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Postprandial Metabolite Profiles Reveal Differential Nutrient Handling After Bariatric Surgery Compared With Matched Caloric Restriction

Khoo, Chin Meng MBBS, MRCP, FAMS, MD*,†; Muehlbauer, Michael J.*; Stevens, Robert D. PhD*,‡; Pamuklar, Zehra MD, PhD§; Chen, Jiegen PhD§; Newgard, Christopher B. PhD*,‡,¶; Torquati, Alfonso MD, MSCI*,§

doi: 10.1097/SLA.0b013e318296633f
Original Articles

Background: Roux-en-Y gastric bypass (RYGB) surgery results in exaggerated postprandial insulin and incretin responses and increased susceptibility to hypoglycemia.

Objective: We examined whether these features are due to caloric restriction (CR) or altered nutrient handling.

Methods: We 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.

Results: Two 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.

Conclusions: RYGB 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.

Supplemental Digital Content is Available in the Text.Metabolic flexibility (ie, greater disposal of glucose and amino acids (AAs) and more complete β-oxidation of fatty acids) was observed in the early period after Roux-en-Y gastric bypass (RYGB) surgery compared with caloric restriction. Furthermore, changes in the availability of AAs and several of gluconeogenic substrates might explain the enigma of exaggerated postprandial insulin and incretin secretion and the propensity to hypoglycemia, respectively, after RYGB surgery.

*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.

Reprints: Alfonso Torquati, MD, MSCI, Department of Surgery & Sarah W. Stedman Nutrition and Metabolism Center, DUMC 3351, Duke University Medical Center, Durham, NC 27713. E-mail:

Supported by National Institute of Health grants K23DK075907 (to A.T.) and PO1DK058398 (to C.B.N.) and a SAGES Research Grant Award.

Disclosure: The authors declare that there is no duality of interest associated with this article.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (

© 2014 by Lippincott Williams & Wilkins.