The effect of exercise timing on blood glucose control in individuals with Type 2 diabetes mellitus

Study Design: Potential participants will 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. Thereafter, participants from both the T2DM group and Control Group (Healthy but overweight individuals with no T2DM) will be randomly allocated into one of the two intervention training groups (pmEX and amEX) to begin their 12-week exercise training intervention. Mid-intervention assessments will occur during Week 6 to assess: (i) glycemic 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 (DEXA, height, weight, waist circumference), aerobic fitness assessment (VO2 peak test; modified Bruce treadmill test protocol), diet history, appetite questionnaires, 14-day sleep and physical activity monitoring (Actigraph and diar), 24 h skin temperature (ibutton, data logger), and validated mood chart. Additionally, participants will attend the laboratory (study day) for assessment of PPG and glucose-regulatory hormonal responses as well as assessment of autonomic function. The study day will involve assessment of two distinct postprandial responses (mixed-meal tolerance tests) comprising the first and second meal of the day (second meal phenomenon; the glucose response to the second meal should be less than the first meal). Measures of glycaemic control (HbA1c; 1,5-anhydroglucitol [1,5-AG]) will be collected from the baseline sample into separate EDTA tubes. Following the baseline assessments, participants will be randomly assigned into their respective intervention groups (amEX and pmEX) for both the T2DM and Healthy Control groups. Randomisation and allocation will be performed on unique study I.D.'s by an independent investigator using randomly permutated blocks (http://www.randomisation.com) with males and females counterbalanced across groups. This list will be 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 (165-190 min supervised per week) for a total of 12 weeks. The exercise training sessions will be performed in groups of 3-5 individuals at Murdoch University Strength and Conditioning gym under the supervision of a trained exercise physiologist. The testing battery for the baseline (pre-) and post-intervention assessments will be identical. The mid-intervention assessment will include 1,5-AG, fasting glucose and VO2 peak test only . The supervised exercise intervention will consist of a progressive resistance (2-3 sets x 10/12 repetitions; 4 exercises targeting upper- and lower-body performed in a circuit style) and brisk walking (at 65% VO2 peak for 35-45 min). 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 exercise sessions (2-by-2 rule), the prescribed intensity of each execise will increase. This process will be overseen by the exercise physiologist during the training sessions. The amEX (0500-1000) will be performed 30-120 min after "breakfast" (food consumption of >200 Cal), while the evening exercise will be performed 30-120 min after the last meal of the day. Participants in the pmEX group will be asked to refrain from consuming food after the evening exercise session. 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. An interviewer-administered 24 h recall will be captured on five separate occasions beyond the diet history assessment to assess diet-related changes (which may be added to the model as a covariate). Blood analysis: A total of 15 blood samples (3ml) will be collected during the study-days. A portion of whole blood (200 micro-litres) will be analysed immediately using a clinical benchtop analyser (GEM3500) for metabolites (glucose, lactate, haematocrit). The remaining blood 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 plasma hormone concentrations of insulin, C-peptide, glucagon, GLP-1, and gastric inhibitory polypeptide (GIP) using a MILLIPLEX magnetic bead–based quantitative multiplex immunoassay with the MAGPIX instrumentation (Millipore). 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 (Clinipath Laboratories) and 1,5-AG (Glycomark).