The Glycocalyx and Associated Microvasculature as a Marker of Adverse Pregnancy Outcome in Women with Pre-existing Diabetes Mellitus

Abstract

Introduction: The chronic hyperglycaemic conditions of type 1 (T1DM) and type 2 (T2DM) diabetes mellitus adversely affect the endothelial glycocalyx (GLx) and the associated microvasculature. Degradation of the GLx and reduced microvascular perfusion are features of many adverse pregnancy outcomes (APOs) associated with pre-existing diabetes (PDM). The aim of this thesis was to reliably establish the course of the GLx and microvascular perfusion antenatally and postnatally in PDM and NG pregnancies. Using this information, it may be possible to identify PDM pregnancies that go on to develop later APOs.
Methods: A prospective longitudinal cohort study enrolled pregnant women with T1DM and T2DM and normoglycaemic (NG) controls. Repeated measurements of the GLx and microvascular perfusion were performed noninvasively using sublingual side-stream dark field imaging with GlycoCheckTM. In addition to this, measurements of maternal circulating syndecan-1 and syndecan-4, biomarkers of the GLx, were quantified ex vivo using ELISA. Statistical analysis included multi-level modelling. Reliability was established prior to data collection.

Results: Novel antenatal trajectories and postnatal courses in PDM (n=47) and NG (n=65) pregnancies were calculated from measurements of the GLx and microvascular perfusion. T1DM pregnancies (n=32) were observed to have a statistically significant reduced GLx thickness of 32m, 32 [mean] days before being diagnosed with pre-eclampsia compared to other T1DM pregnancies (p=0.04). Other markers of GLx degradation and reduced microvascular perfusion are reliably and consistently present, although not reaching statistical significance, in the systemic circulation from the 1st trimester onwards.

Conclusion: Novel antenatal GLx trajectories have been reliably established for the first time. There is also statistically significant evidence of a degraded GLx dimension being predictive of pre-eclampsia in T1DM pregnancies compared to other T1DM pregnancies. There are also consistent trends, apparent from the 1st trimester onwards which, with larger-scale and pre-pregnancy research, may yield valuable new ways of identifying at-risk PDM pregnancies at an earlier stage than is currently clinically possible.

Date of Award	5 Dec 2023
Original language	English
Awarding Institution	University of Bristol
Supervisor	Simon C Satchell (Supervisor), Victoria L Bills (Supervisor), R R Foster (Supervisor) & Abigail Fraser (Supervisor)