Background: Decreased bone mineral density (BMD) and increased fracture risk have consistently been observed in type 1 diabetes mellitus (T1DM). The influence of T1DM on BMD seems to depend on gender or patients age and to occur early after T1DM diagnosis. The mechanisms of decreased BMD in T1DM patients are still unknown.
Objective and hypotheses: To investigate the serum levels of dickkopf-1 (DKK-1), a Wnt signaling inhibitor which decreases bone formation and increases bone resorption, in children and adolescents with T1DM and to evaluate the relationship with glycemic control and bone biomarkers.
Method: This cross-sectional study included 53 T1DM children and adolescents (mean age 12.1±3.3 years) and 50 sex and age-matched controls. Phosphorus, total and ionized calcium, osteocalcin, alkaline phosphatase, PTH and 25 (OH)-vitamin D values were determined. DKK1 was measured in the sera of T1DM patients and controls by ELISA. Bone mineral status was measured by quantitative ultrasonography (QUS).
Results: T1DM patients showed a significant reduction of BTT-z-score compared to controls (P=0.01). Higher DKK-1 levels were found in patients than in controls (3344±961 vs 2450±684 pg/ml, P<0.001). The DKK-1 levels positively correlated with HbA1c values (r=0.353, P=0.01). Furthermore, with adjustment for age HbA1c inversely correlated with BTT-z-score, AdSos-z-score, osteocalcin, alkaline phosphatase, 25 (OH)-vitamin D, as well as directly correlated with daily insulin dosage and T1DM duration. We also found that in T1DM patients DKK-1 serum levels inversely correlated with PTH, osteocalcin, and AdSos-z-score. Additionally, the T1DM duration was indirectly correlated with alkaline phosphatase, 25 (OH)-vitamin D and BTT-z-score. Multiple regression analysis showed that DKK-1 serum levels were best predicted by AdSos-z-score, alkaline phosphatase, 25 (OH)-vitamin D and HbA1c (r=0.61, P<0.0001).
Conclusion: In conclusion, children and adolescents with T1DM presented a reduction of bone mineral status associated to poor glycemic control and increased DKK-1 serum levels.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology