The Impact of Exercise on the Performance of an Artificial Pancreas in Type 1 Diabetes and Impaired Awareness of Hypoglycaemia

INTERVENTION: This is a two‐stage randomised crossover study involving adults with type 1 diabetes and impaired awareness of hypoglycaemia who are established on insulin pump therapy and have glucose sensing experience. The study aims to examine the performance of an ‘artificial pancreas’ or hybrid closed‐loop (HCL) insulin delivery system challenged by high intensity intermittent exercise (HIIE) and moderate intensity exercise (MIE) in people with type 1 diabetes and impaired awareness of hypoglycaemia. Previous studies have shown that the HCL system is safe for people with type 1 diabetes undertaking HIIE (anaerobic) and MIE (aerobic). However, this has not been assessed in the group with impaired awareness of hypoglycaemia. Potential participants will be identified using a validated questionnaire (Gold questionnaire) to assess their degree of hypoglycaemia unawareness. A Gold score of 4 or greater implies impaired awareness of hypoglycaemia. All participants will use the HCL system for the study duration. Education specific to the HCL study system will be provided face‐to‐face by an experienced study doctor and a diabetes nurse educator, and will be tailored to each participant’s prior knowledge. Participants will also be provided educational material and resources, including a user guide booklet for the investigational HCL system. The HCL system comprises a glucose sensor coupled with an insulin pump containing a computerised automated insulin delivery algorithm. Glucose sensor information is transmitted to the insulin pump, and the dose of insulin is calculated by the algorithm and delivered every 5 minutes to account for basal insulin requirements. Participant initiated bolus insulin doses are still required for meals. Following clinical assessment, each participant will undergo cardiopulmonary testing to determine their maximal amount of oxygen consumed during exercise (VO2 max as ml/kg/min), maximal exercise capacity (Watts) and anaerobic threshold. All participants will undertake the HIIE and MIE stages in random order. All exercise testing will be closely supervised at all times by both a qualified study doctor and a nurse with dual training in research coordination and diabetes education. Approximately 1 week after activation of the HCL system, participants will undertake their first exercise stage. They will then return 1 week later to undertake the alternate exercise regimen. All exercise testing will be conducted in the late morning, at least 4 hours after breakfast is consumed. The MIE protocol will be conducted on a stationary bicycle with 5 minutes of warm‐up, followed by 40 minutes of steady‐state exercise at 70% of anaerobic threshold. The HIIE protocol is high intensity interval training with 5 minutes of warm���up, then 6 repetitions of 4 minutes of exercise at an intensity halfway between their anaerobic threshold and maximal intensity, followed by 2 minutes of rest (an additional 4 minutes rest will be provided between the 3rd and 4th repetitions). On the morning of the exercise study days, participants will have an early morning light breakfast (40g of carbohydrate), preceded by an insulin bolus via their own pump to account for the carbohydrate of the meal. The participants will commence their exercise program Participants will return one week following the second exercise stage to return study devices and resume their usual insulin delivery system. CONDITION: Hypoglycaemia Type 1 Diabetes PRIMARY OUTCOME: Continuous glucose monitoring (CGM) % time spent in target glucose range (3.9–10mmol/L) for each exercise stage. ; 1. High‐intensity intermittent exercise ; 2. Moderate‐intensity exercise ; Episodes of hyperglycaemia (>10.0mmol/L) and blood ketones >0.6 mmol/L as reported by the participant (composite secondary outcome) 2 hours after arrival at the Clinical Trial Centre, at which time the ‘exercise mode’ of the HCL system will be activated. Venous blood samples will be collected at 15 minute intervals from 1 hour prior to exercise until 2 hours after exercise completion to assess insulin and counter‐regulatory hormones. SECONDARY OUTCOME: Differences in peak counter‐regulatory hormone levels measured using serum assays for catecholamines, glucagon, growth hormone, cortisol, lactate, ketones during hybrid closed‐loop therapy for: ; Episodes of major hypoglycaemia (defined as any low glucose level requiring the assistance of another person to actively administer carbohydrate, glucagon or take other corrective actions) as reported by the participant Episodes of symptomatic hypoglycaemia (the presence of typical symptoms of hypoglycaemia accompanied by a measured finger‐prick glucose level <3.9mmol/l) as reported by the participant Glycaemic outcomes 24 hours post exercise commencement ; 1.1. % CGM time 3.9–10mmol/L (excluding the primary endpoint) ; 1.2. % CGM time 3.9–8.0mmol/L ; 1.3. % CGM time <3.9 mmol/L ; 1.4. % CGM time <3.5 mmol/L ; 1.5. % CGM time <3.0 mmol/L ; 1.6. % CGM time <2.8 mmol/L ; 1.7. % CGM time >10.0 mmol/L ; 1.8 Glycaemia Variability as determined by mean amplitude of glycaemic excursions (MAGE) and standard deviation ; 1.9 CGM AUC > 10.0 mmol/L ; 1.10 CGM AUC <3.9 mmol/L ; Glycaemic outcomes for the night following exercise [0:00‐08:00] ; 1.1 % CGM time 3.9–10mmol/L (excluding the primary endpoint) ; 1.2 % CGM time 3.9–8.0mmol/L ; 1.3 % CGM time <3.9 mmol/L ; 1.4 % CGM time <3.5 mmol/L ; 1.5 % CGM time <3.0 mmol/L ; 1.6 % CGM time <2.8 mmol/L ; 1.7 % CGM time >10.0 mmol/L ; 1.8 Glycaemia Variability as determined by mean amplitude of glycaemic excursions (MAGE) and standard deviation ; 1.9 CGM AUC > 10.0 mmol/L ; 1.10 CGM AUC <3.9 mmol/L ; Glycaemic outcomes from time of exercise commencement until 2 hours post‐exercise completion ; 1.1 % CGM time 3.9–10mmol/L (excluding the primary endpoint) ; 1.2 % CGM time 3.9–8.0mmol/L ; 1.3 % CGM time <3.9 mmol/L ; 1.4 % CGM time <3.5 mmol/L ; 1.5 % CGM time <3.0 mmol/L ; 1.6 % CGM time <2.8 mmol/L ; 1.7 % CGM time >10.0 mmol/L ; 1.8 Glycaemia Variability as determined by mean amplitude of glycaemic excursions (MAGE) and standard deviation ; 1.9 CGM AUC > 10.0 mmol/L ; 1.10 CGM AUC <3.9 mmol/L ; Number of episodes of hypoglycaemia (glucose levels < 3.9mmol/L) using CGM data uploaded from the HCL study pump ; Number of episodes of hypoglycaemia (glucose levels < 3.9mmol/L) using CGM data uploaded from the HCL study pump Number of unscheduled exits from closed‐loop system using CGM data uploaded from the HCL study pump. Total number of episodes of hypoglycaemia (glucose levels <3.9mmol/L) whilst using the hybrid closed‐loop system INCLUSION CRITERIA: 1. Type 1 diabetes 2. Established on insulin pump therapy for at least 6 months 3. Sensor experience 4. HbA1c < 10.0% 5. GOLD score >=4 6. Ability to perform exercise as per protocol