Influence of a 12 week at-home resistance exercise program on ¹³C-glucose metabolism in patients with metabolic...

Metabolic myopathies (MM) are a diverse group of genetic disorders that impair cellular energy metabolism, resulting in exercise intolerance and fatigue. Previous studies have reported benefits of physiotherapy in patients with MM, however, objective assessments of their efficacy remain limited. The ¹³C glucose breath test (¹³C-GBT) is a non-invasive measure of glucose metabolism through the detection of ¹³CO₂ expelled from the tricarboxylic acid cycle. This study utilizes the in vivo¹³C-GBT assessment pre- and post-therapeutic intervention to evaluate the impact of a supervised 12 wk. at-home resistance training program on patients with MM.

The first experiment was to assess the repeatability of the in vivo¹³C-GBT through triplicate study days in healthy controls. The second experiment was to assess ¹³C-glucose metabolism in participants with MM pre- and post-therapeutic intervention.

Six healthy adult controls (3 F: 3 M) aged 22-29 y, and three adolescent participants (1 F: 2 M) aged 10-18 y with diagnosed MM were recruited. Participants completed up to three study days pre- and post-intervention, consuming a 1.5 mg/kg body weight dose of [U-¹³C₆] d-glucose, and 1.5 g/kg body weight Trutol® glucose beverage. Breath samples collected during the 4 h study day were analyzed for ¹³C enrichment with isotope ratio mass spectrometry, and used to calculate rate of glucose oxidation (mg/kg/min). Measured ¹³C enrichment was used to calculate the rate of glucose oxidation (mg/kg/min) and interpreted with Area Under the Curve analysis, and determination of maximum rate (C_max).

Repeatability of the ¹³C-GBT was confirmed in healthy participants, with average coefficients of variation (CV) being 8.9 % in males and 8.6 % in females at C_max. Among MM participants, exercise intervention increased glucose oxidation 23.5 % in subject MM-01 (F, 14 y), and 9 % in MM-02 (M, 16 y); but decreased -11.7 % in MM-04 (M, 17 y). All subjects showed a marginal increase in lean body mass (2-4 %).

The non-invasive 4 h ¹³C-GBT protocol shows potential as a feasible tool for clinicians to monitor glucose utilization due to its low patient burden and good repeatability. Future work should validate the repeatability of the assay in a larger patient population to confirm its translational potential to guide the management of MM patients.