Advancing automated insulin delivery for exercise to improve the daily lives of people with type 1 diabetes

All procedures involving study participants will be undertaken by study doctors, nurses and scientists. Participants will be directly supervised by research personnel for all study activities in the clinical trial centre (CTC), including exercise. Maximal cardiopulmonary exercise testing (VO2max) will be assessed on a stationary bicycle over 15 min. Maximal strength (3-lift max) will be measured. Participants will be provided with study devices and receive education regarding their use. Transcutaneous glucose sensors will be worn for continuous glucose monitoring (CGM) during the study. A study insulin pump will be programmed with the participant’s individualised insulin delivery settings and paired with the CGM. Participants will undertake three exercise stages in random order, separated by 1–4 weeks (timing determined by participant availability). The exercise intervention bouts within the respective stages are: (i) moderate-intensity exercise (MIE) on a stationary bicycle [32 min continuous exercise at 40% maximal intensity]; (ii) high-intensity interval exercise (HIIE) on a stationary bicycle [4 × 4 min intervals at 80% maximal intensity with 4 min rest between intervals]; and (iii) resistance exercise (RE) involving a circuit of five compound resistance exercises (e.g. leg press, seated row) each performed for 8-12 repetitions and completed 3 times (resistance weight at 80% 3–lift max). Four days prior to each exercise bout, closed loop (CL) automated insulin delivery mode will be initiated on the insulin pump. Prior to each exercise bout, participants will eat a standardised lunch (with 40 g carbohydrate, 25 g protein and 10 g fat) at midday, then attend the CTC early afternoon. Accelerometers (wrist and ankle) and electrocardiogram leads will be attached, and an intravenous cannula will be inserted for sample collection. During the HIIE stage only, a prototype lactate sensor will be inserted subcutaneously in the anterior abdomen and attached to a recorder. Two hours prior to each exercise bout, the CL glucose target will be increased from 6.7 mmol/L to 8.3 mmol/L. Exercise will commence 4 h after the standardised lunch. If blood glucose is <7.0 mmol/L at 10 min pre-exercise, 15 g carbohydrate will be consumed. Ten min after exercise completion, the CL target will be decreased to 6.7 mmol/L. Non-arterialised venous samples will be collected at standardised intervals (starting 60 min pre-exercise and finishing 240 min post-exercise completion) for measurement of glucose, lactate, ketones, free insulin, adrenaline, noradrenaline, dopamine, cortisol, growth hormone and glucagon. Blood ketones will continue to be measured hourly until they are <0.4 mmol/L. A standardised meal (with 45 g carbohydrate, 30 g protein and 15 g fat) will be provided for consumption at 21:00 h, preceded by an insulin bolus as per participants’ usual individualised settings. After the meal, the intravenous cannula and accelerometers will be removed and the participant will depart the CTC. Participants will continue using CL for 6 days after each exercise bout. CGM data will be recorded throughout the study. Heart rate will be monitored by electrocardiograph from 30 min before exercise until 60 min after exercise completion. Accelerometer data will be recorded during the CTC visit and downloaded after wear.