title: Differential metabolic impact of gastric bypass surgery versus dietary intervention in obese diabetic subjects despite identical weight loss.
abstract: Glycemic control is improved more after gastric bypass surgery (GBP) than after equivalent diet-induced weight loss in patients with morbid obesity and type 2 diabetes mellitus. We applied metabolomic profiling to understand the mechanisms of this better metabolic response after GBP. Circulating amino acids (AAs) and acylcarnitines (ACs) were measured in plasma from fasted subjects by targeted tandem mass spectrometry before and after a matched 10-kilogram weight loss induced by GBP or diet. Total AAs and branched-chain AAs (BCAAs) decreased after GBP, but not after dietary intervention. Metabolites derived from BCAA oxidation also decreased only after GBP. Principal components (PC) analysis identified two major PCs, one composed almost exclusively of ACs (PC1) and another with BCAAs and their metabolites as major contributors (PC2). PC1 and PC2 were inversely correlated with pro-insulin concentrations, the C-peptide response to oral glucose, and the insulin sensitivity index after weight loss, whereas PC2 was uniquely correlated with levels of insulin resistance (HOMA-IR). These data suggest that the enhanced decrease in circulating AAs after GBP occurs by mechanisms other than weight loss and may contribute to the better improvement in glucose homeostasis observed with the surgical intervention.
authors.affiliation: New York Obesity Nutrition Research Center, St. Luke's Roosevelt Hospital Center, New York, NY 10025, USA. bbl14@columbia.edu
authors.forename: Blandine
authors.initials: B
authors.lastname: Laferrère
authors.forename: David
authors.initials: D
authors.lastname: Reilly
authors.forename: Sara
authors.initials: S
authors.lastname: Arias
authors.forename: Nicholas
authors.initials: N
authors.lastname: Swerdlow
authors.forename: Prakash
authors.initials: P
authors.lastname: Gorroochurn
authors.forename: Baani
authors.initials: B
authors.lastname: Bawa
authors.forename: Mousumi
authors.initials: M
authors.lastname: Bose
authors.forename: Julio
authors.initials: J
authors.lastname: Teixeira
authors.forename: Robert D
authors.initials: RD
authors.lastname: Stevens
authors.forename: Brett R
authors.initials: BR
authors.lastname: Wenner
authors.forename: James R
authors.initials: JR
authors.lastname: Bain
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Muehlbauer
authors.forename: Andrea
authors.initials: A
authors.lastname: Haqq
authors.forename: Lillian
authors.initials: L
authors.lastname: Lien
authors.forename: Svati H
authors.initials: SH
authors.lastname: Shah
authors.forename: Laura P
authors.initials: LP
authors.lastname: Svetkey
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Newgard
mesh_terms: D000328:Adult; D000597:Amino Acids, Branched-Chain / Q000097:blood; D002331:Carnitine / Q000031:analogs & derivatives / Q000097:blood; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000178:diet therapy* / Q000378:metabolism*; D005260:Female; D015390:Gastric Bypass; D006801:Humans; D008297:Male; D053858:Metabolic Networks and Pathways; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000178:diet therapy* / Q000378:metabolism* / Q000601:surgery; D025341:Principal Component Analysis; D012044:Regression Analysis; D015431:Weight Loss / Q000502:physiology*
chemical_list: D000597:Amino Acids, Branched-Chain; C116917:acylcarnitine; D002331:Carnitine