What is the central question of the study? This is the first study to examine the impact of acute hyperglycaemia on endothelial function [flow-mediated dilatation (FMD)] in premenopausal women across the early and late follicular (EF and LF) phases of the menstrual cycle. What is the main finding and its importance? Flow-mediated dilatation was impaired 90 min after glucose ingestion, with no significant difference between phases. This indicates that women are susceptible to acute hyperglycaemia-induced endothelial dysfunction in both the EF and LF phases of the menstrual cycle, despite potentially vasoprotective elevations in estradiol levels during the LF phase. Acute hyperglycaemia transiently impairs endothelial function in healthy men when assessed via flow-mediated dilatation (FMD). However, research in female participants is lacking, and the impact of menstrual phase [early follicular (EF) and late follicular (LF)] on vulnerability to acute hyperglycaemia-induced endothelial dysfunction is unknown. Seventeen healthy, naturally menstruating women [21±1 years old (mean ± SD)] participated in three visits. During two visits (EFGlucose and LFGlucose ), brachial artery FMD was assessed before and 60, 90 and 120min after an oral glucose challenge (75g glucose). During an additional EF visit, participants ingested 300ml of water (EFTimeControl ). Blood glucose and insulin increased 30 min after glucose ingestion (P<0.001), with no difference between phases. Flow-mediated dilatation did not change in EFTimeControl (P=0.748) but was reduced 90min after glucose ingestion (Pre, 8.5±2.5%; Post90, 6.6±2.4%, P=0.001; Cohen's d=0.82), with no difference between phases (main effect of phase, P=0.506; phase by time interaction, P=0.391). To account for individual variability in the time course of the impact of hyperglycaemia, the maximal hyperglycaemia-induced impairment in FMD was determined in each participant and compared between phases, revealing no significant phase differences (EFGlucose , -3.1±2.8%; LFGlucose , -2.4±2.1%, P=0.181; d=0.34). These results indicate that, similar to findings in men, acute hyperglycaemia results in FMD impairment in young women. We did not detect significant protection from acute hyperglycaemia-induced endothelial dysfunction in the LF 'high-oestrogen' phase in this sample, and further research is needed to examine the potential for a protective effect of oestrogen exposure, including oral contraceptive pills and hormone replacement therapy.
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