ISSN 2632-9808 (online)

Obesity Abstracts (2020) 2 P8 | DOI: 10.1530/obabs.02.P8

Proglucagon peptide secretion post Roux-en-Y gastric bypass: one year prospective study

Kleopatra Alexiadou1, Joyceline Cuenco1, James Howard2, Nicolai Wewer Albrechtsen3,4, Ibeyimi Ilesanmi1, Anna Kamocka1, George Tharakan1, Preeshila Behary1, Ahmed R Ahmed5, Jens J Holst6, Stephen R Bloom1, Bernard Khoo7 & Tricia M Tan1

1Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK; 2LGC, Fordham, UK; 3Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark; 4NNF Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; 5Department of Surgery and Cancer, Imperial College Healthcare NHS Trust, London, UK; 6Panam Institute, Department of Biomedical Sciences and the NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark; 7UCL Division of Medicine, Royal Free Hospital, London, UK.

Background: Hyperglucagonaemia is one of the key players in the pathophysiology of type 2 diabetes. Roux-en-Y Gastric Bypass (RYGB) is currently a highly effective treatment for weight loss and diabetes remission. However, the role of glucagon in the above effects is unclear.

Aim: To characterise the behaviour of proglucagon-derived peptides (glucagon, glucagon-like peptide-1, oxyntomodulin, glicentin) after RYGB surgery.

Subjects and methods: We profiled prospectively nineteen patients with obesity and pre-diabetes/diabetes undergoing RYGB by assessing the glucose, insulin, glucagon-like peptide-1 (GLP-1), GIP, oxyntomodulin, glicentin and glucagon responses to a mixed-meal test (MMT) before and 1, 3 and 12 months post-surgery. Glucagon was measured using a Mercodia glucagon ELISA utilising the ‘Alternative’ improved specificity protocol, which was validated against a reference LC/MS-MS method.

Results: After RYGB, there were early improvements in fasting glucose and glucose tolerance accompanied by an accelerated and amplified insulin response to MMT, in parallel to significant increases in post-prandial GLP-1, oxyntomodulin and glicentin secretion. There was a significant decrease in fasting glucagon levels at 3 and 12 months post-surgery. Glucagon response to the MMT was decreased post-prandially at 3 and 12 months after surgery. There was no significant change in GIP secretion.

Conclusions: RYGB clearly alters the dynamics of secretion of proglucagon peptides. The reduction in fasting and post-prandial glucagon secretion may be one of the mechanisms driving later improvements in glycaemia after RYGB.