Interrupting prolonged sitting with intermittent physical activity in adults with abnormal glucose metabolism : Effects on vascular function

Sedentary behaviours, defined as waking behaviours undertaken in a sitting/lying posture with low energy expenditure (i.e., ≤ 1.5 metabolic equivalent of tasks [METS]), are now recognised as being strongly associated with all-cause and cardiovascular disease (CVD)-related mortality. Specifically, acute experimental studies have reported prolonged uninterrupted sitting to exacerbate postprandial cardiometabolic risk biomarkers [1] and decrease vasodilatory function [2-4] People with abnormal glucose metabolism (which refers to a combination of clinical disorders that increase the risk for diabetes and cardiovascular disease) are disproportionally affected by the risks associated with prolonged uninterrupted sitting, owing partly to vascular dysfunction and consequent predisposition to atherosclerosis.

Lifestyle modification remains a cornerstone treatment for the prevention and management of CVD, and recent World Health Organization (WHO) guidelines have been expanded to include a recommendation to reduce and regularly replace sedentary time (sedentary behaviour) with activity. Despite this, relatively little is known about the effects of prolonged sitting on vascular function in those with abnormal glucose metabolism. Additionally, it is currently unknown whether reducing and interrupting sitting time with activity positively influences vascular function in these population groups. The primary aim of this Thesis was to examine the extent and nature of vascular impairment in response to prolonged sitting across the abnormal glucose spectrum; with a focus on reducing and interrupting time spent sitting with activity in clinical populations.

Study 1 aimed to determine the dose-response relationship between acute prolonged uninterrupted sitting and vascular function through a systematic review and meta-analysis. Additional sub-group analyses examined the effect of prolonged sitting in healthy adults relative to those with abnormal glucose metabolism. A secondary aim was to compare the acute effects of uninterrupted prolonged sitting to interventions involving acute light activity interruptions. The findings revealed that lower-limb vascular function is progressively impaired as time spent in prolonged sitting increases. Moreover, it was observed that prolonged sitting decreased lower-limb vascular function in healthy adults, who had higher a priori vascular function, but not in those with metabolic and vascular dysfunction. However, the limited number of studies in those with abnormal glucose metabolism make it difficult to draw conclusive findings. Additionally, while interrupting sitting with brief bouts of physical activity improved vascular function, considerable heterogeneity was reported between trials, likely due to differing experimental design (mode, frequency, and duration of breaks).

Study 2 compared the acute effects of interrupting sitting with two different activity protocols of equivalent activity duration on vascular function in a clinical population with abnormal glucose metabolism - those with type two diabetes (T2D). Femoral flow-mediated dilation (FMD) averaged across 7h significantly increased when prolonged sitting was interrupted with 3 min of SRAs every 30 min. However, relative to prolonged sitting, interrupting sitting every 60 min with 6 min simple resistance activities (SRAs) did not result in significant changes in vascular function. Vascular shear rate and blood flow were also enhanced by interrupting sitting with SRAs, regardless of frequency. These findings suggest that more frequent, shorter interruptions may be more beneficial than longer, less frequent breaks for vascular improvement in those with T2D. Further, the study provides new insights into the frequency and duration of activity breaks that may be required to improve vascular function during prolonged sitting.

In addition to identifying a lack of studies assessing vascular function and sedentary behaviour in populations with metabolic dysfunction, study 2 also reported a lack of female participants in the trials conducted to date. Study 3 sought to address this gap by examining the effect of prolonged uninterrupted sitting on femoral vascular function in young women with polycystic ovary syndrome (PCOS). Relative to 3.5h prolonged sitting, interrupting sitting with 3 min of SRAs every 30 min significantly increased mean femoral resting shear and blood flow. However, no change was observed in FMD between conditions.

Collectively, this Thesis has contributed new knowledge to the sedentary behaviour and vascular function research field, specifically: by 1) highlighting the progressive impairment of lower-limb vascular function in response to prolonged uninterrupted sitting; 2) demonstrating that interrupting prolonged sitting with more frequent and shorter activity breaks may be more beneficial than longer, less frequent breaks, for vascular health, in those with T2D, and 3) demonstrating that interrupting prolonged sitting with activity breaks improves blood flow and shear rate for women with PCOS. Future research could build on these findings to focus on three key areas:

1. Obtaining a greater understanding of how vascular function changes over time in response to prolonged sitting. This includes free-living and longer-term studies, in addition to acute studies that measure vascular function at multiple time points across the day.
2. Assessing varying modes, duration, and frequency of interruptions in prolonged sitting to identify optimum activity interruptions.
3. Inclusion of female participants and older and clinical populations into clinical trials to enhance the generalisability of public health recommendations.