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Plasma FGF-19 Levels are Increased in Patients with Post-Bariatric Hypoglycemia

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  • Christopher M Mulla
  • Allison B Goldfine
  • Jonathan M Dreyfuss
  • Sander Houten
  • Hui Pan
  • David M Pober
  • Nicolai J Wewer Albrechtsen
  • Maria S Svane
  • Julie B Schmidt
  • Jens Juul Holst
  • Colleen M Craig
  • Tracey L McLaughlin
  • Mary-Elizabeth Patti
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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, 1094 ± 141 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.

Original languageEnglish
JournalObesity Surgery
Volume29
Issue number7
Pages (from-to)2092-2099
Number of pages8
ISSN0960-8923
DOIs
Publication statusPublished - Jul 2019

    Research areas

  • Bile acids, FGF-19, Gastric bypass, Hypoglycemia

ID: 56976952