Document Detail


Plasma Dickkopf1 (DKK1) concentrations negatively associate with atherosclerotic calcified plaque in African-Americans with type 2 diabetes.
MedLine Citation:
PMID:  23125289     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Bone mineral density (BMD) and atherosclerotic arterial calcified plaque (CP) demonstrate inverse relationships through unknown mechanisms. Dickkopf-1 (DKK1) is an endogenous inhibitor of bone formation, and serum DKK1 has been associated with impaired osteoblast activation and susceptibility to bone loss. Plasma DKK1, BMD in the spine, and CP in three arterial beds were assessed in African-Americans (AAs) to determine relationships of serum DKK1 with atherosclerotic vascular calcification.
METHODS: Plasma DKK1, computed tomography-derived trabecular volumetric BMD (vBMD) in thoracic and lumbar vertebrae, and coronary artery, carotid artery, and aortoiliac CP were measured in 450 unrelated AAs with type 2 diabetes. Generalized linear models were fitted to test for associations between DKK1, vBMD, and CP.
RESULTS: Participants were 56% female with mean/SD/median age of 55.4/9.5/55.0 yr, diabetes duration of 10.3/8.2/8.0 yr, plasma DKK1 of 481.6/271.8/417 pg/ml, coronary artery CP mass score of 284/648/13, carotid artery CP mass score of 46/132/0, and aortoiliac CP mass score of 1613/2910/282. Adjusting for age, sex, body mass index, mean arterial blood pressure, smoking, hemoglobin A(1c), and low-density lipoprotein-cholesterol, DKK1 was inversely associated with coronary artery and aortoiliac CP [parameter estimates -0.0011 (P = 0.0137) and -0.0010 (P = 0.0214), respectively], with a trend for carotid artery CP (P = 0.1404). No associations were observed between DKK1 and vBMD in the thoracic or lumbar vertebrae.
CONCLUSIONS: Plasma DKK1 levels were inversely associated with coronary artery and aortoiliac CP, but not vBMD, in this cross-sectional study of AAs with type 2 diabetes. DKK1 may play a role in vascular mineral metabolism in this clinical setting.
Authors:
Thomas C Register; Keith A Hruska; Jasmin Divers; Donald W Bowden; Nicholette D Palmer; J Jeffrey Carr; Lynne E Wagenknecht; R Caresse Hightower; Jianzhao Xu; S Carrie Smith; Dennis J Dietzen; Carl D Langefeld; Barry I Freedman
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-11-02
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  98     ISSN:  1945-7197     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-07     Completed Date:  2013-03-07     Revised Date:  2014-04-08    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E60-5     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
African Americans / statistics & numerical data*
Aged
Bone Density / physiology
Calcinosis / blood*,  complications,  epidemiology,  ethnology
Cross-Sectional Studies
Diabetes Mellitus, Type 2 / blood*,  complications,  epidemiology,  ethnology
Female
Humans
Intercellular Signaling Peptides and Proteins / analysis,  blood*,  physiology
Male
Middle Aged
Osmolar Concentration
Plaque, Atherosclerotic / blood*,  complications,  epidemiology,  ethnology
Grant Support
ID/Acronym/Agency:
AR48797/AR/NIAMS NIH HHS; HL67348/HL/NHLBI NIH HHS; M01 RR07122/RR/NCRR NIH HHS; R01 DK070790/DK/NIDDK NIH HHS; R01 DK071891/DK/NIDDK NIH HHS; R01 DK071891/DK/NIDDK NIH HHS; R01 DK089137/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/DKK1 protein, human; 0/Intercellular Signaling Peptides and Proteins
Comments/Corrections

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