ESPE Abstracts (2015) 84 P-1-25

Lower Bone Mineral Density in Type 1 Diabetes Mellitus (T1DM) is Probably Associated with Wnt/[beta]-Catenin Pathway Downregulation Through Increased Dickkopf-1 Levels

Kyriaki Karavanakia, Charalampos Tsentidisa, Lydia Kossivaa, Antonios Marmarinosb, Artemis Doulgerakic & Dimitrios Gourgiotisb

aSecond Pediatric Department, University of Athens, Diabetic Clinic, ‘P&A Kyriakou’ Children’s Hospital, Athens, Greece; bSecond Pediatric Department, Biochemistry Laboratory, University of Athens, ‘P&A Kyriakou’ Children’s Hospital, Athens, Greece; cDepartment of Bone and Mineral Metabolism, Institute of Child Health, ‘Aghia Sophia’ Children’s Hospital, Athens, Greece

Background: Disruption of many bone metabolic pathways and reduced bone mass are associated with diabetes mellitus. Increased fracture risk and elevated Dickkopf-1 and sclerostin levels, which are inhibitors of Wnt/β-catenin pathway, have been found in adult T2DM patients, but no relevant data exist on childhood T1DM.

Objective and hypotheses: We aimed at studying plasma Dickkopf-1 and sclerostin concentration in children and adolescents with T1DM and controls. We subsequently correlated Dickkopf-1 and sclerostin levels with metabolic bone markers and bone mineral density (BMD).

Method: We evaluated 40 children and adolescents with T1DM (mean±SD age:13.04±3.53 years, T1DM duration:5.15±3.33 years), along with 40 healthy matched controls (age 12.99±3.3 years). Dickkopf-1, sclerostin, receptor activator of Nuclear factor-KappaB Ligand (s-RANKL), osteoprotegerin, osteocalcin, C-telopeptide crosslinks-CTX, electrolytes, PTH, total 25 (OH) D were measured and lumbar spine along with total body BMD were evaluated.

Results: Patients with T1DM had lower values of L1-L4 (−0.17±1.08 vs 0.23±0.96, P=0.035) and total body BMD z-score (0.23±1.01 vs 0.56±0.77, P=0.04) than matched controls and higher Dickkopf-1 levels (13.56±5.34 vs 11.35±3.76 pmol/l, P=0.0194). A trend for lower Dickkopf-1 values was found in girls (13.36±4.04 vs 11.72±5.14 pmol/l, P=0.06) and in pubertal children (13.61±4.87 vs 11.83±4.56 pmol/l, P=0.054). Dickkopf-1 correlated with Sclerostin and L1-L4 BMD z-score only in controls and with Osteoprotegerin and i-Phosphorus only in patients, indicating bone metabolism alterations in T1DM. In both groups a significant correlation with log (CTX) and √ALP was found. A significant association of Dickkopf-1 with IGF1 and insulin dose was also found in patients.

Conclusion: Higher levels of Dickkopf-1 were found in T1DM children and adolescents, indicating a downregulated Wnt signaling system and possible lower osteoblast activation that could be associated with T1DM osteopathy.

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