese participants with type 2 diabetes mellitus who underwent RYGB or nonsurgical intensive lifestyle modification (ILM) (n = 10 per group) before and after equivalent short-term weight reduction. The GLP-1 receptor antagonist exendin(9-39)-amide (Ex-9) was administered, in random order and in double-blinded fashion, with saline during two separate visits after equivalent weight loss. Despite the markedly exaggerated GLP-1 response after RYGB, changes in postprandial glucose and insulin responses did not significantly differ between groups, and glucagon secretion was paradoxically augmented after RYGB. Hepatic insulin sensitivity also increased significantly after RYGB. With Ex-9, glucose tolerance deteriorated similarly from the saline condition in both groups, but postprandial insulin release was markedly attenuated after RYGB compared with ILM. GLP-1 exerts important insulinotropic effects after RYGB and ILM, but the enhanced incretin response plays a limited role in improved glycemia shortly after surgery. Instead, enhanced hepatic metabolism, independent of GLP-1 receptor activation, may be more important for early postsurgical glycemic improvements.
authors.affiliation: Department of Medicine, Institute for Diabetes, Obesity and Metabolism, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA Department of Psychiatry, Center for Weight and Eating Disorders, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA marion.vetter@bms.com.
authors.forename: Marion L
authors.initials: ML
authors.lastname: Vetter
authors.affiliation: Department of Psychiatry, Center for Weight and Eating Disorders, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Wadden
authors.affiliation: Monell Chemical Senses Center, Philadelphia, PA.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Teff
authors.affiliation: Department of Medicine, Institute for Diabetes, Obesity and Metabolism, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: Zahra F
authors.initials: ZF
authors.lastname: Khan
authors.affiliation: Department of Psychiatry, Center for Weight and Eating Disorders, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: Raymond
authors.initials: R
authors.lastname: Carvajal
authors.affiliation: Department of Psychiatry, Center for Weight and Eating Disorders, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: Scott
authors.initials: S
authors.lastname: Ritter
authors.affiliation: Department of Statistics, North Carolina State University, Raleigh, NC.
authors.forename: Reneé H
authors.initials: RH
authors.lastname: Moore
authors.affiliation: University of Pennsylvania School of Nursing, Philadelphia, PA.
authors.forename: Jesse L
authors.initials: JL
authors.lastname: Chittams
authors.affiliation: Department of Statistics, North Carolina State University, Raleigh, NC.
authors.forename: Alex
authors.initials: A
authors.lastname: Iagnocco
authors.affiliation: Department of Surgery, Division of Bariatric Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: Kenric
authors.initials: K
authors.lastname: Murayama
authors.affiliation: Department of Surgery, Division of Bariatric Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: Gary
authors.initials: G
authors.lastname: Korus
authors.affiliation: Department of Surgery, Division of Bariatric Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: Noel N
authors.initials: NN
authors.lastname: Williams
authors.affiliation: Department of Medicine, Institute for Diabetes, Obesity and Metabolism, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Rickels
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D005260:Female; D015390:Gastric Bypass; D052216:Glucagon-Like Peptide 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D054795:Incretins / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008019:Life Style; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000628:therapy
chemical_list: D001786:Blood Glucose; D054795:Incretins; D007328:Insulin; D052216:Glucagon-Like Peptide 1