Exercise as non-pharmacological therapy for type 2 diabetes

Abstract

Type 2 diabetes is a metabolic, cardiovascular, muscular and inflammatory disease. Therefore, exercise should be considered a central therapeutic intervention rather than a simple lifestyle recommendation. During skeletal muscle contraction, glucose uptake increases through a pathway that is partly independent of insulin and involves GLUT-4 translocation, AMPK activation, calcium-dependent signaling, AS160/TBC1D4, Rab proteins, RAC1 and enhanced microvascular blood flow. The interaction between insulin and exercise helps explain how skeletal muscle takes up glucose during physical activity and how, after exercise, insulin sensitivity increases in previously active muscle to promote glycogen resynthesis. These mechanisms improve glucose and fatty acid utilization, reduce lipotoxicity and promote mitochondrial adaptations.

Skeletal muscle should also be regarded as an endocrine organ. Through myokines and exercise-induced factors, or exerkines, contracting muscle communicates with adipose tissue, liver, cardiovascular system, bone and brain. Interleukin-6 released by myocytes during exercise does not necessarily reproduce the pro-inflammatory profile of macrophage-derived IL-6. On the contrary, exercise-induced IL-6 participates in anti-inflammatory responses, stimulates IL-1 receptor antagonist and IL-10, and contributes to energy metabolism. This concept helps explain why regular exercise reduces low-grade chronic inflammation, visceral adiposity, oxidative stress and cardiometabolic risk.

Clinical evidence shows that exercise improves HbA1c, blood pressure, body composition, lipid profile, functional capacity and quality of life. Cardiorespiratory fitness is a powerful prognostic marker and should be considered a clinical vital sign. However, implementation remains a major challenge. In a multicenter Argentine study of adults with type 2 diabetes, 52.3% showed low levels of physical activity. The most frequently reported barriers were lack of willpower, lack of energy and lack of time. Low physical activity was associated with older age, higher HbA1c, higher BMI, female sex and lack of social support.

Therefore, exercise prescription should be individualized, progressive and realistic. It should include reduction of sedentary behavior, frequent interruptions of prolonged sitting, promotion of daily-life physical activity, at least 150 minutes per week of moderate-intensity aerobic exercise, and resistance training two to three times weekly. Exercise is a biological, accessible and powerful “polypill” for the prevention and treatment of type 2 diabetes.