Changes in endothelial glycocalyx, elastic properties of arteries and coronary flow reserve during oral glucose tolerance test in dysglycaemics and first degree relatives of diabetic patients

Doctoral Dissertation uoadl:1722843 305 Read counter

Unit:
Τομέας Παθολογίας
Library of the School of Health Sciences
Deposit date:
2017-07-18
Year:
2017
Author:
Pavlidis Georgios
Dissertation committee:
Γεώργιος Δημητριάδης, Καθηγητής Παθολογίας, Ιατρική Σχολή ,ΕΚΠΑ
Ιωάννης Λεκάκης, Καθηγητής Καρδιολογίας, Ιατρική Σχολή, ΕΚΠΑ
Ευστάθιος Ηλιοδρομίτης, Καθηγητής Καρδιολογίας, Ιατρική Σχολή, ΕΚΠΑ
Ιγνάτιος Οικονομίδης, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Χατζηαγγελάκη Ερυφίλη, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Παρίσης Ιωάννης, Αναπληρωτής Καθηγητής, Ιατρική Σχολή ,ΕΚΠΑ
Βάια Λαμπαδιάρη, Επίκουρη Καθηγήτρια, Ιατρική Σχολή ,ΕΚΠΑ
Original Title:
Μελέτη των μεταβολών του ενδοθηλιακού γλυκοκάλυκα, των ελαστικών ιδιοτήτων των αρτηριών και της στεφανιαίας εφεδρείας ροής σε συγγενείς πρώτου βαθμού ασθενών με σακχαρώδη διαβήτη
Languages:
Greek
Translated title:
Changes in endothelial glycocalyx, elastic properties of arteries and coronary flow reserve during oral glucose tolerance test in dysglycaemics and first degree relatives of diabetic patients
Summary:
Introduction: Insulin resistance is linked to endothelial dysfunction. We investigated whether first - degree relatives of type-2 diabetes patients (FDR) present differences in vascular function, glycocalyx thickness and LV deformation 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 (AIx) were measured at 0, 30, 60, 90 and 120min during OGTT. At 0 and 120min of OGTT we measured: a) Coronary flow reserve (CFR) was assessed using Doppler echocardiography b) LV longitudinal strain (LS) of subendocardial, mid-myocardial and subepicardial layers, global LS (GLS), peak twisting (pTw), twisting (pTwVel) and untwisting velocity (pUtwVel), by speckle tracking echocardiography c) perfused boundary region (PBR) of the sublingual arterial microvessels; high PBR values represent reduced glycocalyx thickness. Insulin sensitivity was evaluated using Matsuda and insulin sensitivity index (ISI).
Results: FDR and dysglycaemics had higher fasting insulin and PBR, reduced ISI, Matsuda index as well as reduced CFR (2.54 ± 0.5 vs. 2.45 ± 0.3 vs. 2.74 ± 0.5), 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 ± 6.5 deg) and pUtwVel and increased PWV (8.9 ± 1.1 vs. 10.3±2.4 vs. 8.0 ± 1.5 m/sec), AIx (23.8 ± 13.6 vs. 26.5 ± 14.4 vs.17.7 ± 14%) and cSBP than normoglycaemics (p < 0.05 for all comparisons). During OGTT, AIx 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. AIx was increased in dysglycaemics after peak glucose levels, at 120 min (p < 0.05). CFR was reduced by 10% and 15% at 120 min 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). ISI was related with baseline PBR, GLS and pTw in all subjects (p < 0.05). Compared to baseline, GLS and the sudendocardial LS decreased while pTw, pTwVel, pUtwVel increased in FDR and dysglycaemics post - OGTT (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 0 and 120 min of OGTT (p < 0.05).
Conclusions: First - degree relatives and dysglycaemic patients have impaired arterial and coronary microcirculatory function and reduced glycocalyx thickness related with impaired LV longitudinal, twisting - untwisting function. Insulin resistance determines acute vascular responses during postprandial hyperglycemia. Postprandial hyperglycemia when combined with insulin resistance causes LV longitudinal dysfunction leading to increased LV twisting.
Main subject category:
Health Sciences
Keywords:
Arterial stiffness, Endothelial glycocalyx, Coronary circulation, Insulin resistance, First degree relatives, Diabetes
Index:
No
Number of index pages:
0
Contains images:
Yes
Number of references:
409
Number of pages:
235
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