Dietary bioactive compounds targeting insulin resistance: mechanisms and preventive potential

Insulin resistance (IR) is a condition in which the biochemical response to insulin is impaired due to both genetic and environmental factors. Insulin is a peptide hormone released by pancreatic β-cells that plays a systemic role in the regulation of glucose homeostasis. Under insulin-resistant conditions, higher concentrations of insulin are required to achieve the same downstream effects, leading to hyperinsulinemia and impaired glucose tolerance. IR is associated with several metabolic abnormalities, including obesity, dyslipidemia, impaired glucose tolerance, and type 2 diabetes, and represents a key early event in the development of this disease. Moreover, IR has a very high global prevalence, which underlies the breadth of its clinical implications and the associated health impact. Targeting insulin resistance represents an important strategy not only for therapy but also for prevention. In this context, nutritional strategies and functional foods rich in bioactive compounds have emerged as promising approaches to improve insulin sensitivity. Dietary patterns characterized by a high intake of whole grains, fruits, vegetables, legumes, and unsaturated fatty acids have been associated with improved metabolic control and a reduced risk of insulin resistance. Moreover, increasing evidence suggests that specific dietary bioactive compounds, such as polyphenols, flavonoids, dietary fibers, omega-3 fatty acids, and other plant-derived metabolites, may exert beneficial metabolic effects by modulating key mechanisms involved in IR, including oxidative stress, chronic low-grade inflammation, gut microbiota composition, and cellular signaling pathways regulating glucose and lipid metabolism. In this review, we evaluate emerging nutritional strategies and bioactive compounds involved in the prevention and management of IR, which consequently have significant implications at the public health level in terms of risk prevention and improved prognosis.