Obesity, Insulin Resistance and Type 2 Diabetes Mellitus - Pathophysiological Mechanisms and Exercise-Based Strategies

Abstract

Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder characterized by chronic hyperglycemia resulting from insulin resistance and progressive pancreatic β-cell dysfunction. Its pathogenesis involves multiple interconnected mechanisms affecting skeletal muscle, liver, adipose tissue, and systemic metabolic regulation. Obesity, particularly visceral adiposity, plays a central role in the development of insulin resistance through lipotoxicity, mitochondrial dysfunction, endoplasmic reticulum stress, and chronic low-grade inflammation. These mechanisms disrupt insulin signaling and contribute to progressive metabolic dysfunction. Physical activity represents one of the most effective non-pharmacological interventions in both prevention and treatment of T2DM. Regular exercise improves glucose uptake in skeletal muscle, enhances insulin sensitivity, reduces visceral adipose tissue, and improves overall metabolic flexibility. Current recommendations emphasize at least 150 minutes of moderate-intensity aerobic exercise per week combined with resistance training performed 2–3 times weekly. This narrative review summarizes current knowledge regarding the molecular basis of insulin resistance and highlights the therapeutic role of physical activity as a key strategy in the management of T2DM.