Diabetes Clinic, 2nd Department of Pediatrics, Athens University Medical School, "P&A Kyriakou" Children's Hospital, Thivon & Livadias, 11527 Ampelokipi, Athens, Greece.
Laboratory of Clinical Biochemistry-Molecular Diagnostics, 2nd Department of Pediatrics, Athens University Medical School, "P & A Kyriakou" Children's Hospital, Athens, Greece.
Osteoporos Int. 2017 Mar;28(3):945-953. doi: 10.1007/s00198-016-3802-5. Epub 2016 Oct 20.
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.
研究 1 型糖尿病（T1D）患儿和青少年血浆 Dickkopf-1 分布，并将其与代谢性骨标志物和骨密度（BMD）相关联。
我们评估了 40 名 T1D 患儿（平均年龄±标准差 13.04±3.53 岁，T1D 病程 5.15±3.33 年）和 40 名年龄和性别匹配的健康对照者（年龄 12.99±3.3 岁）。测定 Dickkopf-1 和骨代谢标志物，双能 X 线吸收法（DXA）评估全身和腰椎 BMD。
Dickkopf-1 呈正态分布，T1D 患者的水平较高（13.56±5.34 vs 11.35±3.76 pmol/L，p=0.024）。男孩和青春期前儿童的水平较高。Dickkopf-1 与 T1D 患者的骨保护素和空腹血糖呈正相关，而与对照组的 Sclerostin 和总可溶性核因子κB 受体激活剂配体（s-RANKL）呈正相关。两组均与 C 端肽交联（CTX）、骨钙素、碱性磷酸酶、磷酸盐和胰岛素样生长因子 1（IGF1）呈正相关。对照组腰椎 Z 评分与 Dickkopf-1 呈正相关，而患者则呈负相关趋势。
T1D 患儿和青少年的 Dickkopf-1 水平升高可能表明 Wnt/β-catenin 系统下调，成骨细胞激活降低，破骨细胞信号增强。Dickkopf-1 可能是 T1D 骨病的重要贡献者。未来的治疗可能集中在 Wnt/β-catenin 代谢途径上。
