PMID- 25037197
OWN - NLM
STAT- MEDLINE
DCOM- 20150928
LR  - 20240109
IS  - 2047-9980 (Electronic)
IS  - 2047-9980 (Linking)
VI  - 3
IP  - 4
DP  - 2014 Jul 18
TI  - Circulating dickkopf-1 in diabetes mellitus: association with platelet activation 
      and effects of improved metabolic control and low-dose aspirin.
LID - 10.1161/JAHA.114.001000 [doi]
LID - e001000
AB  - BACKGROUND: Dickkopf-1 (DKK-1) is a major regulator of the Wnt signaling pathway, 
      involved in inflammation, atherogenesis, and the regulation of glucose 
      metabolism. Because platelets are major contributors to circulating levels of 
      DKK-1 in other clinical settings, we aimed at characterizing the platelet 
      contribution to DKK-1 in type 2 diabetes mellitus (T2DM) and evaluating 
      associations of DKK-1 with glucose metabolism, platelet activation, and 
      endothelial dysfunction. METHODS AND RESULTS: A cross-sectional comparison of 
      DKK-1, soluble CD40L (sCD40L; reflecting platelet-mediated inflammation), 
      asymmetric dimethylarginine (ADMA; marker of endothelial dysfunction), and 
      urinary 11-dehydro-thromboxane B2 (in vivo marker of platelet activation) was 
      performed among 214 diabetic patients (90 receiving aspirin at 100 mg/day) and 30 
      healthy controls. Plasma DKK-1 levels were markedly higher in patients with T2DM 
      than in healthy patients (P<0.0001). DKK-1 levels were significantly lower in 
      diabetic patients receiving compared with those not on aspirin treatment 
      (P=0.008); in the latter, DKK-1 was significantly correlated with 
      11-dehydro-thromboxane B2, ADMA, and CD40L (rho=0.303. P<0.0001, rho=0.45. P<0.0001, 
      and rho=0.37, P<0.0001, respectively) but not with glycemic control or DM duration. 
      Among patients not receiving aspirin, improvement of metabolic control in a 
      subgroup of newly diagnosed patients treated with acarbose for 20 weeks and in a 
      group treated with rosiglitazone for 24 weeks was associated with concurrent 
      significant reductions in DKK-1 (P=0.005 and P=0.004) and 11-dehydro-thromboxane 
      B2 (P=0.005 and P=0.004). CONCLUSIONS: Circulating DKK-1 is increased in T2DM and 
      associated with endothelial dysfunction and platelet activation. Plasma DKK-1 
      levels are reduced with improvement of glycemic control and low-dose aspirin 
      treatment.
CI  - (c) 2014 The Authors. Published on behalf of the American Heart Association, Inc., 
      by Wiley Blackwell.
FAU - Lattanzio, Stefano
AU  - Lattanzio S
AD  - Center of Excellence on Aging, "G. d'Annunzio" University of Chieti, Italy (S.L., 
      F.S., R.L., N.V., P.D.F., G.F., A.C., G.D.).
FAU - Santilli, Francesca
AU  - Santilli F
AD  - Center of Excellence on Aging, "G. d'Annunzio" University of Chieti, Italy (S.L., 
      F.S., R.L., N.V., P.D.F., G.F., A.C., G.D.).
FAU - Liani, Rossella
AU  - Liani R
AD  - Center of Excellence on Aging, "G. d'Annunzio" University of Chieti, Italy (S.L., 
      F.S., R.L., N.V., P.D.F., G.F., A.C., G.D.).
FAU - Vazzana, Natale
AU  - Vazzana N
AD  - Center of Excellence on Aging, "G. d'Annunzio" University of Chieti, Italy (S.L., 
      F.S., R.L., N.V., P.D.F., G.F., A.C., G.D.).
FAU - Ueland, Thor
AU  - Ueland T
AD  - Research Institute of Internal Medicine, Oslo University Hospital, 
      Rikshospitalet, Oslo, Norway (T.U., A.).
FAU - Di Fulvio, Patrizia
AU  - Di Fulvio P
AD  - Center of Excellence on Aging, "G. d'Annunzio" University of Chieti, Italy (S.L., 
      F.S., R.L., N.V., P.D.F., G.F., A.C., G.D.).
FAU - Formoso, Gloria
AU  - Formoso G
AD  - Center of Excellence on Aging, "G. d'Annunzio" University of Chieti, Italy (S.L., 
      F.S., R.L., N.V., P.D.F., G.F., A.C., G.D.).
FAU - Consoli, Agostino
AU  - Consoli A
AD  - Center of Excellence on Aging, "G. d'Annunzio" University of Chieti, Italy (S.L., 
      F.S., R.L., N.V., P.D.F., G.F., A.C., G.D.).
FAU - Aukrust, Pal
AU  - Aukrust P
AD  - Research Institute of Internal Medicine, Oslo University Hospital, 
      Rikshospitalet, Oslo, Norway (T.U., A.).
FAU - Davi, Giovanni
AU  - Davi G
AD  - Center of Excellence on Aging, "G. d'Annunzio" University of Chieti, Italy (S.L., 
      F.S., R.L., N.V., P.D.F., G.F., A.C., G.D.).
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140718
PL  - England
TA  - J Am Heart Assoc
JT  - Journal of the American Heart Association
JID - 101580524
RN  - 0 (Biomarkers)
RN  - 0 (DKK1 protein, human)
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Platelet Aggregation Inhibitors)
RN  - 0 (hemoglobin A1c protein, human)
RN  - 147205-72-9 (CD40 Ligand)
RN  - 54397-85-2 (Thromboxane B2)
RN  - 63CV1GEK3Y (N,N-dimethylarginine)
RN  - 67910-12-7 (11-dehydro-thromboxane B2)
RN  - 94ZLA3W45F (Arginine)
RN  - R16CO5Y76E (Aspirin)
SB  - IM
MH  - Aged
MH  - Arginine/analogs & derivatives/blood
MH  - Aspirin/*therapeutic use
MH  - Biomarkers/blood
MH  - CD40 Ligand/*blood
MH  - Cardiovascular Diseases/*prevention & control
MH  - Case-Control Studies
MH  - Cross-Sectional Studies
MH  - Diabetes Mellitus, Type 2/*blood/drug therapy
MH  - Female
MH  - Glycated Hemoglobin/metabolism
MH  - Humans
MH  - Hypoglycemic Agents/therapeutic use
MH  - Intercellular Signaling Peptides and Proteins/*blood
MH  - Male
MH  - Middle Aged
MH  - *Platelet Activation
MH  - Platelet Aggregation Inhibitors/*therapeutic use
MH  - Thromboxane B2/analogs & derivatives/urine
MH  - Wnt Signaling Pathway
PMC - PMC4310390
OTO - NOTNLM
OT  - DKK-1
OT  - diabetes mellitus
OT  - endothelial dysfunction
OT  - inflammation
OT  - platelet activation
OT  - platelet-derived factor
EDAT- 2014/07/20 06:00
MHDA- 2015/09/29 06:00
PMCR- 2014/08/01
CRDT- 2014/07/20 06:00
PHST- 2014/07/20 06:00 [entrez]
PHST- 2014/07/20 06:00 [pubmed]
PHST- 2015/09/29 06:00 [medline]
PHST- 2014/08/01 00:00 [pmc-release]
AID - jah3586 [pii]
AID - 10.1161/JAHA.114.001000 [doi]
PST - epublish
SO  - J Am Heart Assoc. 2014 Jul 18;3(4):e001000. doi: 10.1161/JAHA.114.001000.