PMID- 26069232
OWN - NLM
STAT- MEDLINE
DCOM- 20151014
LR  - 20181113
IS  - 1524-4636 (Electronic)
IS  - 1079-5642 (Print)
IS  - 1079-5642 (Linking)
VI  - 35
IP  - 8
DP  - 2015 Aug
TI  - Plasma apolipoprotein C-III levels, triglycerides, and coronary artery 
      calcification in type 2 diabetics.
PG  - 1880-8
LID - 10.1161/ATVBAHA.115.305415 [doi]
AB  - OBJECTIVE: Triglyceride-rich lipoproteins have emerged as causal risk factors for 
      developing coronary heart disease independent of low-density lipoprotein 
      cholesterol levels. Apolipoprotein C-III (ApoC-III) modulates triglyceride-rich 
      lipoprotein metabolism through inhibition of lipoprotein lipase and hepatic 
      uptake of triglyceride-rich lipoproteins. Mutations causing loss-of-function of 
      ApoC-III lower triglycerides and reduce coronary heart disease risk, suggestive 
      of a causal role for ApoC-III. Little data exist about the relationship of 
      ApoC-III, triglycerides, and atherosclerosis in patients with type 2 diabetes 
      mellitus (T2DM). Here, we examined the relationships between plasma ApoC-III, 
      triglycerides, and coronary artery calcification in patients with T2DM. APPROACH 
      AND RESULTS: Plasma ApoC-III levels were measured in a cross-sectional study of 
      1422 subjects with T2DM but without clinically manifest coronary heart disease. 
      ApoC-III levels were positively associated with total cholesterol (Spearman 
      r=0.36), triglycerides (r=0.59), low-density lipoprotein cholesterol (r=0.16), 
      fasting glucose (r=0.16), and glycosylated hemoglobin (r=0.12; P<0.0001 for all). 
      In age, sex, and race-adjusted analysis, ApoC-III levels were positively 
      associated with coronary artery calcification (Tobit regression ratio, 1.78; 95% 
      confidence interval, 1.27-2.50 per SD increase in ApoC-III; P<0.001). As expected 
      for an intermediate mediator, these findings were attenuated when adjusted for 
      both triglycerides (Tobit regression ratio, 1.43; 95% confidence interval, 
      0.94-2.18; P=0.086) and separately for very low-density lipoprotein cholesterol 
      (Tobit regression ratio, 1.14; 95% confidence interval, 0.75-1.71; P=0.53). 
      CONCLUSIONS: In persons with T2DM, increased plasma ApoC-III is associated with 
      higher triglycerides, less favorable cardiometabolic phenotypes, and higher 
      coronary artery calcification, a measure of subclinical atherosclerosis. 
      Therapeutic inhibition of ApoC-III may thus be a novel strategy for reducing 
      plasma triglyceride-rich lipoproteins and cardiovascular risk in T2DM.
CI  - (c) 2015 American Heart Association, Inc.
FAU - Qamar, Arman
AU  - Qamar A
AD  - From the Department of Medicine, Cardiovascular Institute, Perelman School of 
      Medicine, University of Pennsylvania, Philadelphia (A.Q., S.A.K., D.J.R., 
      M.P.R.); Cardiology Division, Department of Medicine, Massachusetts General 
      Hospital, Boston (A.V.K.); and Division of Cardiology, Department of Medicine, 
      University of California at San Francisco (A.Q.).
FAU - Khetarpal, Sumeet A
AU  - Khetarpal SA
AD  - From the Department of Medicine, Cardiovascular Institute, Perelman School of 
      Medicine, University of Pennsylvania, Philadelphia (A.Q., S.A.K., D.J.R., 
      M.P.R.); Cardiology Division, Department of Medicine, Massachusetts General 
      Hospital, Boston (A.V.K.); and Division of Cardiology, Department of Medicine, 
      University of California at San Francisco (A.Q.).
FAU - Khera, Amit V
AU  - Khera AV
AD  - From the Department of Medicine, Cardiovascular Institute, Perelman School of 
      Medicine, University of Pennsylvania, Philadelphia (A.Q., S.A.K., D.J.R., 
      M.P.R.); Cardiology Division, Department of Medicine, Massachusetts General 
      Hospital, Boston (A.V.K.); and Division of Cardiology, Department of Medicine, 
      University of California at San Francisco (A.Q.).
FAU - Qasim, Atif
AU  - Qasim A
AD  - From the Department of Medicine, Cardiovascular Institute, Perelman School of 
      Medicine, University of Pennsylvania, Philadelphia (A.Q., S.A.K., D.J.R., 
      M.P.R.); Cardiology Division, Department of Medicine, Massachusetts General 
      Hospital, Boston (A.V.K.); and Division of Cardiology, Department of Medicine, 
      University of California at San Francisco (A.Q.).
FAU - Rader, Daniel J
AU  - Rader DJ
AD  - From the Department of Medicine, Cardiovascular Institute, Perelman School of 
      Medicine, University of Pennsylvania, Philadelphia (A.Q., S.A.K., D.J.R., 
      M.P.R.); Cardiology Division, Department of Medicine, Massachusetts General 
      Hospital, Boston (A.V.K.); and Division of Cardiology, Department of Medicine, 
      University of California at San Francisco (A.Q.). muredach@mail.med.upenn.edu 
      rader@mail.med.upenn.edu.
FAU - Reilly, Muredach P
AU  - Reilly MP
AD  - From the Department of Medicine, Cardiovascular Institute, Perelman School of 
      Medicine, University of Pennsylvania, Philadelphia (A.Q., S.A.K., D.J.R., 
      M.P.R.); Cardiology Division, Department of Medicine, Massachusetts General 
      Hospital, Boston (A.V.K.); and Division of Cardiology, Department of Medicine, 
      University of California at San Francisco (A.Q.). muredach@mail.med.upenn.edu 
      rader@mail.med.upenn.edu.
LA  - eng
GR  - F30 HL124967/HL/NHLBI NIH HHS/United States
GR  - R37 HL055323/HL/NHLBI NIH HHS/United States
GR  - R01 HL113147/HL/NHLBI NIH HHS/United States
GR  - R01 DK090505/DK/NIDDK NIH HHS/United States
GR  - U01 HL108636/HL/NHLBI NIH HHS/United States
GR  - R01 HL111694/HL/NHLBI NIH HHS/United States
GR  - K24 HL107643/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150611
PL  - United States
TA  - Arterioscler Thromb Vasc Biol
JT  - Arteriosclerosis, thrombosis, and vascular biology
JID - 9505803
RN  - 0 (Apolipoprotein C-III)
RN  - 0 (Biomarkers)
RN  - 0 (Blood Glucose)
RN  - 0 (Triglycerides)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Apolipoprotein C-III/*blood
MH  - Biomarkers/blood
MH  - Blood Glucose/analysis
MH  - Coronary Artery Disease/blood/diagnosis/*etiology
MH  - Cross-Sectional Studies
MH  - Diabetes Mellitus, Type 2/blood/*complications/diagnosis
MH  - Diabetic Angiopathies/blood/diagnosis/*etiology
MH  - Dyslipidemias/blood/*complications/diagnosis
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Phenotype
MH  - Philadelphia
MH  - Risk Factors
MH  - Triglycerides/*blood
MH  - Up-Regulation
MH  - Vascular Calcification/blood/diagnosis/*etiology
PMC - PMC4556282
MID - NIHMS697393
OTO - NOTNLM
OT  - apolipoproteins
OT  - atherosclerosis
OT  - risk factors
OT  - type 2 diabetes mellitus
EDAT- 2015/06/13 06:00
MHDA- 2015/10/16 06:00
PMCR- 2016/08/01
CRDT- 2015/06/13 06:00
PHST- 2014/12/27 00:00 [received]
PHST- 2015/06/02 00:00 [accepted]
PHST- 2015/06/13 06:00 [entrez]
PHST- 2015/06/13 06:00 [pubmed]
PHST- 2015/10/16 06:00 [medline]
PHST- 2016/08/01 00:00 [pmc-release]
AID - ATVBAHA.115.305415 [pii]
AID - 10.1161/ATVBAHA.115.305415 [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 2015 Aug;35(8):1880-8. doi: 
      10.1161/ATVBAHA.115.305415. Epub 2015 Jun 11.