Effect of testosterone on insulin sensitivity, oxidative metabolism and body composition in aging men with type 2 diabetes on metformin monotherapy.

AIMS: To evaluate the effect of testosterone replacement therapy (TRT) on body composition, insulin sensitivity, oxidative metabolism and glycaemic control in aging men with lowered bioavailable testosterone (BioT) levels and type 2 diabetes mellitus (T2D) controlled on metformin monotherapy. MATERIALS AND METHODS: We conducted a randomized, double-blind, placebo-controlled study in 39 men aged 50-70 years with BioT levels <7.3 nmol/L and T2D treated with metformin monotherapy. Patients were randomized to testosterone gel (TRT, n = 20) or placebo (n = 19) for 24 weeks. Lean body mass (LBM), total and regional fat mass were measured using whole-body dual-energy X-ray absorptiometry scans. Whole-body peripheral insulin sensitivity, endogenous glucose production (EGP) and substrate oxidation were assessed by euglycaemic-hyperinsulinaemic clamp with glucose tracer and combined with indirect calorimetry. Coefficients (ß) represent the placebo-controlled mean effect of intervention. RESULTS: LBM (ß = 1.9 kg, p = 0.001) increased after TRT, while total fat mass (ß = -1.3 kg, p = 0.009), fat mass trunk (ß = -0.7 kg, p = 0.043), fat mass legs (ß = -0.7 kg, p = 0.025), fat mass arms (ß = -0.3 kg, p = 0.001), and HDL cholesterol (ß = -0.11 mmol/L, p = 0.009) decreased after TRT compared with placebo. Insulin-stimulated glucose disposal rates did not change in response to TRT compared with placebo (p = 0.18). Moreover, glycated haemoglobin, and basal and insulin-stimulated rates of EGP, lipid- and glucose-oxidation were unaltered after TRT. CONCLUSION: TRT in aging men with lowered BioT levels and T2D controlled on metformin monotherapy improved body composition; however, glycaemic control, peripheral insulin sensitivity, EGP and substrate metabolism were unchanged.

Voluntary muscle activation improves with power training and is associated with changes in gait speed in mobility-limited older adults - A randomized controlled trial.

Incomplete voluntary muscle activation may contribute to impaired muscle mechanical function and physical function in older adults. Exercise interventions have been shown to increase voluntary muscle activation, although the evidence is sparse for mobility-limited older adults, particularly in association with physical function. This study examined the effects of 12weeks of power training on outcomes of voluntary muscle activation and gait speed in mobility-limited older adults from the Healthy Ageing Network of Competence (HANC) study. We included 37 older men and women with a usual gait speed of <0.9m/s in the per-protocol analysis: n=16 in the training group (TG: 12weeks of progressive high-load power training, 2 sessions per week; age: 82.3±1.3years, 56% women) and n=21 in the control group (CG: no interventions; age: 81.6±1.1years, 67% women). Knee extensor muscle thickness (ultrasonography), strength (isokinetic dynamometry), voluntary activation (interpolated twitch technique), and gait speed (2-min maximal walking test) were assessed at baseline and post-intervention. At baseline, TG and CG were comparable for all measures. Post-intervention, significant between-group changes (TG vs. CG; p<0.05) were observed for voluntary muscle activation (+6.2%), muscle strength (+13.4Nm), and gait speed (+0.12m/s), whereas the between-group change in muscle thickness was non-significant (+0.08cm). Improvements in voluntary muscle activation were associated with improvements in gait speed in TG (r=0.67, p<0.05). Importantly, voluntary muscle activation is improved in mobility-limited older adults following 12-weeks of progressive power training, and is associated with improved maximal gait speed. Incomplete voluntary muscle activation should be considered one of the key mechanisms influencing muscle mechanical function and gait speed in older adults.