Supplementary Material for: Estimating Glucose Disposal Rate and Its Association with All-Cause and Etiologically Specific Mortality in Cardiovascular-Kidney-Metabolic Syndrome Among U.S. Adults: Insights from NHANES 1999-2018

Background: The estimated glucose disposal rate (eGDR) is a useful indicator of insulin resistance (IR). This study explores its association with cardiovascular-kidney-metabolic syndrome (CKM), a relationship that has been rarely investigated. The aim of this research is to examine potential correlations between eGDR and CKM.
Methods: We analyzed data from the National Health and Nutrition Examination Survey (NHANES) conducted between 1999–2018. eGDR was categorized into three quartiles: Q1, Q2 and Q3. Weighted multivariate cox regression models, competing risk models and restricted cubic spline (RCS) models were applied to investigate the association between eGDR and mortality outcomes, including all-cause and cause-specific mortality. Subgroup analyse was performed to test the robustness of the results.
Results: Of the 14,074 patients with CKM, 2,426 died, including 767 from cardio−cerebrovascular disease and 39 from kidney disease. After adjustment for all potential confounders, weighted multivariate cox models showed that eGDR was inversely associated with mortality from all causes and with mortality from cardio−cerebrovascular (P < 0.05), but not with mortality from kidney disease (P >0.05). The RCS model further confirmed the linear relationship between eGDR all-cause, cardio−cerebrovascular, with statistical evidence supporting this (P for nonlinear > 0.05). Even when using non-cardiovascular-cerebrovascular mortality as a competitive risk, the adjusted Fine-Gray model demonstrated that eGDR remains an independent predictor of cardiovascular-cerebrovascular mortality (SHR 0.560, 95% CI 0.460–0.680, P < 0.001).
Conclusion: Our findings reveal a significant inverse association between eGDR and the risk of both all-cause and cardio-cerebrovascular mortality in patients with CKM. This suggests that higher levels of eGDR are linked to a lower risk of death from these causes, indicating that improving insulin sensitivity may have protective effects on survival outcomes in CKM patients.

研究背景：估算葡萄糖处置率（estimated glucose disposal rate，eGDR）是评估胰岛素抵抗（insulin resistance，IR）的有效指标。目前针对eGDR与心血管-肾脏-代谢综合征（cardiovascular-kidney-metabolic syndrome，CKM）之间关联的研究较为匮乏，本研究旨在探讨二者之间的潜在相关性。
研究方法：本研究分析了1999-2018年美国国家健康与营养检查调查（National Health and Nutrition Examination Survey，NHANES）的数据。将eGDR划分为三个四分位数组：Q1、Q2及Q3。采用加权多因素Cox回归模型、竞争风险模型及限制性立方样条（restricted cubic spline，RCS）模型，分析eGDR与全因死亡及特定病因死亡等结局的关联。通过亚组分析验证研究结果的稳健性。
研究结果：在14074名CKM患者中，共有2426例死亡，其中767例死于心脑血管疾病，39例死于肾脏疾病。在校正所有潜在混杂因素后，加权多因素Cox模型结果显示，eGDR与全因死亡及心脑血管疾病死亡呈负相关（P<0.05），但与肾脏疾病死亡无显著关联（P>0.05）。限制性立方样条模型进一步证实，eGDR与全因死亡、心脑血管死亡之间存在线性关联，非线性检验P>0.05。即便以非心脑血管死亡作为竞争风险，校正后的Fine-Gray模型仍显示，eGDR是心脑血管死亡的独立预测因素（亚分布风险比SHR=0.560，95%置信区间CI：0.460~0.680，P<0.001）。
研究结论：本研究结果显示，在CKM患者中，eGDR与全因死亡及心脑血管死亡风险均呈显著负相关。这表明较高的eGDR水平对应较低的上述原因死亡风险，提示改善胰岛素敏感性可能对CKM患者的生存结局具有保护作用。