Paradigm Shift in the Pathophysiology and Treatment of Insulin Resistance: From Epigenetic Determinants to the Continuous Glucose Monitoring (CGM) Revolution
DOI:
https://doi.org/10.12775/JEHS.2026.90.70467Keywords
insulin resistance, hyperinsulinemia, continuous glucose monitoring, epigenetics, GLP-1 agonists, metabolic syndromeAbstract
Introduction and purpose. The classical approach to metabolic diseases traditionally positioned insulin resistance as the primary cause of evolving pathology. However, modern evidence-based medicine indicates a critical need to redefine this view, demonstrating that hyperinsulinemia is an early, independent damaging factor that may precede clinical dysglycemia by a full decade. The fundamental aim of this study is to thoroughly analyze scientific evidence regarding the multifaceted pathogenesis, novel diagnostics, and modern treatment paradigms of insulin resistance and hyperinsulinemia.
A brief description of the state of knowledge. Based on a comprehensive review of 49 targeted publications, it was shown that insulin resistance pathophysiology involves complex DNA methylation mechanisms, aldosterone excess, and consequent changes in neural connectivity. Furthermore, genetic analyses definitively confirm the causal link between hyperinsulinemia and systemic complications like gout. A highly effective diagnostic tool is the widespread adoption of Continuous Glucose Monitoring (CGM) systems, which measure interstitial fluid glucose and enable rigorous analysis of Time in Range (TIR) and Time Above Range (TAR) in individuals without diagnosed diabetes. Therapeutically, pivotal recent trials demonstrate the high efficacy of multi-receptor incretin agonists (e.g., GLP-1, GIP, Glucagon) and SGLT2 inhibitors in radically improving insulin sensitivity and comprehensive cardiometabolic profiles.
Summary. Monitoring subclinical glucose fluctuations with advanced CGM technologies is a highly useful prophylactic tool. Interventions based on targeted lifestyle modifications and modern multi-target pharmacotherapy successfully promote the regression of prediabetes, significantly reducing the risk of vascular complications. Ensuring up-to-date classifications is necessary for accurate differential diagnosis and early implementation of targeted interventions.
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Copyright (c) 2026 Emilia Piaszczyńska, Magdalena Mulawa , Dominika Matacz , Karolina Mazur, Kamila Krycia , Aleksandra Gałuszka, Karolina Różycka , Sandra Drabik, Maja Gałuszka, Adrianna Adamczyk
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