Contribution of ApoCIII to Diabetic Dyslipidemia and Treatment With Volanesorsen

Rev Cardiovasc Med. 2018 Mar 30;19(1):13-19. doi: 10.31083/j.rcm.2018.01.890.

Abstract

Diabetic dyslipidemia in type 2 diabetes (T2DM) is characterized by elevated levels of triglycerides (TG), decreased levels of high density lipoprotein-cholesterol (HDL-C), elevated levels of low density lipoprotein-cholesterol (LDLC), and the predominance of small and dense LDL particles (sdLDL). The mechanism underlying diabetic dyslipidemia remains unclear. Insulin resistance is believed to be an important determinant. Mechanisms underlying insulin resistance-induced diabetic dyslipidemia seem to be related to apolipoprotein CIII (ApoCIII), a known inhibitor of lipoprotein lipase. The concentration of very low density lipoprotein1 (VLDL1) with a higher TG content and abundant ApoCIII was found to be significantly elevated in patients with T2DM. Recently, volanesorsen as a promising ApoIII inhibitor was shown to improve the lipid profile in patients with diabetic dyslipidemia. Herein, this paper will review recent advance in pathophysiology of diabetic dyslipidemia and the role of ApoCIII in this condition, with focus on describing a novel drug volanesorsen as potential treatment strategy.

Keywords: Apolipoprotein CIII; diabetic dyslipidemia; high density lipoprotein-cholesterol; low density lipoprotein-cholesterol; type 2 diabetes mellitus; very low density lipoprotein; volanesorsen.

Publication types

  • Review

MeSH terms

  • Apolipoprotein C-III / blood*
  • Biomarkers / blood
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / diagnosis
  • Dyslipidemias / blood
  • Dyslipidemias / diagnosis
  • Dyslipidemias / drug therapy*
  • Dyslipidemias / etiology
  • Humans
  • Hypolipidemic Agents / adverse effects
  • Hypolipidemic Agents / therapeutic use*
  • Insulin Resistance
  • Oligonucleotides / adverse effects
  • Oligonucleotides / therapeutic use*
  • Treatment Outcome

Substances

  • Apolipoprotein C-III
  • Biomarkers
  • Hypolipidemic Agents
  • ISIS 304801
  • Oligonucleotides