CLINICAL TRIAL article
Front. Endocrinol.
Sec. Clinical Diabetes
The Triglyceride-Glucose Index Modulates the Association Between Diabetes Duration and Insulin Resistance in Type 2 Diabetes: A Large Cross-Sectional Study
Provisionally accepted
- 1Shenzhen Second People's Hospital, Shenzhen, China
- 2Shenzhen Bao'an Shiyan People's Hospital, Shen Zhen, China
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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, 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). 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.
Keywords: Diabetes duration, Homeostatic model assessment of insulin resistance (HOMA-IR), Insulin resistance (IR), Triglyceride-glucose index (TyG index), Type 2 diabetes mellitus (T2DM)
Received: 07 Dec 2025; Accepted: 02 Feb 2026.
Copyright: © 2026 Dong, Huang, Hao, Li and Yan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Haiyan Li
Dewen Yan
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