Can protein improve glucose tolerance in older adults with type-2 diabetes??

INTERVENTION: Participants will be randomly allocated to 1 of 3 dietary supplementation groups: 1) wool derived protein, 2) whey protein, or 3) placebo. The study duration will be 17 weeks, which includes an initial two testing weeks, 14 weeks of exercise and protein supplementation co‐intervention and a final testing week.. For the 2 week familiarisation, all participants will consume the placebo. The supplement will only be consumed during weekdays, to coincide with the exercise sessions. Supplement: will be delivered in the form of health bars and capsules, to be consumed 2 times per day (post‐exercise, 1 hour prior to bedtime), separated by at least 3 hours. The total daily protein dose in each treatment arm will be 40 gram: a) 17 g KDP+23 g whey, b) 40 g whey, or c) placebo ‐ no added protein. The placebo bars will have the supplemental protein energy content replaced with gluten free flour and refined carbohydrate (maltodextrin, glucose) and fat to match energy and minimize protein content. Exercise: Exercise Physiologists will supervise 5 days/week intermittent high‐intensity mixed‐mode, group‐based exercise program designed to achieve a fixed‐rate 2% gain in exercise load/week. Each training session will be approximately 60 minutes in duration, including: a. Warm‐up:10 min light cardio machine exercise and stretching b. Days 1, 2, 4, 5: aerobic (stationary cycle) exercise, comprising a mix of continuous exercise and anaerobic intervals (70‐90% of peak power and recovery at 40‐50% of peak power). Exercise intensity will be standardised by having all sessions conducted on calibrated ergometers c. Day 3: standardised circuit resistance training (10‐30% of the exercise 1 repetition maximum) emphasising the legs d. Cool‐down: 5‐10 minutes of stretching to cool down Subjects will be required to attend a minimum of 60 sessions over the 14 weeks, and will be provided with the opportunity to complete any missed sessions on weekends. To ensure adherence to exercise the participants will be supervised. The participants will be required to complete a 3‐day dietary recall each time they visit the laboratory for testing, and a text message will be sent to remind the participant to consume the evening dose. CONDITION: Non‐insulin dependent type‐2 diabetes PRIMARY OUTCOME: Whole‐body glucose disposal rate during hyperinsulinemic euglycaemic clamp SECONDARY OUTCOME: Blood cholesterol, triglycerides, fasting glucose/insulin, Hb1Ac, alkaline phosphatase, total protein Body composition, using anthropometry and bio‐impedance analysis Carotid arterial stiffness. Measured using B‐mode ultrasound Daily physical activity, assessed over 7 day using accelerometry Functional health and well‐being via psychometric assessment using ; SF36 and DASS GLUT4 density and sarcolemmal translocation using differential centrifugation and immunoblot or ELISA, immunoflurochemistry. Skeletal muscle tissue harvested will be from the vastus lateralis. INCLUSION CRITERIA: Thirty‐six men and women with non‐insulin dependent Type‐2 diabetics (diagnosed for a minimum of 1 year), aged 35‐70, BMI 25‐40, HbA1c >48 mmol/mol, stable weight and not having participated in regular exercise in the past 6 months ; Insulin‐stimulated skeletal muscle (vastus lateralis) mircovascular blood flow, assessed using near‐infrared spectroscopy during the hyperinsulinemic euglycaemic clamp Metabolomics (urine) Mitochondrial capacity of the vastus lateralis muscle, assessed using near‐infrared spectroscopy Mitochondrial metabolic function will be gauged via citrate synthase and cytochrome oxidase IV activity using ELISA. Skeletal muscle tissue harvested will be from the vastus lateralis. Skeletal muscle capillary density by light microscopy. Skeletal muscle tissue harvested will be from the vastus lateralis. Sleep behaviour, assessed over 7 day using accelerometry Tissue fibrosis plasticity by endomyosium/myofibril area using light microscopy. Skeletal muscle tissue harvested will be from the vastus lateralis. anti‐oxidant biology (e.g. glutathione, glutathione peroxidase pathways) using biochemical methods. Skeletal muscle tissue harvested will be from the vastus lateralis. contraction‐mediated skeletal muscle (vastus lateralis) microvascular blood flow, assessed using near‐infrared spectroscopy during leg‐kicking exercise dynamic leg strength. Tested as 1RM on a leg press gene and protein expression using RT‐PCR, transcriptome, proteome and associated molecular methods. Skeletal muscle tissue harvested will be from the vastus lateralis. isokinetic leg strength on a Biodex dynamometer isometric leg strength on a Biodex dynamometer maximal oxygen uptake via indirect calorimetry using an incremental cycle test to exhaustion phosphorylation status of insulin signalling pathway (PI3K, AS160 on multiple phosphorylation sites) using immunoblot and immunoflurochemistry. Skeletal muscle tissue harvested will be from the vastus lateralis.