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Diabetes Research and Clinical PracticeVolume 139, May 2018, Pages 179-187

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

  • Lalić, K.,
  • Nedeljković, M.,
  • Jotić, A.,
  • Babić, R.,
  • Rajković, N.,
  • Popović, L.,
  • Lukić, L.,
  • Miličić, T.,
  • Singh Lukač, S.,
  • Stošić, L.,
  • Maćešić, M.,
  • Rasulić, I.,
  • Gajović, J.S.,
  • Lalić, N.M.
  • View Correspondence (jump link)
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  • aFaculty of Medicine, University of Belgrade, Dr. Subotića 8, Belgrade, 11000, Serbia
  • bClinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia, Dr. Subotića 13, Belgrade, 11000, Serbia
  • cClinic for Cardiology, Clinical Center of Serbia, Koste Todorovića 8, Belgrade, 11000, Serbia

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. © 2018 Elsevier B.V.

Author keywords

Coronary arteries endothelial dysfunctionInsulin secretionInsulin sensitivityPAI-1Small dense LDL

Indexed keywords

EMTREE drug terms:acetylcholineinsulinlipoproteinplasminogen activator inhibitor 1
EMTREE medical terms:adultArticleclinical articlecontrolled studycoronary angiographycoronary arterycoronary artery diseasecoronary artery spasmcorrelation analysisdisease associationdisposition indexendothelial dysfunctionfemalegel electrophoresishomeostasis model assessmenthumaninsulin releaseinsulin resistanceintravenous glucose tolerance testlipoprotein blood levelmalemiddle agedparticle sizeprotein blood levelrating scalecoronary blood vesselendothelium cellinsulin resistancemetabolismpathologyphysiology
MeSH:Coronary VesselsEndothelial CellsFemaleHumansInsulin ResistanceMaleMiddle Aged

Chemicals and CAS Registry Numbers:

acetylcholine, 51-84-3, 60-31-1, 66-23-9; insulin, 9004-10-8; plasminogen activator inhibitor 1, 140208-23-7

Funding details

  • 1

    This study was supported by the grant number 175097 from Ministry of Sciences Republic of Serbia .

  • ISSN: 01688227
  • CODEN: DRCPE
  • Source Type: Journal
  • Original language: English
  • DOI: 10.1016/j.diabres.2018.03.005
  • PubMed ID: 29526680
  • Document Type: Article
  • Publisher: Elsevier Ireland Ltd

  Lalić, K.; Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia, Dr. Subotića 13, Belgrade, Serbia;
© Copyright 2018 Elsevier B.V., All rights reserved.

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