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

## TL;DR

This study shows that the triglyceride-glucose (TyG) index affects how diabetes duration influences insulin resistance in type 2 diabetes patients.

## Contribution

The study identifies a high-risk T2DM phenotype defined by TyG index and diabetes duration, offering a personalized strategy for early intervention.

## Key findings

- Diabetes duration is linked to increased insulin resistance only in patients already insulin resistant.
- The TyG index significantly modifies the relationship between diabetes duration and insulin resistance.
- A sharp increase in insulin resistance occurs after 4 years of diabetes in patients with high TyG index.

## Abstract

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.

To investigate the association between diabetes duration and IR, and to identify critical effect modifiers that define high-risk trajectories.

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.

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, P < 0.001). This association was significant only in the IR group (β = 0.04, 95% CI: 0.02-0.06, P < 0.001) and absent in the non-IR group. Subgroup analysis revealed that the TyG index was the only significant effect modifier (βinteraction = 0.06, 95% CI: 0.02-0.09, Pinteraction = 0.001). Crucially, a threshold effect was identified in the high-TyG group: HOMA-IR increased sharply by 0.08 per additional year of diabetes only after 4.0 years (P < 0.001).

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.