Oral Galactose as a Substrate for Post-Exercise Skeletal Muscle Glycogen Repletion in Individuals With Type 1 Diabetes

Previous studies using intravenously administered galactose have demonstrated direct uptake by human skeletal muscle, with uptake increasing following exercise. These findings challenge the traditional view that galactose must first be converted to glucose in the liver before utilization by peripheral tissues and suggest that exercise may stimulate galactose uptake through partly insulin-independent mechanisms. However, it remains unknown whether the tissue distribution and uptake kinetics of orally ingested galactose resemble those observed during intravenous administration.

The primary hypothesis is that prior exercise increases skeletal muscle galactose uptake. A secondary hypothesis is that co-ingestion of glucose reduces peripheral galactose uptake, potentially through increased hepatic extraction.

To investigate this, eight healthy participants and eight individuals with T1D will complete two study days in a randomized crossover design. On each study day, participants will perform 30 minutes of unilateral high-intensity leg exercise, with the non-exercised leg serving as an intra-individual control.

Following exercise, participants will ingest either 30 g galactose or 30 g galactose combined with 30 g glucose together with 100 MBq of ¹⁸F-FDGal. A 90-minute dynamic whole-body PET scan will be performed to characterize the tissue distribution and kinetics of ¹⁸F-FDGal, followed by a static brain scan. Tissue-specific time-activity curves will be extracted and, together with serial blood sampling, used for kinetic modeling of galactose uptake in skeletal muscle, liver, heart, and brain. Blood samples will be collected throughout the experiment to characterize systemic metabolic responses.

The unilateral exercise model enables direct within-participant comparison of galactose uptake between exercised and resting skeletal muscle, while the crossover design allows assessment of how glucose co-ingestion affects galactose distribution and uptake.

Inclusion criteria

• Healthy or T1D
• BMI 18,5-30 kg/m2
• Singed informed consent

Exclusion criteria

• Clinically significant heart, lung, kidney, liver, endocrine, or malignant disease based on information collected during the initial screening visit as well as blood tests
• Lack of awareness of hypoglycemia episodes
• Blood donation within the last 3 months
• Smoking
• Alcohol or substance abuse
• Participation in other studies involving ionizing radiation within the last 6 months
• Claustrophobia
• Inability to train one leg for one hour