Plasma apolipoprotein C-III levels, triglycerides, and coronary artery calcification in type 2 diabetics

Arterioscler Thromb Vasc Biol. 2015 Aug;35(8):1880-8. doi: 10.1161/ATVBAHA.115.305415. Epub 2015 Jun 11.


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.

Keywords: apolipoproteins; atherosclerosis; risk factors; type 2 diabetes mellitus.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Apolipoprotein C-III / blood*
  • Biomarkers / blood
  • Blood Glucose / analysis
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / diagnosis
  • Coronary Artery Disease / etiology*
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetic Angiopathies / blood
  • Diabetic Angiopathies / diagnosis
  • Diabetic Angiopathies / etiology*
  • Dyslipidemias / blood
  • Dyslipidemias / complications*
  • Dyslipidemias / diagnosis
  • Female
  • Humans
  • Male
  • Middle Aged
  • Phenotype
  • Philadelphia
  • Risk Factors
  • Triglycerides / blood*
  • Up-Regulation
  • Vascular Calcification / blood
  • Vascular Calcification / diagnosis
  • Vascular Calcification / etiology*


  • Apolipoprotein C-III
  • Biomarkers
  • Blood Glucose
  • Triglycerides