A CFit Study - Acute Exercise

Overview

A great medical success is the increase in the median survival age associated with cystic fibrosis (CF). However, this success has led to a new era of research aiming to maximise the quality of life (QoL) of the aging CF population. Over recent decades, exercise training has become an integral part of CF management by improving ones aerobic exercise function and QoL. However, the effects exercise training has upon other aspects of the disease, e.g. metabolic and vascular abnormalities, remains largely unknown. The increased survival age associated with CF means the non-pulmonary co-morbidities are becoming increasingly prevalent and clinically important. For example, CF-related diabetes (CFRD) is one of the most common non-pulmonary co-morbidities of CF, and is associated with patients having a poorer pulmonary function and nutritional state, which ultimately leads to a worsened prognosis. Despite the efficacy of exercise training to manage dysglycaemia in other populations (e.g. type 2 diabetes mellitus only a single study has investigated its efficacy in patients with CF, whereby authors reported various encouraging findings (e.g. an improved OGTT score and insulin sensitivity). The present study aims to build on previous trials by comparing the therapeutic effects of a single session of high-intensity interval exercise (HIIE) and moderate intensity exercise (MIE) upon the 24 hour, ambulatory glycaemic profile of patients with CF. Additionally, the present study will identify whether HIIE and/or MIE can mediate the consequences of transient hyperglycaemia when considering: biomarkers of inflammation, oxidative stress and nitric oxide (NO2) bioavailability, as well as functional measures of microvascular endothelial function. The present study supports the top 10 research priorities set by the CF Trust, by further investigating the potential for exercise training to prevent/manage multiple aspects of CF, including dysglycaemia.

Participants and recruitment The present study will be a pilot, counter-balanced, cross-over trial in individuals with CF (n = 16). Furthermore, the present protocol is an extension of the CFit\_BL protocol (Clinical Trials ID to be confirmed). Specifically, 16 participants with CF will be invited to complete 2 visits (5 in total) within the same 14 day time period. Briefly, participants will be recruited from adult and paediatric CF outpatient clinics within the Southampton CF network, and will be tested at a laboratory within the Southampton General Hospital or the Department of Sport and Exercise Sciences (University of Portsmouth), depending on participant convenience. The present study will comprise 2 visits which will be in a randomised, counter-balanced order. Visits 1 and 2 A session of moderate intensity exercise (MIE) training and high-intensity interval exercise (HIIE) training visit will be conducted in a randomised, counter-balanced order. Participants will be required to arrive to the laboratory \~ 96 hours following the previous visit, at 0800 ± 2 hours, following an overnight fast (\> 10 hours). Furthermore, participants will be instructed to avoid nitrate rich foods, caffeine, alcohol and exhaustive exercise for 24 hours prior to arrival, as well as mouthwash for the entirety of the study. Upon arrival, CGM's will be fixed to the interior surface of the upper arm and worn for the subsequent 14 days. In addition to this, hip worn accelerometers, as well as hourly specific physical activity and food diaries will be distributed and completed for 14 days alongside the CGM. Upon arrival participants will undergo the acetylcholine (ACh) and insulin iontophoresis protocols described below, including 5 resting blood pressure measurements and a cannula will be inserted into a vein by a trained phlebotomist, prior to the 3 hour OGTT and a baseline blood sample will be taken. The participant's pulmonary function will be assessed via spirometry. Participants will then be asked to complete either a single session of either MIE or HIIE. Pulmonary function will then be assessed immediately post-exercise. 1 hour following exercise, the iontophoresis procedures will be repeated. Blood samples will be drawn immediately pre- and post-exercise for the analysis of plasma TNF-α, soluble vascular cell adhesion molecule (sVCAM)-1, IL-6, \[NO-(₂)\] and ET-1. Samples for nitrotyrosine (NT), total glutathione (tGSH) and total cysteine (tCys) will be drawn pre-exercise only. Subsequently, participants will partake in either 30 minutes of MIE or a work-matched period of HIIE. Thirty minutes following the completion of the exercising procedures, the iontophoresis procedures will be repeated and blood samples will be drawn for the analysis of plasma glucose, insulin, TNF-α, sVCAM-1, IL-6, \[NO-(₂)\] and ET-1. NT, tGSH and tCys. Following this, 1.75 g/kg body mass (maximum of 75 g) of anhydrous glucose will be consumed to instigate the 3 hour OGTT, whereby blood samples will be drawn at 30, 60, 90, 120 and 180 minutes post-glucose ingestion for the analysis of glucose and insulin. Samples for TNF-α, sVCAM-1, IL-6, \[NO-(₂)\] and ET-1 will be drawn at 60, 120 and 180 minutes post-glucose ingestion. NT, tGSH and tCys will be analysed at 120 minutes post-glucose ingestion. The total volume of blood collected over each 5 hour visit will be approximately 232 mL. Additionally, the iontophoresis procedures will be repeated at 30, 90 and 150 minutes post-glucose ingestion. Follow-up CGM's, accelerometers and physical activity/food diaries will be completed throughout this 14 day period. A member of the research team will collect these from the preferred location of the participant.