• Chin Meng Khoo, Michael J Muehlbauer, Robert D Stevens, Zehra Pamuklar, Jiegen Chen, Christopher B Newgard, and Alfonso Torquati.
• *Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC †Department of Medicine, National University Health System, Singapore and Departments of ‡Medicine §General Surgery ¶Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC.
• Ann. Surg. 2014 Apr 1; 259 (4): 687-93.

BackgroundRoux-en-Y gastric bypass (RYGB) surgery results in exaggerated postprandial insulin and incretin responses and increased susceptibility to hypoglycemia.ObjectiveWe examined whether these features are due to caloric restriction (CR) or altered nutrient handling.MethodsWe performed comprehensive analysis of postprandial metabolite responses during a 2-hour mixed-meal tolerance (MMT) test in 20 morbidly obese subjects with type 2 diabetes who underwent RYGB surgery or matched CR. Acylcarnitines and amino acids (AAs) were measured using targeted mass spectrometry. A linear mixed model was used to determine the main effect of interventions and interaction term to assess the effect of interventions on postprandial kinetics.ResultsTwo weeks after these interventions, several gut hormones (insulin, glucose-dependent insulinotropic polypeptide, and glucagon-like peptide 1), glucose, and multiple AAs, including branched-chain and aromatic species, exhibited a more rapid rate of appearance and clearance in RYGB surgery subjects than in CR subjects during the MMT test. In the RYGB surgery group, changes in leucine/isoleucine, methionine, phenylalanine, and glucagon-like peptide 1 response were associated with changes in insulin response. Levels of alanine, pyruvate, and lactate decreased significantly at the later stages of meal challenge in RYGB surgery subjects but increased with CR.ConclusionsRYGB surgery results in improved metabolic flexibility (ie, greater disposal of glucose and AAs and more complete β-oxidation of fatty acids) compared with CR. The changes in the AA kinetics may augment the hormonal responses seen after RYGB surgery. The reduction in key gluconeogenic substrates in the postprandial state may contribute to increased susceptibility to hypoglycemic symptoms in RYGB surgery subjects.

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