Intense exercise decreases the cerebral metabolic ratio of O 2 to carbohydrates (glucose + 1 / 2 lactate) and the cerebral lactate uptake depends on its arterial concentration, but whether these variables are influenced by O 2 availability is not known. In six males, maximal ergometer rowing increased the arterial lactate to 21.4 ± 0.8 mM (mean ± S.E.M.) and arterial-jugular venous (a-v) difference from −0.03 ± 0.01 mM at rest to 2.52 ± 0.03 mM (P < 0.05). Arterial glucose was raised to 8.5 ± 0.5 mM and its a-v difference increased from 1.03 ± 0.01 to 1.86 ± 0.02 mM (P < 0.05) in the immediate recovery. During exercise, the cerebral metabolic ratio decreased from 5.67 ± 0.52 at rest to 1.70 ± 0.23 (P < 0.05) and remained low in the early recovery. Arterial haemoglobin O 2 saturation was 92.5 ± 0.2% during exercise with room air, and it reached 87.6 ± 1.0% and 98.9 ± 0.2% during exercise with an inspired O 2 fraction of 0.17 and 0.30, respectively. Whilst the increase in a-v lactate difference was attenuated by manipulation of cerebral O 2 availability, the cerebral metabolic ratio was not affected significantly. During maximal rowing, the cerebral metabolic ratio reaches the lowest value with no effect by a moderate change in the arterial O 2 content. These findings suggest that intense whole body exercise is associated with marked imbalance in the cerebral metabolic substrate preferences independent of oxygen availability.

Background Weight loss is critical for preventing and managing obesity-related diseases. There is a notable lack of valid and reliable means to manage patients with overweight/obesity and knee osteoarthritis (KOA). Objective To determine the efficacy and safety of liraglutide in a 30 mg/d dosing in patients with overweight/obesity and KOA. Methods The trial was designed as a randomized controlled trial including patients between the age of 18 and 74 y with KOA and a BMI ≥27 (measured in kg/m2). Patients underwent a pre–random assignment diet intervention (week –8 to 0). At week 0, patients having lost &gt;5% of their body weight were randomly assigned to liraglutide 3 mg/d or placebo for 52 wk. The coprimary outcomes were changes in body weight and the Knee injury and Osteoarthritis Outcome Score (KOOS) pain subscale from week 0 to 52. Results In total, 168 patients enrolled and 156 were randomly assigned to receive liraglutide or placebo. Patients experienced a significant reduction in body weight and KOOS pain during the pre–random assignment dietary intervention period (week −8 to 0). From week 0 to 52 there was a significant difference in body weight between the liraglutide and placebo group (mean changes: −2.8 and +1.2 kg, respectively; group difference, 3.9 kg; 95% CI: −6.9, −1.0; P = 0.008). There was, however, no group difference in KOOS pain (mean changes: 0.4 and –0.6 points, respectively; group difference, 0.9 points; 95% CI: −3.9, 5.7; P = 0.71). Treatment-emergent adverse events related to the gastrointestinal system were experienced by 50.2% and 39.2% of patients in the liraglutide and placebo groups, respectively. Conclusions In patients with KOA and overweight/obesity liraglutide added after an 8-wk pre–random assignment diet induced a significant weight loss at &gt;52 wk but did not reduce knee pain compared to placebo. This trial was registered at clinicaltrials.gov as NCT02905864.

ObjectiveTo compare the efficacy of an exercise and education programme with open-label placebo given as intra-articular injections of inert saline on pain and function in individuals with knee osteoarthritis (OA).MethodsIn this open-label, randomised controlled trial, we recruited adults aged ≥50 years with symptomatic and radiographically confirmed knee OA in Denmark. Participants were randomised 1:1 to undergo an 8-week exercise and education programme or four intra-articular saline injections over 8 weeks. Primary outcome was change from baseline to week 9 in the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire pain subscale (range 0 (worst)–100 (best)). Prespecified equivalence margins of ±8 KOOS pain points were chosen for the demonstration of comparable efficacy. Key secondary outcomes were the KOOS function and quality of life subscales, and patients’ global assessment of disease impact.Results206 adults were randomly assigned: 102 to exercise and education and 104 to intra-articular saline injections. For the primary outcome, the least squares mean changes in KOOS pain were 10.0 for exercise and education and 7.3 for saline injections (difference 2.7 points, 95% CI −0.6 to 6.0; test for equivalence p=0.0008). All group differences in the key secondary outcomes respected the predefined equivalence margins. Adverse events and serious adverse events were similar in the two groups.ConclusionIn individuals with knee OA, an 8-week exercise and education programme provided efficacy for symptomatic and functional improvements equivalent to that of four open-label intra-articular saline injections over 8 weeks.Trial registration numberNCT03843931.