title: Differences in biochemical bone markers by diabetes type and the impact of glucose.
abstract: BACKGROUND
  Diabetes mellitus is associated with an increased fracture risk, however the fracture risk is 7 fold increased in patients with type 1 diabetes (T1D) and 1.4 fold increased in patients with type 2 diabetes (T2D) with decreased and increased bone mineral density, respectively. Oral ingestion of glucose causes an acute decrease in bone turnover markers, and thus glucose levels may affect bone turnover in diabetes.
  
  
  OBJECTIVE
  The aim was to examine disparities in bone turnover markers between patients with T1D and T2D and evaluate the effect of glucose on bone turnover.
  
  
  METHODS
  A cross-sectional study was conducted. Patients diagnosed with T1D (n=98) or T2D (n=96) were included from the outpatient clinics at two University Hospitals. All individuals had normal renal function. Glucose and bone turnover markers were measured in non-fasting blood samples.
  
  
  RESULTS
  P-procollagen type 1 amino terminal propeptide (P1NP), p-osteocalcin (OC), and s-Receptor Activator of Nuclear factor Kappa beta Ligand (RANKL) were lower in patients with T2D compared to T1D, and s-osteoprotegerin (OPG) was higher in T2D. P-C-terminal cross-linked telopeptide of type-I collagen (CTX), p-fibroblast growth factor-23 (FGF-23), p-sclerostin, and p-undercarboxylated osteocalcin (ucOC) were similar in between the two groups of patients. Increasing non-fasting glucose levels were inversely related to p-CTX, p-P1NP, p-OC, and p-ucOC and directly related to s-OPG in simple linear and multiple linear regressions adjusted for factors influencing bone turnover markers including HbA1c.
  
  
  CONCLUSIONS
  Bone turnover markers were lower in patients with T2D compared to T1D. Acute blood glucose alterations may change bone turnover mediated by OPG and have detrimental effects on bone health in diabetes.
  
  
  BACKGROUND
  ClinicalTrials.govNCT01870557.
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
authors.forename: Jakob
authors.initials: J
authors.lastname: Starup-Linde
authors.affiliation: Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Simon
authors.initials: S
authors.lastname: Lykkeboe
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Gregersen
authors.affiliation: Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Ellen-Margrethe
authors.initials: EM
authors.lastname: Hauge
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Bente Lomholt
authors.initials: BL
authors.lastname: Langdahl
authors.affiliation: Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Aase
authors.initials: A
authors.lastname: Handberg
authors.affiliation: Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Vestergaard
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood*; D001786:Blood Glucose / Q000378:metabolism*; D016723:Bone Remodeling; D001842:Bone and Bones / Q000378:metabolism*; D024042:Collagen Type I / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005215:Fasting / Q000097:blood; D005260:Female; D000089703:Fibroblast Growth Factor-23; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D053244:Osteoprotegerin / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood; D011347:Procollagen / Q000097:blood
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D024042:Collagen Type I; D000089703:Fibroblast Growth Factor-23; D006442:Glycated Hemoglobin; D015675:Osteocalcin; D053244:Osteoprotegerin; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C000717427:FGF23 protein, human; C506030:TNFRSF11B protein, human; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide
keywords: Bone turnover; Bone turnover markers; Diabetes mellitus; Glucose