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Separate and Combined Effects of GIP and GLP-1 Infusions on Bone Metabolism in Overweight Men without Diabetes

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  • Natasha Chidekel Bergmann
  • Asger Lund
  • Lærke Smidt Gasbjerg
  • Niklas Rye Jørgensen
  • Lene Jessen
  • Bolette Hartmann
  • Jens Juul Holst
  • Mikkel Bring Christensen
  • Tina Vilsbøll
  • Filip Krag Knop
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CONTEXT: The gut-derived incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) have been suggested to play a role in bone metabolism. Exogenous administration of GIP inhibits bone resorption, but the effect of GLP-1 is less clear. Furthermore, the combined effect of exogenous GIP and GLP-1 on bone metabolism is unknown.

OBJECTIVE: To investigate the effect of separate and combined infusions of the incretin hormones GIP and GLP-1 on bone resorption and formation.

DESIGN: Randomized, double-blinded, placebo-controlled, crossover study including five study days.

PARTICIPANTS: Seventeen overweight/obese men.

INTERVENTIONS: On the first study day, a 50-g oral glucose tolerance test (OGTT) was performed. On the next four study days, isoglycemic IV glucose infusions (IIGI), mimicking the glucose excursions from the OGTT, were performed with concomitant infusions of GIP (4 pmol/kg/min), GLP-1 (1 pmol/kg/min), GIP+GLP-1 (4 and 1 pmol/kg/min, respectively), or placebo, respectively.

PRIMARY OUTCOMES: Changes in bone resorption assessed by measurements of carboxy-terminal type I collagen crosslinks (CTX) and in bone formation as assessed by procollagen type 1 N-terminal propeptide (P1NP) concentrations.

RESULTS: During the OGTT, CTX was significantly lowered by 54 ± 13% from baseline (mean ± SD) compared with 28 ± 12% during IIGI + saline (P < 0.0001). During IIGI+GLP-1 and IIGI+GIP, CTX was lowered by 65 ± 16% and 74 ± 9%, respectively, from baseline, whereas IGII+GIP+GLP-1 lowered CTX by 84 ± 4% from baseline. P1NP levels were unaffected by the interventions.

CONCLUSIONS: Our data suggest that GLP-1, like GIP, may be involved in regulation of bone resorption and that GIP and GLP-1 together have partially additive inhibitory effects.

OriginalsprogEngelsk
Artikelnummerjcem_201900008
TidsskriftThe Journal of clinical endocrinology and metabolism
Vol/bind104
Udgave nummer7
Sider (fra-til)2953-2960
Antal sider8
ISSN0021-972X
DOI
StatusUdgivet - jul. 2019

Bibliografisk note

Copyright © 2019 Endocrine Society.

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