title: Increased levels of Dickkopf-1 are indicative of Wnt/β-catenin downregulation and lower osteoblast signaling in children and adolescents with type 1 diabetes mellitus, contributing to lower bone mineral density.
abstract: Higher levels of Dickkopf-1, which is an inhibitor of Wnt/β-catenin bone metabolic pathway, could be indicative of downregulated Wnt system, with possible lower osteoblast activation and higher osteoclast signaling in type 1 diabetes mellitus children and adolescents. Dickkopf-1 could significantly contribute to diabetes osteopathy.
  
  
  
  Increased fracture risk and elevated Dickkopf-1 levels, which is an inhibitor of Wnt/β-catenin bone metabolic pathway, have been documented in adult patients with type 2 diabetes mellitus (T2D), while no relevant data exist on childhood type 1 diabetes (T1D). Our aim was to study plasma Dickkopf-1 distribution in children and adolescents with T1D and to correlate Dickkopf-1 with metabolic bone markers and bone mineral density (BMD).
  
  
  
  We evaluated 40 children and adolescents with T1D (mean ± SD age 13.04 ± 3.53 years, T1D duration 5.15 ± 3.33 years) and 40 healthy age-matched and gender-matched controls (age 12.99 ± 3.3 years). Dickkopf-1 and bone metabolic markers were measured, while total body and lumbar spine BMD were evaluated with dual-energy X-ray absorptiometry (DXA).
  
  
  
  Dickkopf-1 demonstrated a Gaussian distribution, with higher levels in T1D patients (13.56 ± 5.34 vs 11.35 ± 3.76 pmol/L, p = 0.024). Higher values were found in boys and in prepubertal children. Dickkopf-1 correlated positively with osteoprotegerin and fasting glucose in patients, while positive correlation with sclerostin and total soluble receptor activator of nuclear factor-kappaB ligand (s-RANKL) was found in controls. Positive correlations with C-telopeptide cross-links (CTX), osteocalcin, alkaline phosphatase, phosphate, and insulin-like growth factor 1 (IGF1) were documented in both groups. Lumbar spine Z-score was positively associated with Dickkopf-1 in controls, while a negative trend was found in patients.
  
  
  
  Higher levels of Dickkopf-1 could indicate a downregulated Wnt/β-catenin system with possible lower osteoblast activation and higher osteoclast signaling in T1D children and adolescents. Dickkopf-1 could possibly be a significant contributor of T1D osteopathy. Future therapies could focus on Wnt/β-catenin metabolic pathway.
authors.affiliation: Diabetes Clinic, 2nd Department of Pediatrics, Athens University Medical School, "P&A Kyriakou" Children's Hospital, Thivon & Livadias, 11527 Ampelokipi, Athens, Greece. tsentidis@yahoo.gr.
authors.forename: C
authors.identifier: http://orcid.org/0000-0002-7803-5794
authors.initials: C
authors.lastname: Tsentidis
authors.affiliation: Laboratory of Clinical Biochemistry-Molecular Diagnostics, 2nd Department of Pediatrics, Athens University Medical School, "P & A Kyriakou" Children's Hospital, Athens, Greece.
authors.forename: D
authors.initials: D
authors.lastname: Gourgiotis
authors.affiliation: Diabetes Clinic, 2nd Department of Pediatrics, Athens University Medical School, "P&A Kyriakou" Children's Hospital, Thivon & Livadias, 11527 Ampelokipi, Athens, Greece.
authors.forename: L
authors.initials: L
authors.lastname: Kossiva
authors.affiliation: Laboratory of Clinical Biochemistry-Molecular Diagnostics, 2nd Department of Pediatrics, Athens University Medical School, "P & A Kyriakou" Children's Hospital, Athens, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Marmarinos
authors.affiliation: Department of Bone and Mineral Metabolism, Institute of Child Health, "Aghia Sophia" Children's Hospital, Athens, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Doulgeraki
authors.affiliation: Diabetes Clinic, 2nd Department of Pediatrics, Athens University Medical School, "P&A Kyriakou" Children's Hospital, Thivon & Livadias, 11527 Ampelokipi, Athens, Greece.
authors.forename: K
authors.initials: K
authors.lastname: Karavanaki
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D015519:Bone Density / Q000502:physiology; D019485:Bone Morphogenetic Proteins / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D015536:Down-Regulation / Q000502:physiology*; D005260:Female; D005819:Genetic Markers; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008297:Male; D010006:Osteoblasts / Q000378:metabolism; D010024:Osteoporosis / Q000097:blood* / Q000209:etiology / Q000503:physiopathology; D011627:Puberty / Q000502:physiology; D012727:Sex Characteristics; D060449:Wnt Signaling Pathway / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D001786:Blood Glucose; D019485:Bone Morphogenetic Proteins; C501126:DKK1 protein, human; D005819:Genetic Markers; D036341:Intercellular Signaling Peptides and Proteins; C422903:SOST protein, human
keywords: Adolescents; Bone metabolism; Children; Dickkopf-1; Osteoporosis; Type 1 diabetes