Background: Type 1 diabetes (T1DM) is associated with low bone mineral density (BMD) and bone alterations, probably due to lack of insulin and chronic hyperglycemia. Sclerostin and Dickkopfs-1 (DKK-1) are Wnt signaling inhibitors involved in bone remodelling.
Objective and hypotheses: To assess serum levels of DKK-1 and sclerostin in T1DM children and adolescents on continuous subcutaneous insulin infusion (CSII) or multiple daily therapy (MDI). We hypothesized the involvement of these Wnt signaling inhibitors in the altered bone remodeling associated to diabetes.
Method: One hundred T1DM patients (44 males, 11.58±4.58 yr), T1DM duration 4.21±3.06 yr, and 70 sex and age-matched controls were enrolled. Sixty five patients received CSII and thirty-five MDI. Serum DKK1 and sclerostin were measured by ELISA. BMD was measured by Quantitative ultrasonography (QUS).
Results: The average of BMD Z-scores was within the normal range in patients, but reduced respect to controls. Significant increased serum levels of DKK-1 (3593±1172 vs 2660±664 pg/ml, P<0.006) and sclerostin (29.45±12.32 vs 22.53±8.29 P<0.001) were found in diabetics respect to controls. In particular, DKK-1 and sclerostin levels were higher in patients on MDI than ones on CSII (3744±1266 vs 2962±986, P<0.001; 30.25±13.10 vs 23.63±8.75, P=0.02). Glycaemic control was improved in CSII patients compared to MDI ones (glucose 195 vs 141 mg/dL, P<0.001; HbA1c% 8.35±0.98 vs 7.66±0.66, P<0.001). This improvement was also associated to a significant higher BMI-SDS (0.47±1.03 vs −0.28±0.92, P<0.002) and BMD (BTT-Z-score: 0.44±0.85 vs −0.34±1.21, P<0.02) in CSII compared to MDI patients.
Conclusion: Our study highlighted: 1. the high levels of DKK-1 and sclerostin in T1DM children, and their relationship with altered bone remodelling and glycaemic control; 2. the effect of CSII on the improvement of glycaemic control and bone health in T1DM children.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology