The Journal of Clinical Endocrinology and Metabolism Journal Article

Effects of Exogenous GIP and GLP-2 on Bone Turnover in Individuals With Type 2 Diabetes

July 09, 2024
 

Kirsa Skov-Jeppesen, Charlotte B Christiansen, Laura S Hansen, Johanne A Windeløv, Nora Hedbäck, Lærke S Gasbjerg, Morten Hindsø, Maria S Svane, Sten Madsbad, Jens J Holst, Mette M Rosenkilde, Bolette Hartmann
The Journal of Clinical Endocrinology & Metabolism, Volume 109, Issue 7, July 2024, Pages 1773–1780
https://doi.org/10.1210/clinem/dgae022

Abstract

Context

Individuals with type 2 diabetes (T2D) have an increased risk of bone fractures despite normal or increased bone mineral density. The underlying causes are not well understood but may include disturbances in the gut-bone axis, in which both glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-2 (GLP-2) are regulators of bone turnover. Thus, in healthy fasting participants, both exogenous GIP and GLP-2 acutely reduce bone resorption.

Objective

The objective of this study was to investigate the acute effects of subcutaneously administered GIP and GLP-2 on bone turnover in individuals with T2D.

Methods

We included 10 men with T2D. Participants met fasting in the morning on 3 separate test days and were injected subcutaneously with GIP, GLP-2, or placebo in a randomized crossover design. Blood samples were drawn at baseline and regularly after injections. Bone turnover was estimated by circulating levels of collagen type 1 C-terminal telopeptide (CTX), procollagen type 1 N-terminal propeptide (P1NP), sclerostin, and PTH.

Results

GIP and GLP-2 significantly reduced CTX to (mean ± SEM) 66 ± 7.8% and 74 ± 5.9% of baseline, respectively, compared with after placebo (P = .001). In addition, P1NP and sclerostin increased acutely after GIP whereas a decrease in P1NP was seen after GLP-2. PTH levels decreased to 67 ± 2.5% of baseline after GLP-2 and to only 86 ± 3.4% after GIP.

Conclusion

Subcutaneous GIP and GLP-2 affect CTX and P1NP in individuals with T2D to the same extent as previously demonstrated in healthy individuals.

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