Bridging lipidic and endocrine insulin resistance pathways: association of an integrated insulin resistance index with long-term mortality in a coronary angiography cohort
A P Moissl-Blanke, G E Delgado, B K Kraemer, D Duerschmied, W Maerz, M E KleberAbstract
Background
Insulin resistance (IR) is associated with lipid metabolism disorders, glucose intolerance, and cardiovascular disease. The triglyceride glucose (TyG) index and homeostasis model assessment of insulin resistance (HOMA2-IR) reflect distinct metabolic and endocrine dimensions of IR. However, these indices capture only single components of a complex metabolic phenotype. Whether integrating complementary pathways of IR improves prognostic discrimination in patients at cardiovascular risk remains unclear.
Purpose
To evaluate the associations of TyG, HOMA2-IR, and a novel integrated insulin resistance index (iIR), combining fasting glucose, triglycerides, and insulin, with long-term all-cause and cardiovascular mortality.
Methods
We analysed 3,245 individuals (mean age 62.7±10.6 years; 69.7% men) undergoing coronary angiography with a median follow-up of 10 years. The iIR was constructed as a standardised composite of fasting glucose, triglycerides, and insulin. Cox proportional hazards models estimated hazard ratios (HRs) for a 1-standard-deviation increase, adjusted for age, sex, BMI, renal function, diabetes, hypertension, smoking, LDL cholesterol, and coronary artery disease status.
Results
In fully adjusted models, iIR was independently associated with all-cause mortality (HR 1.11, 95% CI 1.03–1.19; p=0.0047) and cardiovascular mortality (HR 1.10, 95% CI 1.01–1.21; p=0.028). TyG remained associated with all-cause mortality only (HR 1.08, 95% CI 1.01–1.16; p=0.021), whereas HOMA2-IR was not independently associated with either endpoint (all-cause HR 1.04, 95% CI 0.98–1.10; cardiovascular HR 1.01, 95% CI 0.93–1.09).
Conclusions
An integrated assessment of insulin resistance combining lipidic and endocrine components provides more consistent prognostic information than established single-pathway indices. Integrative characterisation of insulin resistance may enhance cardiometabolic risk stratification beyond conventional single-pathway markers.Fully adjusted HR for iIR