Frontiers in endocrinology · 2026
The triglyceride-glucose index modulates the association between diabetes duration and insulin resistance in type 2 diabetes: a large cross-sectional study.
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Dong Ya, Huang Xiaohong, Hao Mingyu, Li Haiyan, Yan Dewen
Аннотация
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, P interaction = 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.
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, P interaction = 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.