The triglyceride-glucose index modulates the association between diabetes duration and insulin resistance in type 2 diabetes: a large cross-sectional study.

Background: The longitudinal impact of diabetes duration on the progression of insulin resistance (IR) in type 2 diabetes (T2DM) remains to be fully elucidated. It is also unclear whether this relationship is uniform across all patients or modified by specific metabolic factors. Objective: To investigate the association between diabetes duration and IR, and to identify critical effect modifiers that define high-risk trajectories. Methods: This cross-sectional study enrolled 3,309 patients with T2DM, categorized into non-IR (HOMA-IR < 2.31, n = 1,530) and IR (HOMA-IR ≥ 2.31, n = 1,779) groups. Multivariable linear regression was used to assess the independent association between diabetes duration and HOMA-IR. Subgroup and interaction analyses were performed to identify effect modifiers. A two-piecewise linear regression model was employed to delineate threshold effects. Results: In the overall cohort, diabetes duration was independently associated with higher HOMA-IR after full adjustment (β = 0.04, 95% CI: 0.03-0.05, Conclusions: This study defines a novel, actionable high-risk phenotype in T2DM, characterized by a combination of a TyG index ≥ 9.187 and diabetes duration exceeding 4.0 years, which is associated with a markedly accelerated increase in IR. Given that the TyG index is adjustable, this framework provides a clinically meaningful, personalized strategy for targeted early intervention, enabling precise prevention for those most susceptible to worsening insulin resistance.