Department of Oncology, Key Laboratory of Cancer Molecular and Translational Research, The Affiliated Hospital of Qingdao University, Qingdao, China.
Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, China.
Diabetes Obes Metab. 2024 Sep;26(9):3552-3564. doi: 10.1111/dom.15694. Epub 2024 Jun 9.
To investigate the associations of metabolic score for insulin resistance (METS-IR) with all-cause and cardiovascular disease (CVD)-specific mortality and the potential mediating role of biological ageing.
A cohort of 19 204 participants from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 was recruited for this study. Cox regression models, restricted cubic splines, and Kaplan-Meier survival curves were used to determine the relationships of METS-IR with all-cause and CVD-specific mortality. Mediation analyses were performed to explore the possible intermediary role of biological ageing markers, including phenotypic age (PhenoAge) and biological age (BioAge).
During a median follow-up of 9.17 years, we observed 2818 deaths, of which 875 were CVD-specific. Multivariable Cox regression showed that the highest METS-IR level (Q4) was associated with increased all-cause (hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.14-1.67) and CVD mortality (HR 1.52, 95% CI 1.10-2.12) compared with the Q1 level. Restricted cubic splines showed a nonlinear relationship between METS-IR and all-cause mortality. Only METS-IR above the threshold (41.02 μg/L) was positively correlated with all-cause death. METS-IR had a linear positive relationship with CVD mortality. In mediation analyses, we found that PhenoAge mediated 51.32% (p < 0.001) and 41.77% (p < 0.001) of the association between METS-IR and all-cause and CVD-specific mortality, respectively. For BioAge, the mediating proportions of PhenoAge were 21.33% (p < 0.001) and 15.88% (p < 0.001), respectively.
This study highlights the detrimental effects of insulin resistance, as measured by METS-IR, on all-cause and CVD mortality. Moreover, it underscores the role of biological ageing in mediating these associations, emphasizing the need for interventions targeting both insulin resistance and ageing processes to mitigate mortality risks in metabolic disorders.
探讨胰岛素抵抗代谢评分（METS-IR）与全因和心血管疾病（CVD）特异性死亡率的关系，以及生物老化的潜在中介作用。
本研究纳入了 1999 年至 2018 年全国健康和营养调查（NHANES）的 19204 名参与者。使用 Cox 回归模型、限制三次样条和 Kaplan-Meier 生存曲线来确定 METS-IR 与全因和 CVD 特异性死亡率的关系。进行中介分析以探讨生物老化标志物（包括表型年龄（PhenoAge）和生物年龄（BioAge））的可能中介作用。
在中位数为 9.17 年的随访期间，我们观察到 2818 例死亡，其中 875 例为 CVD 特异性死亡。多变量 Cox 回归显示，与 METS-IR 水平最低的 Q1 相比，METS-IR 最高的 Q4 水平与全因（危险比 [HR] 1.38，95%置信区间 [CI] 1.14-1.67）和 CVD 死亡率（HR 1.52，95%CI 1.10-2.12）增加相关。限制三次样条显示 METS-IR 与全因死亡率之间存在非线性关系。只有高于阈值（41.02μg/L）的 METS-IR 与全因死亡呈正相关。METS-IR 与 CVD 死亡率呈线性正相关。在中介分析中，我们发现 PhenoAge 分别介导了 METS-IR 与全因和 CVD 特异性死亡率之间 51.32%（p<0.001）和 41.77%（p<0.001）的关联。对于 BioAge，PhenoAge 的中介比例分别为 21.33%（p<0.001）和 15.88%（p<0.001）。
本研究强调了胰岛素抵抗（通过 METS-IR 测量）对全因和 CVD 死亡率的有害影响。此外，它强调了生物老化在介导这些关联中的作用，强调需要针对胰岛素抵抗和老化过程进行干预，以降低代谢紊乱患者的死亡风险。
