TY - JOUR
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.
UR - http://www.scopus.com/inward/record.url?scp=79955387227&partnerID=8YFLogxK
U2 - 10.1126/scitranslmed.3002043
DO - 10.1126/scitranslmed.3002043
M3 - Article
C2 - 21525399
AN - SCOPUS:79955387227
SN - 1946-6234
VL - 3
JO - Science Translational Medicine
JF - Science Translational Medicine
IS - 80
M1 - 80re2
ER -
