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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

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Abstract

Summary

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.

Introduction

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).

Methods

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).

Results

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.

Conclusions

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.

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Authors and Affiliations

  1. Diabetes Clinic, 2nd Department of Pediatrics, Athens University Medical School, “P&A Kyriakou” Children’s Hospital, Thivon & Livadias, 11527 Ampelokipi, Athens, Greece

    C. Tsentidis, L. Kossiva & K. Karavanaki

  2. Laboratory of Clinical Biochemistry-Molecular Diagnostics, 2nd Department of Pediatrics, Athens University Medical School, “P & A Kyriakou” Children’s Hospital, Athens, Greece

    D. Gourgiotis & A. Marmarinos

  3. Department of Bone and Mineral Metabolism, Institute of Child Health, “Aghia Sophia” Children’s Hospital, Athens, Greece

    A. Doulgeraki

Authors
  1. C. Tsentidis
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  2. D. Gourgiotis
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  3. L. Kossiva
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  4. A. Marmarinos
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  5. A. Doulgeraki
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  6. K. Karavanaki
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Correspondence to C. Tsentidis.

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Tsentidis, C., Gourgiotis, D., Kossiva, L. et al. 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. Osteoporos Int 28, 945–953 (2017). https://doi.org/10.1007/s00198-016-3802-5

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