title: Insulin resistance and acute glucose changes determine arterial elastic properties and coronary flow reserve in dysglycaemic and first-degree relatives of diabetic patients.
abstract: BACKGROUND
  Insulin resistance is linked to endothelial dysfunction. We investigated whether first-degree relatives of type-2 diabetes patients (FDR) present differences in vascular function at baseline and during postprandial hyperglycemia compared to dysglycaemic or normoglycaemic subjects.
  
  
  METHODS
  We studied 40 FDR with normal oral glucose test (OGTT), 40 subjects with abnormal OGTT (dysglycaemic) and 20 subjects with normal OGTT without parental history of diabetes (normoglycaemic) with similar clinical characteristics. Glucose, insulin, pulse wave velocity (PWV), central systolic blood pressure (cSBP) and augmentation index (AI) were measured at 0, 30, 60, 90 and 120min during OGTT. Coronary flow reserve (CFR) was assessed using Doppler echocardiography at 0 and 120min after OGTT. Insulin sensitivity was evaluated using Matsuda and insulin sensitivity index (ISI).
  
  
  RESULTS
  FDR and dysglycaemics had higher fasting insulin, reduced ISI, Matsuda index as well as reduced CFR (2.54 ± 0.5 vs. 2.45 ± 0.3 vs. 2.74 ± 0.5), increased PWV, (8.9 ± 1.1 vs. 10.3 ± 2.4vs. 8.0 ± 1.5 m/sec), AI (23.8 ± 13.6 vs. 26.5 ± 14.4vs.17.7  ±  14%) and cSBP than normoglycaemics (p < 0.05 for all comparisons). During OGTT, AI was similarly reduced in both normoglycaemic and FDR (p < 0.05) at peak insulin levels (60 min) though FDR had 2-fold higher insulin than normoglycaemics. AI was increased in dysglycaemics after peak glucose levels, at 120 min (p < 0.05). CFR was reduced by 10% and 15% at 120min in FDR and dysglycaemic respectively, while remained unchanged in normoglycaemics (p < 0.05). The percent reduction of CFR was related with the percent increase of glucose levels, ISI and Matsuda index(p < 0.05).
  
  
  CONCLUSIONS
  First-degree relatives and dysglycaemic patients have impaired arterial and coronary microcirculatory function. Insulin resistance determines acute vascular responses during postprandial hyperglycemia. CLINICALTRIALS.
  NCT02244736.
authors.affiliation: 2nd Cardiology Department, Attikon Hospital, University of Athens, Greece. Electronic address: ignoik@otenet.gr.
authors.forename: Ignatios
authors.initials: I
authors.lastname: Ikonomidis
authors.affiliation: 2nd Department of Internal Medicine, Research Unit and Diabetes Centre, Attikon Hospital, University of Athens, Greece.
authors.forename: Vaia
authors.initials: V
authors.lastname: Lambadiari
authors.affiliation: 2nd Cardiology Department, Attikon Hospital, University of Athens, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Pavlidis
authors.affiliation: 2nd Cardiology Department, Attikon Hospital, University of Athens, Greece.
authors.forename: Charalambos
authors.initials: C
authors.lastname: Koukoulis
authors.affiliation: 2nd Department of Internal Medicine, Research Unit and Diabetes Centre, Attikon Hospital, University of Athens, Greece.
authors.forename: Fotini
authors.initials: F
authors.lastname: Kousathana
authors.affiliation: 2nd Department of Internal Medicine, Research Unit and Diabetes Centre, Attikon Hospital, University of Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Varoudi
authors.affiliation: 2nd Department of Internal Medicine, Research Unit and Diabetes Centre, Attikon Hospital, University of Athens, Greece.
authors.forename: Filio
authors.initials: F
authors.lastname: Spanoudi
authors.affiliation: Hellenic National Centre for the Prevention of Diabetes and its Complications HNDC, Greece.
authors.forename: Eirini
authors.initials: E
authors.lastname: Maratou
authors.affiliation: 2nd Cardiology Department, Attikon Hospital, University of Athens, Greece.
authors.forename: John
authors.initials: J
authors.lastname: Parissis
authors.affiliation: 2nd Cardiology Department, Attikon Hospital, University of Athens, Greece.
authors.forename: Helen
authors.initials: H
authors.lastname: Triantafyllidi
authors.affiliation: 2nd Cardiology Department, Attikon Hospital, University of Athens, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Paraskevaidis
authors.affiliation: 2nd Department of Internal Medicine, Research Unit and Diabetes Centre, Attikon Hospital, University of Athens, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Dimitriadis
authors.affiliation: 2nd Cardiology Department, Attikon Hospital, University of Athens, Greece.
authors.forename: John
authors.initials: J
authors.lastname: Lekakis
mesh_terms: D000328:Adult; D001158:Arteries / Q000473:pathology*; D001783:Blood Flow Velocity; D001786:Blood Glucose / Q000032:analysis*; D001794:Blood Pressure; D016022:Case-Control Studies; D003326:Coronary Circulation; D003430:Cross-Sectional Studies; D003920:Diabetes Mellitus / Q000097:blood*; D004452:Echocardiography; D004548:Elasticity; D005192:Family Health; D005260:Female; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D063177:Pulse Wave Analysis
chemical_list: D001786:Blood Glucose
keywords: Arterial stiffness; Coronary circulation; Diabetes; First degree relatives; Insulin resistance; Pulse wave analysis