Assessing the impact of exercise timing on glycaemic control

Study Design: Potential participants will be initially be screened by the study coordinator. Participants will then be invited to attend the Exercise Physiology Clinic at Murdoch University for the collection of preliminary measurements and baseline data following attainment of written informed consent. Following baseline assessments, participants will be randomly assigned into their intervention groups (POSTam and POSTpm) to begin their 12-week exercise training intervention. Mid-intervention assessments will occur during Week 6 to assess: (i) glycaemic control and; (ii) aerobic fitness. At least 24 hours after the last training session in Week 12, but no more than 96 hours after the last training session, participants will then complete their final assessment of glycaemic control and aerobic fitness. Procedures: Participants will continue their medications at the usual dose, frequency and time while participating in this study. Baseline testing will include body anthropometrics (dual energy X-ray absorptiometry [DXA], height, weight and waist circumference), aerobic fitness assessment (VO2 peak test; modified Bruce treadmill test protocol), diet history (24h dietary recall conducted on 5 separate occasions representing different days), 14-day sleep and physical activity monitoring (Actigraph and diary), 24 h skin temperature (iButton, data logger) and an appetite questionnaire. Additionally, participants will attend the laboratory (study day) for assessment of postprandial glucose changes (in response to a oral glucose tolerance test; OGTT) and changes in fasting glucose and insulin along with measures of peripheral insulin sensitivity derived during the OGTT (Cederholm index). The OGTT (75g) will be performed in the morning, following an overnight fast. One blood sample will be taken prior to the ingestion of the glucose solution (Trutol) for measures of glycaemic control (HbA1c; 1,5-anhydroglucitol [1,5-AG]). Thereafter, samples will be taken every 15min via a venous canula for the duration of the 2-h OGTT for changes in postprandial glucose response. A prior evening meal will be standardised (Lite and Easy) and provided to the participants. Following baseline assessments, participants will be randomly assigned into their respective intervention groups (POSTam and POSTpm). Randomisation and allocation will be performed on unique study I.D.’s by an independent investigator using randomly permutated blocks (each block n = 4-6; http://www.randomisation.com) with males and females counterbalanced (separate allocation sequences generated) across groups. This list will then be forwarded back to the study researcher. Participants from both intervention groups will undertake three supervised 55-65 min exercise-training sessions per week (165-190min supervised per week) for a total of 12-weeks. The exercise training sessions will be performed by the participants under the supervision of a trained exercise physiologist. The testing battery for the baseline (pre-) and post-intervention assessments will be identical. A mid-intervention assessment during Week 6, will include 1,5-AG, fasting glucose and VO2 peak test only. The 1,5-AG will enable short-term (~2 week) changes in glycaemic control to be assessed. The supervised exercise intervention will consist of a progressive resistance (2-3 sets x 10/12 repetitions; 4 exercises (i.e. bench press, military press, lat-pulldown and leg press) performed in a circuit style) and brisk walking (at ~60% of VO2 peak for 35-45min). The intensity and volume of both the aerobic and resistance exercises are prescribed in accordance to the American Heart Association scientific statement. The exact exercises and repetitions performed for the resistance exercises will be determined by the supervising exercise physiologist at every training session depending on the participant's fitness levels. Additionally, for the resistance exercises, once the participants are able to complete 12 repetitions for each set of exercises on 2 consecutive sessions (2-by-2 rule), the prescribed intensity of each exercise will increase. This process will be overseen by the exercise physiologist during the training sessions. The POSTam will be performed in the morning (0530-0930h) i.e. post-breakfast) while POSTpm will be performed 30-120min after the final meal in the evening (evening meal considered >633 calories; based of an average total daily (3 meals) intake of 2000 calories). Participants in the POSTpm group will be consistently asked whether they have adhered to the diet program (i.e. no consumption of food after each exercise training session). This will be completed via over the phone reminders and a questionnaire that will be completed after each training session. As for the POSTam group, they will be asked to consume a breakfast meal at least 30 minutes prior to the start each training session for duration of the intervention. The design of the exercise intervention is such that it requires minimal equipment and can be conducted at the participant’s home following a similar model to that successfully completed previously (NCT01283854). The training workload (volume and intensity) will be monitored closely by the exercise physiologist at every session. All exercise sessions will be recorded in a logbook with attendance taken as well as sessional RPE for each individual training session over the 12-week period. Additional Physical activity advise will be focussed on increasing physical activity levels to >220min per week (i.e., additional 30 to 50 min per week), with the focus being to conduct that physical activity at the same time-period as their supervised session (but not a requirement). Dietary advise will be individualised and based on diet preference and diet history so as to align with Australian Diabetes recommendations (energy-intake; macronutrient profile only). Blood analysis: A total of 11 blood samples [baseline blood sample (6ml); and 10 venous blood samples (3ml)] will be collected via the antecubital vein during the study days for the analysis of metabolites (glucose, lactate, lipids and haematocrit). The blood samples will be transferred into EDTA-coated tubes pre-treated with 30 micro-litres of dipeptidyl peptidase IV inhibitor and aprotinin (Millipore) for later determination of metabolites via the COBAS 6000 chemistry analyzer. Our group has previously published using these techniques and all facilities are available. Baseline samples from each study day will also be assessed for HbA1c and 1,5-AG (Western Diagnostics Laboratories).