Biomarkers of insulin sensitivity/resistance

In recent years, remarkable advancements in elucidating the intricate molecular underpinnings of type 2 diabetes mellitus (T2D) have been achieved. Insulin resistance (IR) has been unequivocally acknowledged as the driving pathogenetic mechanism of T2D, preceding disease onset by several years. Nonetheless, diagnostic tools for ascertaining IR are lacking in current clinical practice, representing a critical unmet need; use of the hyperinsulinemic-euglycemic glucose clamp, widely accepted as the gold standard method for evaluating IR at present, is cumbersome in a clinical setting. Thus, the development of well-validated, reliable, and affordable biomarkers of IR has attracted considerable attention from the research community. The biomarkers under investigation can be divided into two major categories: (1) indices or ratios, comprising parameters obtained from a basic or comprehensive metabolic panel and/or derived from anthropometric measurements, and (2) circulating molecules implicated in pathophysiological processes associated with IR. Furthermore, numerous novel biomarkers, including markers of β-cell dysfunction, radiographic quantification of excess visceral adipose tissue, T2D prediction models, certain microRNAs and metabolomic biomarkers, have also provided promising preliminary results. This narrative review aims to present current evidence pertaining to the most notable and exciting biomarkers of IR that are under rigorous evaluation.