title: Relationship of Dickkopf1 (DKK1) with cardiovascular disease and bone metabolism in Caucasian type 2 diabetes mellitus.
abstract: OBJECTIVE
  Dickkopf-1 (DKK1) is a potent inhibitor of Wnt signalling, which exerts anabolic effects on bone and also takes part in the regulation of vascular cells. Our aims were to evaluate serum DKK1 in type 2 diabetes (T2DM) patients and to analyze its relationships with cardiovascular disease (CVD). We also evaluated the relationship between DKK1 and bone metabolism.
  
  
  METHODS
  We conducted a cross-sectional study in which we measured serum DKK1 (ELISA, Biomedica) in 126 subjects: 72 patients with T2DM and 54 non-diabetic subjects. We analysed its relationship with clinical CVD, preclinical CVD expressed as carotid intima media thickness (IMT), and bone metabolism.
  
  
  RESULTS
  T2DM patients with CVD (P = 0,026) and abnormal carotid IMT (P = 0,038) had higher DKK1 concentrations. DKK1 was related to the presence of CVD in T2DM, independently of the presence of risk factors for atherosclerosis. Therefore, for each increase of 28 pg/ml of serum DKK1 there was a 6,2% increase in the risk of CVD in T2DM patients. The ROC curve analysis to evaluate the usefulness of DKK1 as a marker for high risk of CVD showed an area under the curve of 0,667 (95% CI: 0,538-0,795; P = 0,016). In addition, there was a positive correlation between serum DKK1 and spine bone mineral density in the total sample (r =  0,183; P = 0,048).
  
  
  CONCLUSIONS
  In summary, circulating DKK1 levels are higher in T2DM with CVD and are associated with an abnormal carotid IMT in this cross-sectional study. DKK1 may be involved in vascular disease of T2DM patients.
authors.affiliation: Bone Metabolic Unit (RETICEF), Endocrinology Division, Hospital Universitario San Cecilio, Instituto de Investigación Biosanitaria de Granada, Granada, Spain; Endocrinology, Hospital Comarcal del Noroeste, Caravaca de la Cruz, Murcia, Spain.
authors.forename: Antonia
authors.initials: A
authors.lastname: Garcia-Martín
authors.affiliation: Bone Metabolic Unit (RETICEF), Endocrinology Division, Hospital Universitario San Cecilio, Instituto de Investigación Biosanitaria de Granada, Granada, Spain; Endocrinology Unit, Hospital General Universitario Rafael Mendez, Lorca, Murcia, Spain.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Reyes-Garcia
authors.affiliation: Bone Metabolic Unit (RETICEF), Endocrinology Division, Hospital Universitario San Cecilio, Instituto de Investigación Biosanitaria de Granada, Granada, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: García-Fontana
authors.affiliation: Bone Metabolic Unit (RETICEF), Endocrinology Division, Hospital Universitario San Cecilio, Instituto de Investigación Biosanitaria de Granada, Granada, Spain; Proteomic Research Service, Fundación para la Investigación Biosanitaria de Andalucía Oriental -Alejandro Otero- (FIBAO), Granada, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Morales-Santana
authors.affiliation: Department of Morphology and Cellular Biology (RETICEF), Faculty of Medicine, University of Oviedo, Oviedo, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Coto-Montes
authors.affiliation: Critical Care and Emergencies Unit, Hospital Universitario San Cecilio, Granada, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Muñoz-Garach
authors.affiliation: Endocrinology Division, Hospital General de Ciudad Real, Ciudad Real, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Rozas-Moreno
authors.affiliation: Bone Metabolic Unit (RETICEF), Endocrinology Division, Hospital Universitario San Cecilio, Instituto de Investigación Biosanitaria de Granada, Granada, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Muñoz-Torres
mesh_terms: D015519:Bone Density; D002318:Cardiovascular Diseases / Q000097:blood* / Q000150:complications* / Q000378:metabolism; D059168:Carotid Intima-Media Thickness; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications* / Q000378:metabolism; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood* / Q000378:metabolism; D008297:Male; D008875:Middle Aged
chemical_list: C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins