Association of apolipoprotein C3 with insulin resistance and coronary artery calcium in patients with type 1 diabetes

J Clin Lipidol. 2021 Jan-Feb;15(1):235-242. doi: 10.1016/j.jacl.2020.10.006. Epub 2020 Oct 31.

Abstract

Background: Apolipoprotein C3 (APOC3) is a risk factor for incident coronary artery disease in people with type 1 diabetes (T1D). The pathways that link elevated APOC3 levels to an increased risk of incident cardiovascular disease in people with T1D are not understood.

Objective: To explore potential mechanisms, we investigated the association of APOC3 with insulin resistance and coronary artery calcium (CAC).

Methods: In a random subcohort of participants with T1D from Coronary Artery Calcification in Type 1 Diabetes (n = 134), serum APOC3, high-density lipoprotein (HDL)-associated APOC3, and retinol binding protein 4 (RBP4; a potential marker of insulin resistance) were measured by targeted mass spectrometry. We used linear regression to evaluate associations of serum APOC3 and HDL-APOC3 with APOB, non-HDL cholesterol, serum- and HDL-associated RBP4, and estimated insulin sensitivity and logistic regression to evaluate association with presence of CAC, adjusted for age, sex, and diabetes duration.

Results: Serum APOC3 correlated positively with APOB and non-HDL cholesterol and was associated with increased odds of CAC (odds ratio: 1.68, P = .024). Estimated insulin sensitivity was not associated with serum- or HDL-RBP4 but was negatively associated with serum APOC3 in men (ß estimate: -0.318, P = .0040) and decreased odds of CAC (odds ratio: 0.434, P = .0023).

Conclusions: Serum APOC3 associates with increased insulin resistance and CAC in T1D.

Keywords: Apolipoproteins; Diabetes; Epidemiology; HDL; Insulin resistance.

MeSH terms

  • Adult
  • Apolipoprotein C-III* / blood
  • Calcium* / blood
  • Calcium* / metabolism
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / metabolism
  • Coronary Vessels / metabolism
  • Coronary Vessels / pathology
  • Diabetes Mellitus, Type 1* / blood
  • Diabetes Mellitus, Type 1* / complications
  • Diabetes Mellitus, Type 1* / metabolism
  • Female
  • Humans
  • Insulin Resistance*
  • Male
  • Middle Aged
  • Retinol-Binding Proteins, Plasma / analysis
  • Retinol-Binding Proteins, Plasma / metabolism

Substances

  • Apolipoprotein C-III
  • Calcium
  • RBP4 protein, human
  • Retinol-Binding Proteins, Plasma
  • APOC3 protein, human