抵抗！ 2型糖尿病患者のインスリン感受性改善のための血流制限抵抗トレーニング (RESIST)

Type 2 diabetes (T2D) is characterized by an increasing insensitivity of muscle, fat and liver cells to the hormone insulin. About 9% of the global population is affected by this condition and mortality risk is twice as high in individuals with diabetes compared to similar-aged people without diabetes.

Muscle is of particular importance for glucose homeostasis, since in healthy people it accounts for 80-90% of postprandial insulin-stimulated glucose disposal. After cellular uptake of glucose by the specialized glucose transporter 4 (GLUT4), glucose is phosphorylated and stored as glycogen. In individuals with obesity or T2D, the capacity for insulin to facilitate glucose uptake and glycogen synthesis is impaired. This reduced response of a given insulin concentration to exert its biological effect is termed insulin resistance. Subsequent diminished insulin secretion due to β-cell failure results in fasting hyperglycemia and overt diabetes. Importantly, muscle insulin resistance is the initial defect occurring in the development of T2D and precedes the clinical development of the disease by up to 20 years.

Thus, the preservation of skeletal muscle function is essential for people with T2D who have an increased risk of sarcopenia. On the one hand high intensity resistance training (HIT) with 80 % one-repetition maximum (%1-RM) is a well-recognized strategy to improve muscle strength and glycemic control for individuals with T2D, on the other hand elderly or obese people may not be able to tolerate these high loads. Blood flow restriction training (BFRT) with low loads (20-30% 1-RM) has consistently demonstrated comparable effects to HIT and seems to be a promising alternative to increase muscle function.

During the BFRT the muscle becomes hypoxic due to a brief occlusion of venous blood flow using a tourniquet while exercising. Consequently metabolites like lactate, growth hormone (GH) and insulin like growth factor (IGF-1) are released and result in muscle hypertrophy through activating the collagen synthesis and the recruitment of satellite cells. Furthermore cell swelling based on venous blood pooling, reactive hyperemia and metabolite accumulation has been shown to increase protein synthesis by activating the mammalian Target of Rapamycin Complex 1 (mTORC1) pathway. Also, BFRT increases the level of reactive oxygen species (ROS) which may lead to higher glucose uptake during exercise. Last but not least higher threshold motor units (fast twitch fibers) are recruited due to hypoxia and metabolite accumulation.

Although there is a significant inverse relationship between muscle strength and the risk of cardiovascular mortality, cardiovascular adaptations to resistance training are under-explored and poorly understood.

The study therefore aims to investigate the metabolic and cardiovascular effects of BFRT with low loads in individuals with T2D.