Effects of 6-month eicosapentaenoic acid treatment on postprandial hyperglycemia, hyperlipidemia, insulin secretion ability, and concomitant endothelial dysfunction among newly-diagnosed impaired glucose metabolism patients with coronary artery disease. An open label, single blinded, prospective randomized controlled trial

Cardiovasc Diabetol. 2016 Aug 26;15(1):121. doi: 10.1186/s12933-016-0437-y.


Background: Recent experimental studies have revealed that n-3 fatty acids, such as eicosapentaenoic acid (EPA) regulate postprandial insulin secretion, and correct postprandial glucose and lipid abnormalities. However, the effects of 6-month EPA treatment on postprandial hyperglycemia and hyperlipidemia, insulin secretion, and concomitant endothelial dysfunction remain unknown in patients with impaired glucose metabolism (IGM) and coronary artery disease (CAD).

Methods and results: We randomized 107 newly diagnosed IGM patients with CAD to receive either 1800 mg/day of EPA (EPA group, n = 53) or no EPA (n = 54). Cookie meal testing (carbohydrates: 75 g, fat: 28.5 g) and endothelial function testing using fasting-state flow-mediated dilatation (FMD) were performed before and after 6 months of treatment. The primary outcome of this study was changes in postprandial glycemic and triglyceridemic control and secondary outcomes were improvement of insulin secretion and endothelial dysfunction. After 6 months, the EPA group exhibited significant improvements in EPA/arachidonic acid, fasting triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C). The EPA group also exhibited significant decreases in the incremental TG peak, area under the curve (AUC) for postprandial TG, incremental glucose peak, AUC for postprandial glucose, and improvements in glycometabolism categorization. No significant changes were observed for hemoglobin A1c and fasting plasma glucose levels. The EPA group exhibited a significant increase in AUC-immune reactive insulin/AUC-plasma glucose ratio (which indicates postprandial insulin secretory ability) and significant improvements in FMD. Multiple regression analysis revealed that decreases in the TG/HDL-C ratio and incremental TG peak were independent predictors of FMD improvement in the EPA group.

Conclusions: EPA corrected postprandial hypertriglyceridemia, hyperglycemia and insulin secretion ability. This amelioration of several metabolic abnormalities was accompanied by recovery of concomitant endothelial dysfunction in newly diagnosed IGM patients with CAD. Clinical Trial Registration UMIN Registry number: UMIN000011265 ( https://www.upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000013200&language=E ).

Keywords: Eicosapentaenoic acid; Endothelial dysfunction; Impaired glucose metabolism; Postprandial hyperglycemia; Postprandial hypertriglyceridemia; Postprandial insulin secretion.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / diagnosis
  • Coronary Artery Disease / drug therapy*
  • Coronary Artery Disease / physiopathology
  • Drug Administration Schedule
  • Eicosapentaenoic Acid / administration & dosage*
  • Eicosapentaenoic Acid / adverse effects
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / physiopathology
  • Female
  • Humans
  • Hyperglycemia / blood
  • Hyperglycemia / diagnosis
  • Hyperglycemia / drug therapy*
  • Hyperglycemia / physiopathology
  • Hypertriglyceridemia / blood
  • Hypertriglyceridemia / diagnosis
  • Hypertriglyceridemia / drug therapy*
  • Hypertriglyceridemia / physiopathology
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / adverse effects
  • Hypolipidemic Agents / administration & dosage*
  • Hypolipidemic Agents / adverse effects
  • Inflammation Mediators / blood
  • Insulin / blood
  • Insulin / metabolism*
  • Insulin Secretion
  • Japan
  • Male
  • Middle Aged
  • Postprandial Period*
  • Prospective Studies
  • Recovery of Function
  • Single-Blind Method
  • Time Factors
  • Treatment Outcome
  • Triglycerides / blood
  • Vasodilation / drug effects


  • Biomarkers
  • Blood Glucose
  • Hypoglycemic Agents
  • Hypolipidemic Agents
  • Inflammation Mediators
  • Insulin
  • Triglycerides
  • Eicosapentaenoic Acid