Optimisation of Exercise Intensity During High-Intensity Interval Training for Glucose Control in Prediabetes

Recruitment Recruitment 12 men will be recruited through Church and Borth GP Surgeries in Aberystwyth. Patients attending GP appointments who are considered to be at risk of developing diabetes will have a blood sample taken as part of usual care, this sample will be analysed for HbA1c. If the HbA1c value is between 42 and 47 mmol·mol-1 the patient is considered to be prediabetic. Usual care for this group would be to inform the newly diagnosed patient by letter of the test result and provide information on diet and exercise to reduce the risk of developing T2DM. Patients who have had an HbA1c value of between 42 and 47 mmol·mol-1 during the previous 12 months will be identified by the surgery who will then contact the patient by post with details of the study, including contact information for the research team. The research team will have no contact with the patient unless they make contact to request more information. Additionally, posters will be placed around Aberystwyth University campus, Aberystwyth town, and an email will be sent to IBERS and university staff, as well as using social media networks including the WARU (https://waru.org.uk/cms/) Facebook and Twitter accounts. Potential participants, not recruited through their GP surgery, but who have been diagnosed with prediabetes can contact the research team to express their interest.

Following contact expressing an interest in participation, the research team will provide the individual with the participant information sheet via email or post. If having received, and read, the participant information the individual is still interested in becoming involved in the study there contact details will also be passed onto the Cardiology Department of Bronglais General Hospital. Consent will be obtained prior to contact information being shared. An appointment will then be arranged between the cardiologist and participant for the first visit, the chief investigator will also attend this first visit.

Visit One On arrival at the local hospital, participants will be given a detailed verbal explanation of the study protocol by the chief investigator, which will explain the purpose of the study and explicitly state what is required of them. The participant will also have the opportunity to ask questions about the study and will be informed of their right to withdraw without the need of an explanation. They will then give written informed consent to participate in the study. Once consent has been given, participants will then be asked to complete a health screening questionnaire. Following this, the participant will complete an exercise stress test with continuous electrocardiogram (ECG) monitoring, using the 'Bruce protocol', which will be examined for an indication of cardiovascular disease. If the participant is excluded from the study based on their ECG results, they will be informed by the cardiologist who will then inform their GP. If the participant is not excluded at this stage, a date and time for the second visit will be arranged.

Visit Two On arrival the participant will be given the opportunity to ask for clarification on any aspect of the study and their involvement, they will also be reminded of the right to withdraw from the study. The participant will sit for 10 minutes before blood pressure (Omron M2 Basic, Automatic Blood Pressure Monitor, Milton Keynes, UK) height (Harpenden Stadiometer, Holtain Ltd; Crymych, UK) body mass (Tanita, Body Composition Analyzer, DC-430MA, Amsterdam, Netherlands) and waist circumference (Rollfix, Hoechstmass, West Germany) are recorded and Body Mass Index (BMI) calculated. A fingertip blood sample will be taken and analysed for glycated hemoglobin (HbA1c) and blood lipid profile (Alere Afinion AS100, Abbott, Cheshire, UK). Participants will then complete a maximal exercise test which will involve completion of a 'ramp' test performed on a cycle ergometer (Lode Excaliber sport V2, Lode BV, Gronigen, Netherlands) to determine VO2peak and Gas Exchange Threshold (GET). The ergometer will be adjusted so that each subject is comfortable, and the settings will be recorded and replicated during all subsequent exercise tests. The test will involve three minutes of pedaling at 0 W, followed by a continuous ramped increase in work rate of 15 W·min-1. Participants will be instructed to maintain a cadence of 65 ± 5 r.p.m. throughout the test. When the participant can no longer maintain ≥ 55 r.p.m., despite verbal encouragement, the test will be terminated. Throughout the test, heart rate (HR) will be recorded via short wave telemetry (Polar, S610i, Kempele, Finland). Pulmonary gas exchange and ventilation will be measured breath-by-breath, (COSMED Quark CPET, COSMED srl, Rome; Italy). The gas analysers will be calibrated before each test with gases of known concentration, and the turbine volume transducer will be calibrated using a three-liter syringe. VO2peak will be determined as the highest VO2 measured over 30 seconds and GET will be determined using the V-slope method (Beaver et al. 1986) as the first disproportionate increase in carbon dioxide output (VCO2) relative to VO2. The work rate corresponding to 105% of VO2peak, and 50%∆ of GET, which is 50% of the difference between GET and VO2peak, will be calculated using linear regression of VO2 versus work rate with account taken of the lag in VO2 relative to work rate that exists during ramp incremental exercise (Whipp et al. 1981). On the completion of exercise, the participants will be provided with a menu from which they will choose five meals (two breakfasts, one lunch and two dinners) to eat prior to and following each of the three experimental trials.

Finally, participants will be given an ActiGraph activity tracker and instructions on its use. The tracker will be worn by the participant for a two and a half day period during each of the three experimental trials; the day before a trial from waking, the day of the trial until retiring to bed, and the day following the trial from waking until two-hour post second carbohydrate (CHO) load.