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.