A new study by the University Hospital of Tübingen, the Institute for Diabetes Research and Metabolic Diseases at Helmholtz Munich and the German Center for Diabetes Research (DZD ) shows for the first time how differently the skeletal muscles of men and women process glucose and fats. These findings could explain why metabolic diseases such as type 2 diabetes occur differently in the two sexes and why they respond differently to exercise.

Skeletal muscles are crucial for glucose metabolism, as they are responsible for around 85 percent of insulin-dependent glucose uptake. In insulin resistance, a preliminary stage of type 2 diabetes, the muscles’ ability to absorb glucose from the blood decreases. Regular exercise can improve this, but how the muscles of men and women react to this has hardly been researched to date.

The study examined muscle biopsies from 25 overweight but healthy adults (16 women, 9 men) aged around 30 years who had previously hardly done any sport. Over eight weeks, they completed endurance training three times a week with 30 minutes of cycling and 30 minutes of walking. Muscle samples were analyzed before training, after the first session and at the end of the program. Modern molecular biological methods such as epigenome, transcriptome and proteome analyses were used to investigate gender-specific differences.

The results show that men exhibit a stronger molecular stress response in their muscles after the first training session, as indicated by activated stress genes and increased myoglobin in the blood. Their muscles contain more fast-twitch fibers, which are suitable for intensive, short bursts of exercise and prefer to use glucose. Women, on the other hand, have more proteins for the absorption and storage of fatty acids, which indicates a more efficient utilization of fat. After eight weeks of training, the muscles of both sexes adapted: The differences in muscle fibers decreased, and both produced more proteins that promote the utilization of glucose and fat in the mitochondria.

These adaptations improve metabolic performance and can reduce the risk of type 2 diabetes. The findings could help to assess individual diabetes risk more precisely and tailor exercise therapies specifically to men and women. The researchers are therefore planning to further investigate the role of sex hormones such as oestrogen and testosterone and their influence on metabolic diseases in old age.

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