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Randomized Controlled Trial
. 2024 Nov 18;109(12):3126-3136.
doi: 10.1210/clinem/dgae344.

Loading Enhances Glucose Uptake in Muscles, Bones, and Bone Marrow of Lower Extremities in Humans

Jakob Bellman  1 , Tanja Sjöros  2   3 , Daniel Hägg  1 , Erika Atencio Herre  2   3 , Janina Hieta  4 , Olli Eskola  2 , Kirsi Laitinen  4 , Pirjo Nuutila  2   3   5 , John-Olov Jansson  1 , Per-Anders Jansson  6   7 , Kari Kalliokoski  2   3 , Anne Roivainen  2   3   8 , Claes Ohlsson  9   10
Affiliations
Randomized Controlled Trial

Loading Enhances Glucose Uptake in Muscles, Bones, and Bone Marrow of Lower Extremities in Humans

Jakob Bellman et al. J Clin Endocrinol Metab. .

Abstract

Context: Increased standing time has been associated with improved health, but the underlying mechanism is unclear.

Objectives: We herein investigate if increased weight loading increases energy demand and thereby glucose uptake (GU) locally in bone and/or muscle in the lower extremities.

Methods: In this single-center clinical trial with a randomized crossover design (ClinicalTrials.gov ID, NCT05443620), we enrolled 10 men with body mass index between 30 and 35 kg/m2. Participants were treated with both high load (standing with weight vest weighing 11% of body weight) and no load (sitting) on the lower extremities. GU was measured using whole-body quantitative positron emission tomography/computed tomography imaging. The primary endpoint was the change in GU ratio between loaded bones (ie, femur and tibia) and nonloaded bones (ie, humerus).

Results: High load increased the GU ratio between lower and upper extremities in cortical diaphyseal bone (eg, femur/humerus ratio increased by 19%, P = .029), muscles (eg, m. quadriceps femoris/m. triceps brachii ratio increased by 28%, P = .014), and certain bone marrow regions (femur/humerus diaphyseal bone marrow region ratio increased by 17%, P = .041). Unexpectedly, we observed the highest GU in the bone marrow region of vertebral bodies, but its GU was not affected by high load.

Conclusion: Increased weight-bearing loading enhances GU in muscles, cortical bone, and bone marrow of the exposed lower extremities. This could be interpreted as increased local energy demand in bone and muscle caused by increased loading. The physiological importance of the increased local GU by static loading remains to be determined.

Keywords: PET/CT; energy metabolism; obesity; positron emission tomography; weight-bearing loading; whole-body imaging.

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Figures

Figure 1.
Figure 1.
CONSORT diagram describing enrollment and study flow. The participants with screening failure did not meet all inclusion criteria and/or did meet at least 1 of the exclusion criteria as described in Methods.
Figure 2.
Figure 2.
Schematic diagram of experimental protocol. After 3 hours of intervention, each visit ended with a whole-body PET/CT scan. Three hours before each study visit, participants consumed a standardized breakfast. During the intervention, there were 4 short movement breaks (orange box and arrows). Blood samples were collected at several timepoints from −30 minutes to 180 minutes according to the description in Methods (red box and arrows). At 120 minutes, 18F-FDG was injected followed by radioactivity blood sampling from 120 to 180 minutes and finally a whole-body PET/CT at 180 minutes (blue boxes, arrows, and bracket). Created with publication rights from BioRender.com. Abbreviations: 18F-FDG, 2-deoxy-2-[18F]-fluoro-D-glucose; PET/CT, positron emission tomography/computed tomography.
Figure 3.
Figure 3.
Images from a participant's (A) right lower extremity and (B) lumbar vertebrae L3. (A) Shows a transversal plane PET/CT section with ROI drawing on (A1) quadriceps muscle, (A2) subcutaneous adipose tissue in femoral region, (A3) femoral diaphyseal bone marrow cavity, and (A4) cortical femoral bone. (B) Shows a transversal plane PET/CT section with ROI drawn on the vertebral body (B1) on the L3 vertebrae. Abbreviations: PET/CT, positron emission tomography/computed tomography; ROI, region of interest.
Figure 4.
Figure 4.
The effects of increased loading on the GU ratios between loaded extremities and not loaded extremities. (A) Cortical bone for femur/humerus GU ratio and tibia/humerus GU ratio. (B) Diaphyseal bone marrow region for femur/humerus GU ratio and tibia/humerus GU ratio. (C) Muscle for quadriceps/triceps brachii muscle GU ratio and triceps surae/triceps brachii muscle GU ratio. (D) SAT for femoral region SAT/humeral region SAT GU ratio and tibial region SAT/humeral region SAT GU ratio. Within group P-values (high load vs no load) are calculated using paired samples t-test. Data are expressed as mean ± SEM in percent of no load. *P < .05. Abbreviations: GU, glucose uptake; SAT, subcutaneous adipose tissue.
Figure 5.
Figure 5.
Effect of increased loading on plasma levels of metabolic markers. Increased loading significantly increases (A) glucose levels at 90 and 120 minutes, (B) insulin levels at 60 minutes, and (D) lactate levels at 180 minutes. No significant difference between no load and high load for free fatty acids (C). Black arrows at 120 minutes represent timepoint of 18F-FDG injection. Data are expressed as mean ± SEM. *P < .05, **P < .01. Abbreviations: 18F-FDG, 2-deoxy-2-[18F]-fluoro-D-glucose.
Figure 6.
Figure 6.
Effect of increased loading on vital parameters. No significant difference between no load and high load for systolic blood pressure (A). Increased loading significantly increases (B) diastolic blood pressure and (C) pulse at 90 and 120 minutes. Data are expressed as mean ± SEM. **P < .01, ***P < .001.
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