Chronically elevated basal GLP-1 mediates persistent nausea symptoms following weight reduction surgery

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 660-676-Clinical Obesity Treatment
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-674
Noora Alrasheid*1, Rosaire Gray2, Pratik Sufi3 and Elizabith Atherton3
1University College London, London, United Kingdom, 2NLOSS, Whittington Hospital, London, 3Whittington Health, London, United Kingdom
Background:  Gastric bypass successfully treats obesity and results in sustained weight loss and improved insulin sensitivity, benefits at least partly mediated by elevation in gut peptides, such as, glucagon-like peptide-1 (GLP-1).  However, a sub-set of patients experience severe and intolerable nausea and vomiting (N&V) that persists for beyond the initial 3 months following Roux-en-Y gastric bypass (RYGB) surgery.

Aim.  The aim of this study was to investigate whether: A) N&V symptoms are related to elevated GLP-1 levels, and, B) whether treatment to reduce systemic GLP-1 ameliorates these symptoms.  The study also aimed to ascertain whether GLP-1 is either, directly or indirectly, associated with leptin levels.

Methods.  Forty two female, non-diabetic subjects were studied in 5 groups.  Group (1): patients with N&V after RYGB surgery (n=10).  Group (2): patients with no symptoms after RYGB surgery (n=10).  Group (3): morbidly obese patients (n=7).  Group (4): obese/overweight subjects (n=6).  Group (5): lean healthy subjects (n=8).  Blood was collected in the fasting and post-prandial states.  Plasma concentrations of insulin, glucose, GLP-1 and adipokines were measured.  A sub-set of symptomatic patients were treated with Octreotide (somatostatin analogue) and GLP-1 measured. Subcutaneous (SC) and omental (OM) adipose tissue were collected from morbidly obese patients during bariatric surgery.  Adipose tissue was treated with recombinant GLP-1 for 16 hours and the media assayed for leptin.

Results.  Subjects with N&V post RYGB had significantly elevated fasting GLP-1 levels (p=0.03) compared to all other groups.  Weight loss, glucose, insulin, and GLP-1 responses to an 180Kcal meal were similar in subjects with and without N&V.  Patients treated with Octreotide showed reduced GLP-1 levels and improvements in their symptoms.  Fasting plasma leptin was significantly lower in subjects with N&V compared to those without (p=0.04) and leptin secretion from adipose explants was inhibited by GLP-1 treatment.

Conclusion.  The persistent N&V post RYGB surgery appears to be mediated by elevated fasting GLP-1 levels, as inhibition with Octreotide helps both lower GLP-1 and ameliorate symptoms.  However, potential detrimental effects on weight maintenance and insulin sensitivity need to be considered.  GLP-1 also has a direct inhibitory effect on leptin secretion, so decreased leptin levels early after RYGB might be explained by elevated GLP-1 levels.

Nothing to Disclose: NA, RG, PS, EA

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