Proglucagon peptide secretion profiles in type 2 diabetes before and after bariatric surgery: 1-year prospective study
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Proglucagon peptide secretion profiles in type 2 diabetes before and after bariatric surgery : 1-year prospective study. / Alexiadou, Kleopatra; Cuenco, Joyceline; Howard, James; Wewer Albrechtsen, Nicolai Jacob; Ilesanmi, Ibiyemi; Kamocka, Anna; Tharakan, George; Behary, Preeshila; Bech, Paul R.; Ahmed, Ahmed R.; Purkayastha, Sanjay; Wheller, Robert; Fleuret, Matthieu; Holst, Jens Juul; Bloom, Stephen R.; Khoo, Bernard; Tan, Tricia M.M.
I: B M J Open Diabetes Research & Care, Bind 8, Nr. 1, e001076, 2020.Publikation: Bidrag til tidsskrift › Review › Forskning › fagfællebedømt
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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 -
ID: 244572991