Differential metabolic impact of gastric bypass surgery versus dietary intervention in obese diabetic subjects despite identical weight loss

Blandine Laferrère, David Reilly, Sara Arias, Nicholas Swerdlow, Prakash Gorroochurn, Baani Bawa, Mousumi Bose, Julio Teixeira, Robert D. Stevens, Brett R. Wenner, James R. Bain, Michael J. Muehlbauer, Andrea Haqq, Lillian Lien, Svati H. Shah, Laura P. Svetkey, Christopher B. Newgard

Research output: Contribution to journalArticle

216 Citations (Scopus)

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.

Original languageEnglish
Article number80re2
JournalScience Translational Medicine
Volume3
Issue number80
DOIs
StatePublished - 27 Apr 2011

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Gastric Bypass
Weight Loss
Amino Acids
Insulin Resistance
Reducing Diet
Glucose
Branched Chain Amino Acids
Metabolomics
Morbid Obesity
C-Peptide
Tandem Mass Spectrometry
Principal Component Analysis
Type 2 Diabetes Mellitus
Homeostasis
Insulin
Diet

Cite this

Laferrère, Blandine ; Reilly, David ; Arias, Sara ; Swerdlow, Nicholas ; Gorroochurn, Prakash ; Bawa, Baani ; Bose, Mousumi ; Teixeira, Julio ; Stevens, Robert D. ; Wenner, Brett R. ; Bain, James R. ; Muehlbauer, Michael J. ; Haqq, Andrea ; Lien, Lillian ; Shah, Svati H. ; Svetkey, Laura P. ; Newgard, Christopher B. / Differential metabolic impact of gastric bypass surgery versus dietary intervention in obese diabetic subjects despite identical weight loss. In: Science Translational Medicine. 2011 ; Vol. 3, No. 80.
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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.",
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Laferrère, B, Reilly, D, Arias, S, Swerdlow, N, Gorroochurn, P, Bawa, B, Bose, M, Teixeira, J, Stevens, RD, Wenner, BR, Bain, JR, Muehlbauer, MJ, Haqq, A, Lien, L, Shah, SH, Svetkey, LP & Newgard, CB 2011, 'Differential metabolic impact of gastric bypass surgery versus dietary intervention in obese diabetic subjects despite identical weight loss', Science Translational Medicine, vol. 3, no. 80, 80re2. https://doi.org/10.1126/scitranslmed.3002043

Differential metabolic impact of gastric bypass surgery versus dietary intervention in obese diabetic subjects despite identical weight loss. / Laferrère, Blandine; Reilly, David; Arias, Sara; Swerdlow, Nicholas; Gorroochurn, Prakash; Bawa, Baani; Bose, Mousumi; Teixeira, Julio; Stevens, Robert D.; Wenner, Brett R.; Bain, James R.; Muehlbauer, Michael J.; Haqq, Andrea; Lien, Lillian; Shah, Svati H.; Svetkey, Laura P.; Newgard, Christopher B.

In: Science Translational Medicine, Vol. 3, No. 80, 80re2, 27.04.2011.

Research output: Contribution to journalArticle

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T1 - Differential metabolic impact of gastric bypass surgery versus dietary intervention in obese diabetic subjects despite identical weight loss

AU - Laferrère, Blandine

AU - Reilly, David

AU - Arias, Sara

AU - Swerdlow, Nicholas

AU - Gorroochurn, Prakash

AU - Bawa, Baani

AU - Bose, Mousumi

AU - Teixeira, Julio

AU - Stevens, Robert D.

AU - Wenner, Brett R.

AU - Bain, James R.

AU - Muehlbauer, Michael J.

AU - Haqq, Andrea

AU - Lien, Lillian

AU - Shah, Svati H.

AU - Svetkey, Laura P.

AU - Newgard, Christopher B.

PY - 2011/4/27

Y1 - 2011/4/27

N2 - 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.

AB - 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.

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