title: Early detection of left ventricular dysfunction in first-degree relatives of diabetic patients by myocardial deformation imaging: The role of endothelial glycocalyx damage.
abstract: BACKGROUND
  First-degree relatives of type-2 diabetes patients (FDR) present insulin resistance. We investigated whether FDR and dysglycaemic subjects demonstrate abnormal endothelial glycocalyx and LV deformation during postprandial hyperglycemia.
  
  
  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). At 0 and 120min of OGTT we measured: a) LV longitudinal strain (LS) of subendocardial, mid-myocardial and subepicardial layers, global LS (GLS), peak twisting (pTw), untwisting velocity (pUtwVel), by speckle tracking echocardiography b) perfused boundary region (PBR) of the sublingual arterial microvessels; high PBR values represent reduced glycocalyx thickness. Insulin resistance was evaluated using insulin sensitivity index (ISI).
  
  
  RESULTS
  ISI was related with baseline PBR, GLS and pTw in all subjects (p<0.05). Compared to normoglycaemics, FDR and dysglycaemics had higher PBR, lower ISI, GLS (-18.4±2.6 and -16.8±2.0 vs. -19.2±2.4%), subendocardial LS (-19.0±4.2 and -17.9±3.0 vs. -20.1±3.4%), pTw (14.4±4.4 and 15.6±6.4 vs. 16.9±6.5deg) and pUtwVel (p<0.05 for all comparisons). A GLS<-18% identified FDR with LV dysfunction (p=0.016). Post-OGTT, GLS and the subendocardial LS decreased while pTw and pUtwVel increased in FDR and dysglycaemics (p<0.05) indicating prevalence of the motion of the subepicardial over a dysfunctioning subendocardial myocardial helix. Increased PBR was related with impaired deformation markers at baseline and 120min of OGTT (p<0.05).
  
  
  CONCLUSIONS
  First-degree relatives and dysglycaemics have reduced glycocalyx thickness related with impaired LV longitudinal, twisting-untwisting function. Postprandial hyperglycemia when combined with insulin resistance causes LV longitudinal dysfunction leading to increased LV twisting.
authors.affiliation: 2nd Cardiology Department, Attikon Hospital, National and Kapodistrian University of Athens, Medical School, Greece. Electronic address: ignoik@otenet.gr.
authors.forename: Ignatios
authors.initials: I
authors.lastname: Ikonomidis
authors.affiliation: 2nd Cardiology Department, Attikon Hospital, National and Kapodistrian University of Athens, Medical School, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Pavlidis
authors.affiliation: 2nd Department of Internal medicine, Research Unit and Diabetes Centre, Attikon Hospital, National and Kapodistrian University of Athens, Medical School, Greece.
authors.forename: Vaia
authors.initials: V
authors.lastname: Lambadiari
authors.affiliation: 2nd Department of Internal medicine, Research Unit and Diabetes Centre, Attikon Hospital, National and Kapodistrian University of Athens, Medical School, Greece.
authors.forename: Fotini
authors.initials: F
authors.lastname: Kousathana
authors.affiliation: 2nd Cardiology Department, Attikon Hospital, National and Kapodistrian University of Athens, Medical School, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Varoudi
authors.affiliation: 2nd Department of Internal medicine, Research Unit and Diabetes Centre, Attikon Hospital, National and Kapodistrian University of Athens, Medical School, 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, National and Kapodistrian University of Athens, Medical School, Greece.
authors.forename: John
authors.initials: J
authors.lastname: Parissis
authors.affiliation: 2nd Cardiology Department, Attikon Hospital, National and Kapodistrian University of Athens, Medical School, Greece.
authors.forename: Helen
authors.initials: H
authors.lastname: Triantafyllidi
authors.affiliation: 2nd Department of Internal medicine, Research Unit and Diabetes Centre, Attikon Hospital, National and Kapodistrian University of Athens, Medical School, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Dimitriadis
authors.affiliation: 2nd Cardiology Department, Attikon Hospital, National and Kapodistrian University of Athens, Medical School, Greece.
authors.forename: John
authors.initials: J
authors.lastname: Lekakis
mesh_terms: D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D042241:Early Diagnosis; D004452:Echocardiography / Q000379:methods*; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000503:physiopathology; D005190:Family; D005260:Female; D019276:Glycocalyx / Q000378:metabolism*; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000503:physiopathology; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D016277:Ventricular Function, Left / Q000502:physiology
keywords: Diabetes; First degree relatives; Insulin resistance; LV myocardial strain; LV twisting and untwisting