Plasma FGF-19 Levels are Increased in Patients with Post-Bariatric Hypoglycemia
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Plasma FGF-19 Levels are Increased in Patients with Post-Bariatric Hypoglycemia. / Mulla, Christopher M.; Goldfine, Allison B.; Dreyfuss, Jonathan M.; Houten, Sander; Pan, Hui; Pober, David M.; Albrechtsen, Nicolai J. Wewer; Svane, Maria S.; Schmidt, Julie B.; Holst, Jens Juul; Craig, Colleen M.; McLaughlin, Tracey L.; Patti, Mary-Elizabeth.
In: Obesity Surgery, Vol. 29, No. 7, 2019, p. 2092-2099.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Plasma FGF-19 Levels are Increased in Patients with Post-Bariatric Hypoglycemia
AU - Mulla, Christopher M.
AU - Goldfine, Allison B.
AU - Dreyfuss, Jonathan M.
AU - Houten, Sander
AU - Pan, Hui
AU - Pober, David M.
AU - Albrechtsen, Nicolai J. Wewer
AU - Svane, Maria S.
AU - Schmidt, Julie B.
AU - Holst, Jens Juul
AU - Craig, Colleen M.
AU - McLaughlin, Tracey L.
AU - Patti, Mary-Elizabeth
PY - 2019
Y1 - 2019
N2 - Background Hypoglycemia is an increasingly recognized complication of bariatric surgery. Mechanisms contributing to glucose lowering remain incompletely understood. We aimed to identify differentially abundant plasma proteins in patients with post-bariatric hypoglycemia (PBH) after Roux-en-Y gastric bypass (RYGB), compared to asymptomatic post-RYGB. Methods Proteomic analysis of blood samples collected after overnight fast and mixed meal challenge in individuals with PBH, asymptomatic RYGB, severe obesity, or overweight recruited from outpatient hypoglycemia or bariatric clinics. Results The top-ranking differentially abundant protein at 120 min after mixed meal was fibroblast growth factor 19 (FGF-19), an intestinally derived hormone regulated by bile acid-FXR signaling; levels were 2.4-fold higher in PBH vs. asymptomatic post-RYGB (mean +/- SEM, 1094141 vs. 428 +/- 45, P < 0.001, FDR < 0.01). FGF-19 ELISA confirmed 3.5-fold higher concentrations in PBH versus asymptomatic (360 +/- 70 vs. 103 +/- 18, P = 0.025). To explore potential links between increased FGF-19 and GLP-1, residual samples from other human studies in which GLP-1 was modulated were assayed. FGF-19 levels did not change in response to infusion of GLP-1 and PYY in overweight/obese individuals. Infusion of the GLP-1 receptor antagonist exendin 9-39 in recently operated asymptomatic post-RYGB did not alter FGF-19 levels after mixed meal. By contrast, GLP-1 receptor antagonist infusion yielded a significant increase in FGF-19 levels after oral glucose in individuals with PBH. While plasma bile acids did not differ between PBH and asymptomatic post-RYGB, these data suggest unique interrelationships between GLP-1 and FGF-19 in PBH. Conclusions Taken together, these data support FGF-19 as a potential contributor to insulin-independent pathways driving postprandial hypoglycemia in PBH.
AB - Background Hypoglycemia is an increasingly recognized complication of bariatric surgery. Mechanisms contributing to glucose lowering remain incompletely understood. We aimed to identify differentially abundant plasma proteins in patients with post-bariatric hypoglycemia (PBH) after Roux-en-Y gastric bypass (RYGB), compared to asymptomatic post-RYGB. Methods Proteomic analysis of blood samples collected after overnight fast and mixed meal challenge in individuals with PBH, asymptomatic RYGB, severe obesity, or overweight recruited from outpatient hypoglycemia or bariatric clinics. Results The top-ranking differentially abundant protein at 120 min after mixed meal was fibroblast growth factor 19 (FGF-19), an intestinally derived hormone regulated by bile acid-FXR signaling; levels were 2.4-fold higher in PBH vs. asymptomatic post-RYGB (mean +/- SEM, 1094141 vs. 428 +/- 45, P < 0.001, FDR < 0.01). FGF-19 ELISA confirmed 3.5-fold higher concentrations in PBH versus asymptomatic (360 +/- 70 vs. 103 +/- 18, P = 0.025). To explore potential links between increased FGF-19 and GLP-1, residual samples from other human studies in which GLP-1 was modulated were assayed. FGF-19 levels did not change in response to infusion of GLP-1 and PYY in overweight/obese individuals. Infusion of the GLP-1 receptor antagonist exendin 9-39 in recently operated asymptomatic post-RYGB did not alter FGF-19 levels after mixed meal. By contrast, GLP-1 receptor antagonist infusion yielded a significant increase in FGF-19 levels after oral glucose in individuals with PBH. While plasma bile acids did not differ between PBH and asymptomatic post-RYGB, these data suggest unique interrelationships between GLP-1 and FGF-19 in PBH. Conclusions Taken together, these data support FGF-19 as a potential contributor to insulin-independent pathways driving postprandial hypoglycemia in PBH.
KW - Gastric bypass
KW - Hypoglycemia
KW - FGF-19
KW - Bile acids
U2 - 10.1007/s11695-019-03845-0
DO - 10.1007/s11695-019-03845-0
M3 - Journal article
C2 - 30976983
VL - 29
SP - 2092
EP - 2099
JO - Obesity Surgery
JF - Obesity Surgery
SN - 0960-8923
IS - 7
ER -
ID: 226791238