Endothelial dysfunction of coronary arteries in subjects without diabetes: An association with both insulin resistance and impaired insulin secretion response

Diabetes Res Clin Pract. 2018 May:139:179-187. doi: 10.1016/j.diabres.2018.03.005. Epub 2018 Mar 9.

Abstract

Aims: This study was aimed to compare insulin sensitivity and secretion response, lipoprotein and plasminogen activator inhibitor 1 (PAI-1) levels between the subjects with and without coronary artery endothelial dysfunction (ED).

Methods: ED was detected by intracoronary injection of acetylcholine (ACh) in 47 nondiabetes subjects without stenotic coronary arteries, selected from 316 consecutive patients with coronary angiography performed for suspected coronary artery disease. The subjects were divided into two groups: presence of ACh-induced coronary spasm (group ED+, N = 30) and absence of ACh-induced coronary spasm (group ED-, N = 17). Insulin sensitivity (Si) was evaluated by frequently sampled intravenous glucose tolerance test (FSIGTT) with minimal model analysis and by HOMA-IR, insulin secretion by acute insulin response (AIR) (calculated from the first 8 min of FSIGTT) and by disposition index (DI) (Si × AIR). Lipids and PAI-1 levels were determined enzymatically, and LDL particle size by gradient gel electrophoresis.

Results: Si was significantly lower (4.22 ± 0.62 vs 6.98 ± 1.47 min-1/mU/l × 104; p < 0.05) while HOMA-IR was significantly higher in ED + group vs ED- group (2.8 ± 0.3 vs 1.7 ± 0.2; p < 0.05). Simultaneously, AIR and DI was significantly lower in ED + vs ED- groups (p < 0.05 and p < 0.01, respectively). Investigated groups did not differ in fasting lipid levels but ED+ group had significantly smaller LDL particles (p < 0.01) and higher PAI-1 levels (p < 0.05). Regression analysis shown that DI was a strong independent predictor of appearance of ED, together with PAI-1 and LDL particle size.

Conclusions: Both insulin resistance and impairment in insulin secretion response strongly correlate with coronary ED in subjects without diabetes.

Keywords: Coronary arteries endothelial dysfunction; Insulin secretion; Insulin sensitivity; PAI-1; Small dense LDL.

MeSH terms

  • Coronary Vessels / pathology*
  • Endothelial Cells / metabolism*
  • Female
  • Humans
  • Insulin Resistance / physiology*
  • Male
  • Middle Aged