Natasha Chidekel Bergmann1,2,3, Asger Lund1,4, Lærke Smidt Gasbjerg1,3,5, Niklas Rye Jørgensen6,7, Lene Jessen2, Bolette Hartmann3,5, Jens Juul Holst3,5, Mikkel Bring Christensen1,8,9, Tina Vilsbøll1,8, Filip Krag Knop1,5,8. 1. Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen, Gentofte Hospital, Hellerup, Denmark. 2. Department of In Vivo Pharmacology, Zealand Pharma A/S, Glostrup, Denmark. 3. Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. 4. Department of Medicine, Gentofte Hospital, Hellerup, Denmark. 5. Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. 6. Department of Clinical Chemistry, Rigshospitalet, University of Copenhagen, Glostrup, Denmark. 7. OPEN, Odense University Hospital, Odense, Denmark. 8. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. 9. Department of Clinical Pharmacology, Bispebjerg Hospital, Copenhagen, Denmark.
Abstract
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 typeI 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.
RCT Entities:
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/obesemen. 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.
Authors: Peter Lindquist; Lærke Smidt Gasbjerg; Jacek Mokrosinski; Jens Juul Holst; Alexander Sebastian Hauser; Mette Marie Rosenkilde Journal: Front Endocrinol (Lausanne) Date: 2022-06-29 Impact factor: 6.055