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

Abstract

Background Roux-en-Y gastric bypass (RYGB) surgery results in exaggerated postprandial insulin and incretin responses, and increased susceptibility to hypoglycemia. 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 challenge test (MMT) in twenty morbidly obese subjects with type 2 diabetes who underwent RYGB surgery or matched CR. Acylcarnitines and amino acids was measured using targeted mass spectrometry. 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, GIP and GLP-1), glucose, and multiple amino acids, including branched-chain and aromatic species, exhibited a more rapid rate of appearance and clearance in RYGB subjects compared to CR during the MMT. In the RYGB group, changes in leucine/isoleucine, methionine, phenylalanine and GLP-1 responses were associated with changes in insulin response. Levels of alanine, pyruvate, and lactate decreased significantly at the later stages of meal challenge in RYGB subjects, but increased with CR. Conclusions RYGB surgery results in improved metabolic flexibility (i.e. greater disposal of glucose and amino acids, and more complete β-oxidation of fatty acids) compared to CR. The changes in the amino acid 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 subjects.

Accelerated protein digestion and amino acid absorption after Roux-en-Y gastric bypass

“…A lower splanchnic extraction of the amino acids may contribute but is likely secondary to the accelerated amino acid absorption after RYGB (13,(16)(17)(18). Furthermore, our results confirm that the postprandial increases in plasma amino acids observed in previous RYGB studies (19,20) result from accelerated appearance of amino acids from orally ingested protein and not from increased endogenous release.…”

Neuroendocrine adaptations to bariatric surgery

“…The reduction in BCAA following RYGB is associated with increased disposal of circulating amino acids and glucose, and more complete fatty acid beta oxidation. While this may improve glucose homeostasis it may well increase susceptibility to hypoglycaemia (Khoo et al, 2014). The role, if any, of BCAAs in the mechanism of action of bariatric surgery is unclear.…”

Pancreatic hyperplasia after gastric bypass surgery in a GK rat model of non-obese type 2 diabetes

“…A major challenge in reversing the progressive deterioration of glycemic control over time in T2DM is to increase b-cell mass and promote b-cell function to fulfill the unmet need for insulin. Gastric bypass surgery has been shown to reverse T2DM or block disease progression, leading to diabetes remission in many morbidly obese patients (Pories et al 1995, Hickey et al 1998, Schauer et al 2003, Khoo et al 2014. In the present study, gastric bypass surgery in a non-obese diabetic rodent (GK rat) model led to significant improvement in postprandial hyperglycemia, plasma c-peptide level and first-phase insulin secretion, normalization of islet structure, and increase of b-cell mass with proportional increase of non-b endocrine cells and pancreas tissue hyperplasia.…”

“…Bariatric surgery is often used to treat morbid obesity (BMI O39), and has a notable effect in resolving T2DM in these obese patients (Pories et al 1995, Schauer et al 2003, Khoo et al 2014. Roux-en-Y gastric bypass (RYGB), the most common type of bariatric surgery, converts w82% of diabetic obese patients and 100% of prediabetic obese patients to normal status (Schauer et al 2000, Wittgrove & Clark 2000.…”