Why Do Some Type 2 Diabetes Patients Fail to Respond to Exercise Therapy?

Regular physical activity is effective lowering the risk of diabetes, but some patients do not see improved insulin sensitivity.

Although physical activity on a regular basis has proven highly effective in lowering the risk of diabetes, some individuals respond differently.

In a new study, researchers found that the activation of TGF-beta may be a cause. It has been reported that approximately 1 in 5 participants in training intervention studies fail to achieve a positive physical impact of exercise (non-responders).

In a study published in Diabetes, researchers wanted to examine the mechanisms behind this effect. Researchers enrolled 20 middle-age subjects to complete an 8-week endurance training program that consisted of cycling and walking at the Sports Medicine in Tübingen.

“All participants were at high risk to develop type 2 diabetes,” said first study author Anja Böhm. “The aim was to improve their insulin sensitivity and to lower their diabetes risk. Before the training intervention, none of the participants were very physically active.”

Afterwards, researchers examined the molecular changes in the skeletal muscles. They found that the positive effect on genes important for glucose and fat burning were evident in the muscles of participants whose insulin sensitivity had improved.

However, the respective adjustments in the muscles of non-responders were reduced. When the muscles of non-responding participants were analyzed, researchers found that the messenger substance TGF-beta was activated after training.

To confirm these findings, Christoph Hoffman from the University Hospital Tübingen, subsequently conducted experiments using human skeletal muscle cells. The results of the experiments showed that TGF-beta inhibited the transcription of genes important for glucose and fat burning, and reducing insulin sensitivity.

“At the moment we are still trying to understand what causes TGF-beta to be activated in the muscle of some participants,” said lead researcher Cora Weigert. “There is some evidence that a different training program where the intensity or length of training is adapted to an individual’s ability to respond to physical exercise would be successful, and would help to prevent diabetes. I myself am convinced that everyone — given a suitable training program – can lower their personal diabetes risk.”