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Background <p>Insulin resistance (IR) is mechanistically linked to hypertension, yet no study has directly compared fasting-insulin-based and non-insulin-based IR surrogates for predicting mortality across the glycemic spectrum in hypertensive adults. We evaluated ten IR indices, three insulin-based [homeostasis model assessment of insulin resistance (HOMA-IR), McAuley index, and quantitative insulin sensitivity check index (QUICKI)] and seven non-insulin-based [triglyceride-glucose index (TyG), stress hyperglycemia ratio (SHR), cardiometabolic index (CMI), atherogenic index of plasma (AIP), estimated glucose disposal rate (eGDR), metabolic score for insulin resistance (METS-IR), and lipid accumulation product (LAP)], for all-cause mortality (ACM) and cardiovascular mortality (CVM) by glycemic status.</p> Methods <p>This prospective cohort study included 7,548 hypertensive adults from NHANES 1999–2018, classified as normoglycemia (<i>n</i> = 1,869), prediabetes (<i>n</i> = 3,389), and diabetes (<i>n</i> = 2,290). Mortality data were collected through December 31, 2019. Associations were analyzed using Cox models with three levels of adjustment. Dose-response relationships were modeled with restricted cubic splines.</p> Results <p>Over a mean follow-up of 8.7 ± 5.3 years, 1,752 ACM events (23.2%) and 499 CVM events (6.6%) occurred. In fully adjusted models, HOMA-IR independently predicted ACM (per-unit HR 1.017; Q4 HR 1.165) and CVM (per-unit HR 1.012). eGDR showed the strongest overall associations: ACM: per-unit HR 0.807; Q4 HR 0.559; CVM: per-unit HR 0.774; Q4 HR 0.538. TyG predicted ACM (per-unit HR 1.158; Q4 HR 1.233) and CVM per-unit (HR 1.160). In glycemic-stratified analyses, HOMA-IR was the only index with per-unit ACM significance across all three strata (normoglycemia: HR 1.085; prediabetes: HR 1.039; diabetes: HR 1.012). eGDR showed per-unit and Q4 ACM significance in prediabetes and diabetes, and demonstrated significant quartile-level protection for CVM in both prediabetes (Q4 HR 0.465) and diabetes (Q4 HR 0.463), whereas per-unit associations with CVM were observed only in diabetes. TyG was significantly associated with ACM in diabetes (per-unit HR 1.147; Q4 HR 1.337) and with CVM in diabetes (Q4 HR 1.595).</p> Conclusions <p>In hypertensive adults, HOMA-IR was the only fasting-insulin-based index independently associated with ACM across all three glycemic strata. eGDR demonstrated the most consistent non-insulin-based associations with ACM and CVM, particularly in prediabetes and diabetes. TyG provided additional prognostic value for ACM and CVM, particularly in patients with diabetes. These findings support selecting IR indices based on glycemic phenotype and data availability.</p> Graphical abstract

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Head-to-head comparison of fasting-insulin-based versus non-insulin-based insulin resistance surrogates for predicting all-cause and cardiovascular mortality in hypertensive adults across the glycemic continuum: a prospective cohort study

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  • 发表日期：

    2026年6月15日

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  • Fuad A. Abdu,
  • Abdul-Quddus Mohammed,
  • Wen Zhang,
  • Jiasuer Alifu,
  • Lu Liu,
  • Guoqing Yin,
  • Yiteng Liao,
  • Guofu Zhu,
  • Wenliang Che

摘要

Background

Insulin resistance (IR) is mechanistically linked to hypertension, yet no study has directly compared fasting-insulin-based and non-insulin-based IR surrogates for predicting mortality across the glycemic spectrum in hypertensive adults. We evaluated ten IR indices, three insulin-based [homeostasis model assessment of insulin resistance (HOMA-IR), McAuley index, and quantitative insulin sensitivity check index (QUICKI)] and seven non-insulin-based [triglyceride-glucose index (TyG), stress hyperglycemia ratio (SHR), cardiometabolic index (CMI), atherogenic index of plasma (AIP), estimated glucose disposal rate (eGDR), metabolic score for insulin resistance (METS-IR), and lipid accumulation product (LAP)], for all-cause mortality (ACM) and cardiovascular mortality (CVM) by glycemic status.

Methods

This prospective cohort study included 7,548 hypertensive adults from NHANES 1999–2018, classified as normoglycemia (n = 1,869), prediabetes (n = 3,389), and diabetes (n = 2,290). Mortality data were collected through December 31, 2019. Associations were analyzed using Cox models with three levels of adjustment. Dose-response relationships were modeled with restricted cubic splines.

Results

Over a mean follow-up of 8.7 ± 5.3 years, 1,752 ACM events (23.2%) and 499 CVM events (6.6%) occurred. In fully adjusted models, HOMA-IR independently predicted ACM (per-unit HR 1.017; Q4 HR 1.165) and CVM (per-unit HR 1.012). eGDR showed the strongest overall associations: ACM: per-unit HR 0.807; Q4 HR 0.559; CVM: per-unit HR 0.774; Q4 HR 0.538. TyG predicted ACM (per-unit HR 1.158; Q4 HR 1.233) and CVM per-unit (HR 1.160). In glycemic-stratified analyses, HOMA-IR was the only index with per-unit ACM significance across all three strata (normoglycemia: HR 1.085; prediabetes: HR 1.039; diabetes: HR 1.012). eGDR showed per-unit and Q4 ACM significance in prediabetes and diabetes, and demonstrated significant quartile-level protection for CVM in both prediabetes (Q4 HR 0.465) and diabetes (Q4 HR 0.463), whereas per-unit associations with CVM were observed only in diabetes. TyG was significantly associated with ACM in diabetes (per-unit HR 1.147; Q4 HR 1.337) and with CVM in diabetes (Q4 HR 1.595).

Conclusions

In hypertensive adults, HOMA-IR was the only fasting-insulin-based index independently associated with ACM across all three glycemic strata. eGDR demonstrated the most consistent non-insulin-based associations with ACM and CVM, particularly in prediabetes and diabetes. TyG provided additional prognostic value for ACM and CVM, particularly in patients with diabetes. These findings support selecting IR indices based on glycemic phenotype and data availability.

Graphical abstract