The effects of relative hyperglycemia on neurovascular coupling magnitude in healthy participants: Impact of biological sex

Neurovascular coupling (NVC) is a process that ensures adequate blood flow to brain regions with higher metabolic demands, and is one of several mechanisms in place to maintain cerebral blood flow (CBF) and support neuronal homeostasis. Previous research demonstrated the robustness of NVC responses to blood gas challenges. However, other studies found attenuation in NVC responses in individuals with metabolic disorders, and there are well-documented differences in glucose metabolism between males and females. We investigated NVC responses before and after acute oral glucose ingestion, including possible sex-specific differences in healthy males and females. We recruited 36 participants (18 males:18 females) and used transcranial Doppler ultrasound to measure (a) resting cerebral blood velocity (CBV) in the posterior cerebral artery (PCAv) and (a) NVC responses using a series of five visual stimuli (VS) trials (360rpm/6Hz strobe light). Testing occurred before (fasted; FAST) and 30-min after participants ingested a standard 75g/300ml oral glucose drink (glucose loaded; GL) to elicit acute relative hyperglycemia, confirmed via capillary blood sample and glucometer (FAST:4.79±0.36mmol/L; GL:7.55±1.23mmol/L; p<0.0001). We then compared measures of PCAv at rest and during VS to evaluate any sex-specific differences in NVC between FAST and GL states. GL increased baseline PCAv (P=0.005), but this baseline elevation did not affect the dynamic peak NVC response, as evidenced by no changes in metrics of peak responses during the VS post GL (Delta peak: P=0.591; Time-to-peak: P=0.124; Slope: P=0.864). However, the NVC trials resulted in decreased delta mean responses post-GL compared to FAST (P=0.001). When comparing sexes, these responses were observed in males only, with increased baseline PCAv in GL compared to FAST (males:P=0.004; females:P=0.233). This increased baseline CBV resulted in a decreased delta mean NVC responses in males (P=0.002), but not in females (P=0.100). This study adds to the growing body of literature highlighting the stability of peak NVC responses in healthy humans, and demonstrates novel sex-specific baseline CBV and mean NVC responses in acute relative hyperglycemia. In male participants only, we observed an increase in baseline CBV and an attenuated mean NVC response in GL, due to the increased baseline CBV. This work points to future opportunities to explore the acute and chronic effects of clinical hyperglycemia on NVC between sexes. Natural Sciences and Engineering Research Council of Canada (TAD, RGPIN-2016-04915) This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.