title: Plasma apolipoprotein C-III levels, triglycerides, and coronary artery calcification in type 2 diabetics.
abstract: 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.
  
  
  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.
authors.affiliation: 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.).
authors.forename: Arman
authors.initials: A
authors.lastname: Qamar
authors.affiliation: 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.).
authors.forename: Sumeet A
authors.initials: SA
authors.lastname: Khetarpal
authors.affiliation: 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.).
authors.forename: Amit V
authors.initials: AV
authors.lastname: Khera
authors.affiliation: 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.).
authors.forename: Atif
authors.initials: A
authors.lastname: Qasim
authors.affiliation: 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.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Rader
authors.affiliation: 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.
authors.forename: Muredach P
authors.initials: MP
authors.lastname: Reilly
mesh_terms: D000328:Adult; D000368:Aged; D053305:Apolipoprotein C-III / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D003324:Coronary Artery Disease / Q000097:blood / Q000175:diagnosis / Q000209:etiology*; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000175:diagnosis; D003925:Diabetic Angiopathies / Q000097:blood / Q000175:diagnosis / Q000209:etiology*; D050171:Dyslipidemias / Q000097:blood / Q000150:complications* / Q000175:diagnosis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D015143:Philadelphia; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood*; D015854:Up-Regulation; D061205:Vascular Calcification / Q000097:blood / Q000175:diagnosis / Q000209:etiology*
chemical_list: D053305:Apolipoprotein C-III; D015415:Biomarkers; D001786:Blood Glucose; D014280:Triglycerides
keywords: apolipoproteins; atherosclerosis; risk factors; type 2 diabetes mellitus