Uncovering bone-muscle-fat interaction in patients with type 2 diabetes: effects of acute and chronic exercise

The study involves three main parts. 1) screening and baseline assessments related to bone, muscle and body composition health, 2) acute high intensity interval exercise (HIIE) and 3) chronic exercise training (10-weeks). For all acute HIIE and exercise training visits, participants will be supervised by an Exercise Physiologists in a 1:1 or 1:2 format. All the assessments and exercise training will be conducted face-to-face at Victoria University. Acute sessions at baseline will be conducted within 7 days of screening, acute sessions following 4 and 10 weeks of exercise training will be conducted after 72 hours of the last exercise training session. EFFECTS OF ACUTE EXERCISE We will examine the effects of acute high intensity interval exercise (HIIE) on markers of bone, muscle and fat metabolism as well as changes in markers of metabolic and cardiovascular (CV) risk (glucose, lipids, inflammation etc). This (identical) acute HIIE session will also be performed following 4 and 10 weeks of HIIE training, with each session taking approximately 4 hours. Should the participant decide to complete an OGTT at the end of the 1st acute session, this will take the duration to 7 hours total. Blood sampling will be taken before exercise, immediately following exercise, and up to 180 min post-exercise. Urine samples will be taken before and following exercise. Participants can elect to have none, one (at rest) or six (1 at rest and 1 following each acute exercise session) muscle and adipose tissue biopsies. Muscle will be analysed for protein degradation and protein synthesis pathways. Other novel markers associated with muscle, bone and fat health may also be assessed. Twenty-four hours prior to the acute HIIE session participants will be asked to refrain from any formal exercise, consume their normal diet and not take caffeine or alcohol. Participants will arrive to our lab between 7-8am after an overnight fast. At the start of each visit, a cannula will be inserted into the antecubital vein. At each testing visit we will take six blood samples (~20 to 25 ml each), one at rest before exercise, and one immediately following exercise, then at 30, 60, 120 and 180 mins post-exercise. The total blood volume taken in one visit is around 140ml. The acute HIIE session incudes 4 sets x 4 minutes of cycling (on a cycle ergometer) at 90-95% of heart rate reserve (HRR) with 2 minutes of active recovery between sets. Participant will be able to consume water, however, they will be unable to eat until the end of the visit. Participants will also be asked to complete some simple short questionnaires. The Feelings scale, the Depression Anxiety Stress Scale (DASS) and The subjective exercise experience scale (SEES). Participants will also have the option of completing an oral glucose tolerance test (OGTT) following the first acute session. The OGTT will be completed at baseline, following the 1st acute exercise session (optional) and post-intervention at the Victoria University Exercise Physiology Lab. A cannula will be inserted into the forearm by a qualified and experienced investigator at the beginning of the trial to collect venous blood. Catheters are used when several blood samples are needed from one site over a brief duration such as to be used here. The oral glucose tolerance test will take 2 hours in duration. During this test, participants will consume a glucose beverage (75g of glucose) and serial blood samples (4ml at each interval) will then be taken at regular intervals (every 30 mins: 0mins, 30mins, 60mins, 90mins and 120mins) to monitor blood glucose and insulin concentrations for the determination of insulin sensitivity and glucose tolerance. The total amount of blood drawn will be 20ml. Catheterisation and blood sampling is a well-established and accepted technique routinely performed at Victoria University. EFFECTS OF 4 and 10-WEEKS HIIT EXERCISE TRAINING Following the acute exercise, participants will be randomised (using 2:1 ratio of randomisation, sealed envelope) to receive either 10 weeks of exercise training, or 10 weeks of standard clinical care (control). Training will be 3 sessions per week. The format of these sessions will be the same as the acute HIIE session 4 sets x 4 minutes of cycling (on a cycle ergometer) at 90-95% of HRR with 2 minutes of active recovery between sets. Blood pressure and heart rate will be monitored before and after exercise. Both before, mid and after the chronic training period we will administer the third version of Behavioral Regulation in Exercise Questionnaire (BREQ 3) to assess baseline exercise motivation and determine if the applied intervention positively impacts internal or external motivation for exercise participation. The study coordinator will be in close contact with the participant to arrange all training sessions and will maintain a session attendance checklist to monitor adherence to the intervention. Following 4 and 10-weeks of the intervention (exercise training and control) and between 48 to 72 hours after their acute exercise visits, participants will attend Victoria University for mid intervention (4 week) and post intervention assessments (10 weeks) which will be a repeat of the baseline testing and acute exercise.