The effect of 10 weeks of peri-training whey protein supplementation on systemic, metabolic, and skeletal muscle molecular responses in Type-2 diabetes : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy (Sport and Exercise Science), Massey University, Wellington, New Zealand
Introduction: Type-2 diabetes (T2D) is a modern global epidemic associated with multiple health complications and economic burden. Exercise improves glycaemic control in populations with T2D with greater insulin sensitivity, muscle hypertrophy, and reduced emotional distress as possible mediators. Milk protein supplementation has been shown to produce similar benefits, raising the potential of an adjunct therapy. Therefore, the primary purpose of the thesis was to determine if whey-protein supplementation can promote skeletal muscle plasticity associated with improved glycaemic control in exercising men with T2D. Secondary aims were to determine if improvements in functional capacity and glycaemic control led to better mood and quality of life.
Methods: In a randomized, double blind clinical trial, 24 non-insulin dependent middle-aged men with T2D were allocated to a pre- and post-training whey-carbohydrate (20 grams-10 grams) supplement or isocaloric carbohydrate-only control. Participants completed 45 high-intensity endurance and resistance exercise sessions over 10 weeks. Insulin sensitivity was determined from glucose disposal rates (GDR) during a euglycaemic insulin clamp, with fasting blood glucose concentration (FBG) and the homeostatic model of assessment of insulin resistance (HOMA-IR) providing secondary measures of glycaemic control. Insulin-mediated haemodynamics; microvascular blood flow (mBF) and microvascular blood volume (mBV) were assessed at the vastus lateralis (VL) muscle via near-infrared spectroscopy. VL muscle biopsies were used to determine capillarity, intramyofibrillar mitochondrial and lipid density, citrate synthase (CS) and cytochrome c oxidase (COX) activity, and mRNA content of angiogenic and mitochondrial markers: eNOS, VEGFA, VEGFR2, PGC1-α, CS, NRF1. Aerobic capacity (VO2peak), strength (1-repetition maximum), VL muscle and subcutaneous adipose thickness, and survey-rated mood and quality of life (DASS42; SF-36) were also assessed.
Results: There were substantial increases in GDR (27.5%; 90%CI 1.2%, 60.7% and 24.8%; -5.4%, 64.8%), capillarisation (24.5%; -0.1%, 55.0 and 26.3%; 1.9%, 56.6%), and mitochondrial density (24.3%; 13.8%, 35.8% and 26.7%; 16.8%, 37.5%) in the control and whey groups respectively, with no group differences. Lipid density, COX enzyme activity, VL muscle thickness, VO2peak, 1RM strength, mood, and quality of life were also substantially increased with no group differences. Exercise training had no effect on microvascular haemodynamics; however, whey supplementation produced likely and possible improvements in mBV (16.8%; -4.3%, 42.6%) and mBF (5.9%; -3.7%, 16.3%) respectively at rest and likely improvements in both mBV (17.5%; -3.7%, 43.5%) and mBF (10.2%; 0.3%, 21.1%) under insulin-stimulated conditions. Regression analysis of the pooled 10-week change outcomes showed a positive relationship between the change in lipid density and the change in GDR (r = 0.29); negative associations between basal mBV and FBG (r=.27) and HOMA-IR (r=.30); a negative association between basal mBF and HOMA-IR (r=.48); and a positive association (r = 0.39) between the total DASS score and the change in FBG.
Conclusion: Peri-training whey protein supplementation elevated microvascular blood kinetics in middle-aged men with T2D; but did not accentuate the substantial improvements produced by the intense mixed-mode exercise training on tissue and cellular remodelling, insulin sensitivity, glycaemia, exercise capacity, mood or quality of life. The findings support the use of adjunct whey protein supplementation for elevating microvascular blood kinetics in populations with T2D, an outcome that could potentially improve the treatment of vascular diseases where microcirculation contributes to disease pathology and therefore warrants further exploration. The observation that myocellular lipid density was increased by intense exercise training and not detrimental to insulin sensitivity supports recent evidence that lipid accrual may be a favourable adaptation to exercise in populations with T2D.