Novel Insight Regarding the Trajectory and Time‐course of Immobilisation Induced Impairment of Limb Glucose Uptake in Healthy Volunteers

Immobilisation impairs muscle glucose uptake, which is local to the affected limb. The trajectory and time‐course of this effect in man is unknown, but is central to understanding the mechanistic basis of immobilisation induced insulin resistance and therefore was the focus of this study. Ten healthy, young men (age 24.8±1.9 yr, body mass 72.0±8.2kg, body mass index 23.6±2.6kg/m 2 ) completed an oral glucose tolerance test (OGTT, 75g dextrose) before (0) and at 24, 48 and 72 hr after immobilisation of the non‐dominant arm (IMM) in a cast and having subjects wear an arm support sling. On each visit, brachial artery blood flow (BAF) was measured throughout the OGTT using Doppler ultrasound and forearm glucose uptake (FGU), calculated as a function of BAF and the difference in forearm arterialised venous to venous blood glucose concentration (AV‐V), was determined at baseline and at 10 min intervals for the initial 120 min following glucose ingestion and every 15 min for 60 min thereafter. Arterialised‐venous serum insulin concentration was determined at baseline and at 20 min intervals after glucose ingestion for 120 min and every 30 min thereafter. The same measurements were also made in the non‐immobilised arm (NIMM) at 0 and 72 hr thereby establishing a control intervention. Area under the curve (AUC) for the total 180 min was calculated for FGU, BAF and serum insulin, and time (immobilised limb) and treatment (0 and 72 hr both limbs) effects were determined using repeated measures one‐way ANOVA with Tukey post‐hoc and two‐way ANOVA with Sidak post hoc analysis, respectively. Values represent mean ± SEM and statistical significance was set at p<0.05. The University of Nottingham Medical School Ethics Committee approved the study. Forearm glucose uptake was not different between limbs at baseline (9.5±2.2 and 8.7±1.8 mmol.180min −1 in NIM and IMM, respectively), and was not reduced from baseline at 72 hr in the NIM limb (12.7±3.0 mmol.180min −1 ). However, FGU was less than at baseline in the IMM limb at 24 hr (38%; 5.4±1.1 mmol.180min −1 , p<0.05), 48 hr (67%; 3.8±0.5 mmol.180min −1 , p=0.01) and 72 hr (46%; 4.7±0.7 mmol.180min −1 , p=0.06), and was also less than in NIM at 72 hr (p<0.01). Brachial artery blood flow and arterialised‐venous serum insulin responses during the OGTT were generally unaffected by immobilisation and no different between limbs (data not shown). This study confirms the inhibitory effect of immobilisation on glucose uptake is local to the affected limb. The novel insight generated is that this effect is marked, rapid (38% within 24 hr) and sustained, and appears to be overtly muscle centric. The mechanistic basis of this precipitous induction of insulin resistance and its significance to inactivity induced impairment of metabolic health warrant further investigation. Support or Funding Information Arthritis Research United Kingdom