Serum dickkopf1 (DKK1), bone metabolism and atherosclerotic disease in patients with type 2 diabetes

Background and objectives: Type 2 diabetes (T2DM) is a risk factor for osteoporotic fractures and cardiovascular disease. The aims of our study were to evaluate serum Dickkopf-1(DKK1) levels in a cohort of T2DM patients and to analyze its relationships with bone metabolism and atheroesclerotic disease (AD). Patients and methods: We studied 126 subjects: T2DM patients (n: 72, mean age 58,2+/-6 years) and non-diabetic subjects (n: 54, mean age 55,4+/-7 years). DKK-1 was measured by enzyme-linked immunosorbent assay (ELISA, Biomedica Gruppe). Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA). The presence of AD (cerebrovascular disease, peripheral arterial disease, ischemic heart disease) was recorded. Intima-media thickness (IMT) was determined by doppler ultra-sonography and aortic calcification by evaluation of lateral view conventional X-rays. Results: We did not find significant differences in DKK1 between groups. Serum DKK1 concentrations were significantly higher in females in total sample (24,3+/-15,2 vs 19,6+/-10,2 pmol/L, p=0,046) and in T2DM group (27,5+/-17,2 vs 19,8+/-8,9 pmol/L, p= 0,025). There was a positive correlation between serum DKK1 and LS BMD in total sample (r= 0,183, p= 0,048). However, we did not find a significant relationship with osteoporosis diagnosis or morphometric vertebral fractures. Serum DKK1 was significantly higher in T2DM patients with AD (26,4+/-14,5 pmol/L vs 19,1+/-11,6 pmol/L, p= 0,026) and also in patients with abnormal IMT (26,4+/-15,1 pmol/L vs 19,8+/-11,3 pmol/L, p= 0,038). In the ROC curve analysis to evaluate the usefulness of DKK-1 as a marker for high risk of AD, the area under the curve was 0,667 (95% confidence interval: 0,538-0,795; p= 0,016). A concentration of 17,3 pmol/L or higher showed a sensitivity of 71,4% and a specificity of 60% to identify an increased risk of AD. Conclusions: Circulating DKK1 levels are higher in T2DM with AD and are associated with an abnormal IMT in this cross-sectional study. DKK1 may be involved in vascular disease of T2DM patients.