Estimated glucose disposal rate and its dual role in hyperlipidemia risk and mortality: a secondary analysis of retrospective cohort data from U.S. and Chinese

Wei et al. Lipids in Health and Disease (2025) 24:266 https://doi.org/10.1186/s12944-025-02684-6 Lipids in Health and Disease Open Access RESEARCH Estimated glucose disposal rate and its dual role in hyperlipidemia risk and mortality: a secondary analysis of retrospective cohort data from U.S. and Chinese Shouxin Wei1*†, Sijia Yu2†, Chuan Qian1†, Zhengwen Xu1, Yindong Jia1 and Bo Chen3* Abstract Background Hyperlipidemia is a major global public health issue and a significant risk factor for various chronic diseases, including cardiovascular disease and diabetes. Insulin resistance (IR) is closely associated with hyperlipidemia. Estimated glucose disposal rate (eGDR), a non-invasive tool for assessing IR, may have clinical utility in identifying hyperlipidemia and predicting its prognosis. Methods This study is a secondary analysis of retrospective cohort data based on publicly available databases, specifically the U.S. National Health and Nutrition Examination Survey (NHANES) and the China Health and Retirement Longitudinal Study (CHARLS)—incorporating both cross-sectional and longitudinal follow-up data to systematically evaluate the relationship between eGDR and the risk of hyperlipidemia and mortality. Multivariable weighted logistic regression models were employed to analyze the risk of hyperlipidemia, while Cox proportional hazards models were used to assess all-cause and cardiovascular disease (CVD) mortality. Generalized additive models and smooth curve fitting were applied to identify potential nonlinear relationships, and subgroup as well as sensitivity analyses were conducted to verify the robustness of the findings. Results In the NHANES cohort, each standard deviation increase in eGDR was associated with a 11.5% reduction in the risk of hyperlipidemia (OR = 0.885 [0.867, 0.903]), an 8.6% reduction in all-cause mortality (HR = 0.914 [0.892, 0.936]), and a 10.4% reduction in CVD mortality (HR = 0.896 [0.859, 0.936]). In the CHARLS cohort, each SD increase in eGDR was associated with a 7.1% reduction in the risk of hyperlipidemia (OR = 0.929 [0.905, 0.954]) and an 9.2% reduction in all-cause mortality (HR = 0.908 [0.869,0.949]). A nonlinear inverse relationship was observed between eGDR and the risk of hyperlipidemia, with evidence of a significant threshold effect. Kaplan–Meier survival curves demonstrated significantly lower all-cause and CVD mortality among individuals with higher eGDR levels. Stratified analyses † Shouxin Wei, Sijia Yu and Chuan Qian contributed equally. *Correspondence: Shouxin Wei Bo Chen Full list of author information is available at the end of the article © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creati vecommons.org/licenses/by-nc-nd/4.0/. Wei et al. Lipids in Health and Disease (2025) 24:266 Page 2 of 16 indicated that eGDR showed strong consistency and predictive value across different population subgroups, with particularly pronounced effects observed among younger individuals and those with diabetes. Conclusion Our study demonstrates that eGDR, as an indicator of insulin sensitivity, is significantly associated with the risk of hyperlipidemia and mortality, including both all-cause and CVD mortality. Improving eGDR levels may help reduce the health burden associated with hyperlipidemia and supports its potential clinical application in hyperlipidemia management and metabolic disease risk assessment. Keywords Estimated glucose disposal rate, Hyperlipidemia, Insulin resistance, Mortality, NHANES, CHARLS Introduction Hyperlipidemia is a common metabolic disorder characterized by abnormally elevated plasma lipid levels [1]. As a major risk factor for various chronic conditions— including cardiovascular disease (CVD) and diabetes— hyperlipidemia not only imposes a significant disease burden but is also associated with numerous adverse health outcomes, severely compromising patients’ quality of life and life expectancy [2, 3]. From 1999 to 2020, the age-adjusted mortality rate of hyperlipidemia-related cardiovascular disease in the United States rose from 36.33 to 99.77 per 1,000,000, with higher mortality observed among males, non-Hispanic populations, rural residents, and Black individuals [4]. Epidemiological studies indicate that with continued global socioeconom ic development, the prevalence of hyperlipidemia is steadily increasing, presenting a major challenge to global public health [5]. Current treatment strategies primarily rely on lifestyle modifications and pharmacotherapy. However, individual responses to treatment vary considerably, and medications may induce adverse effects that reduce adherence and diminish therapeutic efficacy [6, 7]. Although multiple treatment options exist, there remains an urgent need to develop more effective intervention strategies and clearly defined therapeutic targets to optimize clinical outcomes in patients with hyperlipidemia. The association between insulin resistance (IR) and hyperlipidemia has been widely documented. Hyperlipidemia is typically characterized by elevated plasma levels of triglycerides and low-density lipoprotein cholesterol (LDL-C), along with reduced high-density lipoprotein cholesterol (HDL-C). Studies have shown that IR contributes to the development of hyperlipidemia by disrupting the metabolism of triglycerides, HDL-C, LDL-C, and very-low-density lipoprotein cholesterol (VLDL-C) [8]. Saori et al. [9] reported that reduced insulin sensitivity is closely linked to altered expression of lipid metabolismrelated genes in skeletal muscle, suggesting that disrupted lipid handling in muscle may play a critical role in IR-mediated dyslipidemia. Similarly, Mamatha et al. [10] emphasized that the molecular mechanisms underlying hyperlipidemia are strongly associated with IR and the broader spectrum of metabolic dysfunction. Various techniques are available to assess IR. The hyperinsulinemic-euglycemic clamp (HIEC) is considered the gold standard but is invasive and labor-intensive, limiting its feasibility in large-scal (...truncated)