title: Differential impact of glucose administered intravenously or orally on bone turnover markers in healthy male subjects.
abstract: Patients with type-1 (T1D) and type-2 diabetes mellitus (T2D) have an increased risk of hip fracture. The underlying mechanisms may involve disturbances in the incretin hormones. Our aim was to clarify if glucose administration i.e. orally or intravenously differentially affects bone turnover markers in healthy males.
  
  
  
  12 healthy males were included in a cross-over study consisting of three tests following an 8hour fast. First, an oral glucose tolerance test (OGTT) was performed. Subsequently, we carried out an isoglycemic intravenous glucose infusion (IIGI) that closely mimicked the glucose response curve to the oral glucose load. We analyzed blood samples for the bone turnover markers serum C-terminal telopeptide of type I collagen (s-CTX) and serum procollagen type I N propeptide (s-P1NP), as well as insulin, glucose, gastric inhibitory peptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2). Finally, eight of the twelve participants underwent a control experiment where they fasted for 3h (Control).
  
  
  
  While OGTT induced a 50% reduction in s-CTX, only a ~30% reduction was seen during the IIGI and the Control. Neither intervention influenced s-P1NP. The concentration of insulin was highest during the OGTT. However, insulin was also increased significantly during the IIGI compared to the Control. Plasma concentrations of GIP, GLP-1 and GLP-2 were higher under the OGTT than during the IIGI and Control. A linear regression indicated that peak p-GIP significantly predicts nadir s-CTX (p=0.03), and that peak p-GIP could explain 34% of the variability in nadir s-CTX (adjusted R2=0.34).
  
  
  
  This study indicates that glucose per se does not acutely affect bone turnover markers. However, gastrointestinal hormones, especially GIP, possibly in combination with hyperglycemia, may have an acute, uncoupling effect on bone turnover leading to a decrease in bone resorption but no change in bone formation.
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark. Electronic address: sidsewestberg@gmail.com.
authors.forename: Sidse
authors.initials: S
authors.lastname: Westberg-Rasmussen
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Jakob
authors.initials: J
authors.lastname: Starup-Linde
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Kjeld
authors.initials: K
authors.lastname: Hermansen
authors.affiliation: Department of Biomedical Sciences and The NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jens Juul
authors.initials: JJ
authors.lastname: Holst
authors.affiliation: Department of Biomedical Sciences and The NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Bolette
authors.initials: B
authors.lastname: Hartmann
authors.affiliation: Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark; Clinical Institute, Aalborg University and University Hospital, Aalborg, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Vestergaard
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Gregersen
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D015415:Biomarkers / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D016723:Bone Remodeling / Q000187:drug effects*; D024042:Collagen Type I / Q000097:blood; D005768:Gastrointestinal Hormones / Q000378:metabolism; D005947:Glucose / Q000008:administration & dosage* / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D006262:Health; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood; D011347:Procollagen / Q000097:blood; D055815:Young Adult
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D024042:Collagen Type I; D005768:Gastrointestinal Hormones; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide; D005947:Glucose
keywords: Bone turnover markers (BTMs); C-terminal telopeptide of type I collagen (s-CTX); Gastric inhibitory peptide (GIP); Glucagon-like peptide-1 (GLP-1); Glucagon-like peptide-2 (GLP-2); Isoglycemic intravenous glucose infusion (IIGI); Oral glucose tolerance test (OGTT); Procollagen type I N propeptide (s-P1NP)