TY - JOUR

T1 - Proglucagon peptide secretion profiles in type 2 diabetes before and after bariatric surgery

T2 - 1-year prospective study

AU - Alexiadou, Kleopatra

AU - Cuenco, Joyceline

AU - Howard, James

AU - Wewer Albrechtsen, Nicolai Jacob

AU - Ilesanmi, Ibiyemi

AU - Kamocka, Anna

AU - Tharakan, George

AU - Behary, Preeshila

AU - Bech, Paul R.

AU - Ahmed, Ahmed R.

AU - Purkayastha, Sanjay

AU - Wheller, Robert

AU - Fleuret, Matthieu

AU - Holst, Jens Juul

AU - Bloom, Stephen R.

AU - Khoo, Bernard

AU - Tan, Tricia M.M.

PY - 2020

Y1 - 2020

N2 - Introduction Hyperglucagonemia 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 methods Prospective 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. Results After 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. Conclusions There 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 number NCT01945840.

AB - Introduction Hyperglucagonemia 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 methods Prospective 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. Results After 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. Conclusions There 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 number NCT01945840.

KW - bariatric surgery

KW - glucagon

KW - glucagon-like peptide-1 (GLP-1)

KW - obesity

UR - http://www.scopus.com/inward/record.url?scp=85082614463&partnerID=8YFLogxK

U2 - 10.1136/bmjdrc-2019-001076

DO - 10.1136/bmjdrc-2019-001076

M3 - Review

C2 - 32209584

AN - SCOPUS:85082614463

VL - 8

JO - B M J Open Diabetes Research & Care

JF - B M J Open Diabetes Research & Care

SN - 2052-4897

IS - 1

M1 - e001076

ER -