Proglucagon peptide secretion profiles in type 2 diabetes before and after bariatric surgery: 1-year prospective study

Abstract

IntroductionHyperglucagonemia is a key pathophysiological driver of type 2 diabetes. Although Roux-en-Y gastric bypass (RYGB) is a highly effective treatment for diabetes, it is presently unclear how surgery alters glucagon physiology. The aim of this study was to characterize the behavior of proglucagon-derived peptide (glucagon, glucagon-like peptide-1 (GLP-1), oxyntomodulin, glicentin) secretion after RYGB surgery.Research design and methodsProspective study of 19 patients with obesity and pre-diabetes/diabetes undergoing RYGB. We assessed the glucose, insulin, GLP-1, glucose-dependent insulinotropic peptide (GIP), oxyntomodulin, glicentin and glucagon responses to a mixed-meal test (MMT) before and 1, 3 and 12 months after surgery. Glucagon was measured using a Mercodia glucagon ELISA using the ‘Alternative’ improved specificity protocol, which was validated against a reference liquid chromatography combined with mass spectrometry method.ResultsAfter RYGB, there were early improvements in fasting glucose and glucose tolerance and the insulin response to MMT was accelerated and amplified, in parallel to significant increases in postprandial GLP-1, oxyntomodulin and glicentin secretion. There was a significant decrease in fasting glucagon levels at the later time points of 3 and 12 months after surgery. Glucagon was secreted in response to the MMT preoperatively and postoperatively in all patients and there was no significant change in this postprandial secretion. There was no significant change in GIP secretion.ConclusionsThere is a clear difference in the dynamics of secretion of proglucagon peptides after RYGB. The reduction in fasting glucagon secretion may be one of the mechanisms driving later improvements in glycemia after RYGB.Trial registration numberNCT01945840.

Do Gut Hormones Contribute to Weight Loss and Glycaemic Outcomes after Bariatric Surgery?

“…The changes in postprandial levels of GIP after RYGB and SG are inconsistent [33,48,83,[97][98][99][100][101] (Table 1). On the other hand, GIP levels after AGB appear unchanged [33,56,[102][103][104] (Table 1).…”

“…Exogenous administration of OXM reduces food intake and increases energy expenditure in humans [117,118]. Few studies have assessed the changes in oxyntomodulin levels after bariatric surgery [23,33,97,119] and their results are presented in Table 1.…”

“…Currently, there is no known glicentin receptor in humans. Limited data is also available on the changes of glicentin levels after bariatric surgery [23,33,97], however postprandial glicentin levels appear to be elevated after RYGB (Table 1).…”

Roux-en-Y Gastric Bypass Increases Glycemic Variability and Time in Hypoglycemia in Patients With Obesity and Prediabetes or Type 2 Diabetes: A Prospective Cohort Study

“…No participant during this study reported any symptoms, nor were admitted for treatment of hypoglycaemia. Table 2 show that there were post-surgical enhancements in post-prandial GLP-1 and a reduction of glucagon secretion during the MMT paralleling the improvement in glucose tolerance (14). We hypothesised that the following parameters remained significantly associated with %TIR<3.9 (p=0.0129 and 0.003 respectively).…”

Methods and Guidelines for Measurement of Glucagon in Plasma

“…However, it was also clear that the alternative protocol was associated with systematically lower readings suggesting that analyte had been lost by this procedure. This was in particular the case for protein-induced secretion of glucagon which was completely lost [55].…”