Objective Roux-en-Y gastric bypass (RYGB) is an effective way to induce sustainable weight loss and can be complicated by postprandial hyperinsulinaemic hypoglycaemia (PHH). To study the prevalence and the mechanisms behind the occurrence of hypoglycaemia after a mixed meal tolerance test (MMTT) in patients with primary RYGB. Design This is a cross-sectional study of patients 4 years after primary RYGB. Methods From a total population of 550 patients, a random sample of 44 patients completed the total test procedures. A standardized mixed meal was used as stimulus. Venous blood samples were collected at baseline, every 10 min during the first half hour and every 30 min until 210 min after the start. Symptoms were assessed by questionnaires. Hypoglycaemia is defined as a blood glucose level below 3.3 mmol/L. Results The prevalence of postprandial hypoglycaemia was 48% and was asymptomatic in all patients. Development of hypoglycaemia was more frequent in patients with lower weight at surgery (P = 0.045), with higher weight loss after surgery (P = 0.011), and with higher insulin sensitivity calculated by the homeostasis model assessment indexes (HOMA2-IR, P = 0.014) and enhanced beta cell function (insulinogenic index at 20 min, P = 0.001). Conclusion In a randomly selected population 4 years after primary RYGB surgery, 48% of patients developed a hypoglycaemic event during an MMTT without symptoms, suggesting the presence of hypoglycaemia unawareness in these patients. The findings in this study suggest that the pathophysiology of PHH is multifactorial.

Background/objectives Bile acids (BA) act as detergents in intestinal fat absorption and as modulators of metabolic processes via activation of receptors such as FXR and TGR5. Elevated plasma BA as well as increased intestinal BA signalling to promote GLP-1 release have been implicated in beneficial health effects of Roux-en-Y gastric bypass surgery (RYGB). Whether BA also contribute to the postprandial hypoglycaemia that is frequently observed post-RYGB is unknown. Methods Plasma BA, fibroblast growth factor 19 (FGF19), 7α-hydroxy-4-cholesten-3-one (C4), GLP-1, insulin and glucose levels were determined during 3.5 h mixed-meal tolerance tests (MMTT) in subjects after RYGB, either with (RYGB, n = 11) or without a functioning gallbladder due to cholecystectomy (RYGB-CC, n = 11). Basal values were compared to those of age, BMI and sex-matched obese controls without RYGB (n = 22). Results Fasting BA as well as FGF19 levels were elevated in RYGB and RYGB-CC subjects compared to non-bariatric controls, without significant differences between RYGB and RYGB-CC. Postprandial hypoglycaemia was observed in 8/11 RYGB-CC and only in 3/11 RYGB. Subjects who developed hypoglycaemia showed higher postprandial BA levels coinciding with augmented GLP-1 and insulin responses during the MMTT. The nadir of plasma glucose concentrations after meals showed a negative relationship with postprandial BA peaks. Plasma C4 was lower during MMTT in subjects experiencing hypoglycaemia, indicating lower hepatic BA synthesis. Computer simulations revealed that altered intestinal transit underlies the occurrence of exaggerated postprandial BA responses in hypoglycaemic subjects. Conclusion Altered BA kinetics upon ingestion of a meal, as frequently observed in RYGB-CC subjects, appear to contribute to postprandial hypoglycaemia by stimulating intestinal GLP-1 release.

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Background: Dumping syndrome (DS) and postbariatric hypoglycemia (PBH) are frequent complications of bariatric surgery. Bile acids (BA) have been implicated in their pathogenesis because both bariatric surgery and cholecystectomy (CCx) are known to modulate human BA metabolism. Objectives: Our investigation aimed to compare the prevalence of self-reported complaints of DS and PBH in postbariatric patients with and without CCx. Setting: A large peripheral hospital in the Netherlands. Methods: All patients who underwent bariatric surgery in 2008-2011 received standardized questionnaires on DS/PBH complaints. The relative risk (RR) of CCx was calculated as the risk of perceived DS and PBH in patients with and without CCx.Results: Of 590 participants, 146 (25%) had CCx before assessment of DS/PBH complaints. Participants were mostly female (82%) with median age of 46 years (interquartile range, 39-53). The RR for DS after CCx was higher in patients with body mass index ,30 kg/m 2 at the study (RR, 1.59; 95% CI, 1.04-2.42; P 5 .007) and in primary Roux-and-Y gastric bypass surgery patients (RR, 1.63; 95% CI, 1.10-2.42; P 5.018). Detailed analysis of the latter group associated women, age younger than 50 years, without diabetes and (most prominently) with excess weight loss 70% (RR, 2.73; 95% CI, 1.57-4.77; P 5 .0004) with greater risk of DS. The RR for PBH was higher after CCx in sleeve gastrectomy patients (RR, 4.5; 95% CI, 1.00-20.3; P 5 .036). Conclusion: High suspicion of DS and PBH after CCx is increased after bariatric surgery in certain subgroups, suggesting involvement of altered BA metabolism in their pathophysiology.