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Glucose-Dependent Insulinotropic Polypeptide (GIP) Inhibits Bone Resorption independently of Insulin and Glycemia

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DOI

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

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

    Research output: Contribution to journalJournal articleResearchpeer-review

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  • Mikkel B Christensen
  • Asger Lund
  • Salvatore Calanna
  • Niklas R Jørgensen
  • Jens J Holst
  • Tina Vilsbøll
  • Filip K Knop
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Context: The gut hormone GIP causes postprandial insulin release and inhibits bone resorption assessed by carboxy-terminal collagen crosslinks (CTX).

Objective: To clarify if GIP affects biomarkers involved in bone homeostasis independently of insulin release and glycemic level.

Design: Randomized, double-blinded, cross-over study with 5 study days.

Patients: Ten lean male C-peptide-negative patients with type 1 diabetes.

Interventions: On 3 matched days with 'low glycemia' (i.e. plasma glucose clamped between 3-7 mmol/L for 120 minutes) we administered (IV) either GIP (4 pmol/kg/min), glucagon-like-peptide-1 (GLP-1) (1 pmol/kg/min) or placebo (saline); and on 2 matched days with 'high glycemia' (i.e. clamped at 12 mmol/L for 90 minutes) we administered (IV) either GIP (4 pmol/kg/min) or saline.

Main Outcome Measures: CTX, N-terminal propeptide of type 1 procollagen (P1NP), and PTH.

Results: During 'low glycemia': GIP progressively suppressed CTX from baseline by up to 59±18% compared to 24±10% during saline infusion (P<0.0001). Absolute values of P1NP and PTH did not differ between GIP and placebo days. During 'high glycemia': GIP suppressed CTX from baseline by up to 59±19% compared to 7±9% during saline infusion (P<0.0001). P1NP did not differ between GIP and placebo days. GIP suppressed PTH after 60 minutes compared to saline (P<0.01), but this difference disappeared after 90 minutes.

Conclusions: Short term GIP infusions robustly reduces bone resorption independently of endogenous insulin secretion and during both elevated and low plasma glucose levels, but has no effect on P1NP or PTH after 90 minutes.

Original languageEnglish
JournalThe Journal of clinical endocrinology and metabolism
Volume103
Issue number1
Pages (from-to)288-294
Number of pages7
ISSN0021-972X
DOIs
Publication statusPublished - 2018

    Research areas

  • Journal Article

ID: 51975650