Can Amino Acids in Combination with Exercise Training Improve Metabolic Flexibility and Cardiovascular Health in Type-2 Diabetics?

INTERVENTION: Participants randomised to the AA + EX group will underake a 10‐week weekday morning small‐group mixed‐mode exercise program and consume a pre‐ and post‐exercise supplement. All sessions willl be supervised by exercise physiologists. The exercise program entails 3 days of 20 minutes of interval cycling on an ergometer for 20 minutes at 30% and 60% of maximal work capacity, and 2 days of 30 minutes of upper‐body resistance circuit training at 60% of 1 repitition maximum plus core exercises (plus warm up and cool down exercises). Maximal cycling work capacity and maximum strength on resistance exercises will be reassesed fortnightly and workloads adjusted to maintain prescribed intensities. The treatment is a 200ml pre‐packaged drink containing 15g whey protein, 3g leucine, 15g carbohydrate, and 5g of fat. Drinks will be consumed immediately before and after exercise and at the same time by participants in the supplement only group. CONDITION: Non‐insulin dependent type‐2 diabetes PRIMARY OUTCOME: Flow mediated dilation of the brachial artery by ultrasound Whole‐body glucose disposal rate during hyperinsulinemic euglycaemic clamp SECONDARY OUTCOME: Aerobic capacity via breath by breath gas analysis during an incremental maximal cycle ergometer test Arterial stiffness at the brachial artery by pulse wave analysis Concentration of myostatin and associated regulators (follistatin, FLRG, activin‐receptor) in skeletal muscle via immunoblot Functional health and well‐being via psychometric assessment using SF36 Genetic adaptation to support other outcomes via gene array and epigenetic analysis HOMA from fasting plasma glucose and insulin concentration Insulin stimulated GLUT4 translocation associated signaling protein activity via immunoblot of phosphorylated IRS, PI3K, AS160, and akt, in Vastus Lateralis muscle Insulin stimulated skeletal muscle capillary recruitment at the Vastus Lateralis via NIRS Intramyocellular lipid content via electron microscopy densitometry Maximal strength via 1 repetition max test on leg press and smith machine bench press Metabolic flexibility by respiratory exchange ratio during breath by breath gas analysis Microvascular blood flow at the Vastus Lateralis muscle by NIRS Mitochondrial capacity at the Vastus Lateralis muscle by near‐infrared spectroscopy (NIRS) Plasma concentration of cholesterol, triglycerides, and high‐density lipoproteins Skeletal muscle capillary density via immunocytochemistry Skeletal muscle growth via immunocytochemistry of myocellular volume and bioelectrical impedance of total lean body mass Skeletal muscle mitochondrial function 1) density via electron microscopic densitometry 2) mitochondrial enzyme activity (citrate synthase, cytochrome c oxidase and 5 subunits, beta‐hydroxyacyl‐CoA‐dehydrogenase via immunoblot Skeletal muscle tissue fibrosis via endomysium cross‐sectional area (immunocytochemistry) and hydroxyproline concentration (ELISA assay) Total and sarcolemmal glucose transporter 4 content via immunoblot Whole‐body fat mass via bioelectrical impedence INCLUSION CRITERIA: Non‐insulin dependent Type‐2 diabetics (T2DM)diagnosed for a minimum of 1 year, HbA1c between 7 and 9%, BMI 25‐32, stable weight and non‐participation in regular exercise in past 6 months.