Insulin resistance: A key player in the onset of diverse disease pathologies

Abstract

Insulin is an endocrine peptide hormone involved in various physiological processes such as glucose uptake, lipid metabolism, cell growth and repair. Insulin resistance (IR) contributes to different biochemical abnormalities including inflammation, obesity, and prediabetes. IR is a condition associated with impairments in insulin signaling pathways, often driven by genetic predisposition, obesity, sedentary life style, lipotoxicity, oxidative stress, and chronic inflammation. Initially known as a contributor for type 2 diabetes mellitus (T2DM), IR is now understood as a central pathophysiological mechanism linking various diseases. This review highlights the multifactorial causes of IR and its contribution to disorders such as polycystic ovary syndrome (PCOS), non-alcoholic fatty liver disease (NAFLD), cardiovascular disease (CVD), chronic kidney disease (CKD), neurodegenerative disorders including Alzheimer’s disease (AD), and various cancers. This review further associates IR with conditions like obstructive sleep apnea, dermatological manifestations, circadian rhythm disruption, and susceptibility to infections such as COVID-19 adding novelty to the field. By acting as a “metabolic hub,” IR not only accelerates metabolic dysfunction but also amplifies disease progression across organ systems. Understanding these mechanisms provides new perspectives for therapeutic targeting. Future interventions may include multi-modal approaches combining pharmacological insulin sensitizers with lifestyle, circadian, and anti-inflammatory strategies. Such comprehensive approaches may reduce the burden of IR-associated disorders and improve clinical outcomes.