氧化平衡与糖尿病成年人的糖尿病肾病及死亡率相关：来自美国国家健康与营养检查调查（NHANES）数据库及孟德尔随机化研究的见解
Oxidative balance is associated with diabetic kidney disease and mortality in adults with diabetes mellitus: Insights from NHANES database and Mendelian randomization.
作者信息
Jiang Li, Jian Jie, Sai Xulin, Yu Hongda, Liang Wanxian, Wu Xiai
机构信息
Diabetes Department of Integrated Chinese and Western Medicine, China-Japan Friendship Hospital, Beijing, China.
China National Center for Integrated Traditional Chinese and Western Medicine, Beijing, China.
出版信息
J Diabetes Investig. 2025 Mar;16(3):451-462. doi: 10.1111/jdi.14390. Epub 2024 Dec 26.
OBJECTIVE
To explore and validate the association between the oxidative balance and prevalence of diabetic kidney disease (DKD) and mortality in patients with diabetes.
STUDY DESIGN
A large and representative sample from the National Health and Nutrition Examination Survey (NHANES) from 2013 to 2016 was analyzed to study the potential association between Oxidative Balance Score (OBS) and prognosis of DKD in adult diabetic patients. Weighted multivariate logistic regression analysis was conducted to examine the relationship between OBS and DKD risk. Subgroup analysis, sensitivity analysis, and mediation effect analysis were conducted to explore the effect of the covariates and assess the robustness of the findings. Mendelian randomization (MR) was employed to evaluate the correlated relationship between mitochondrial reactive oxygen species (ROS) levels and DKD at the genetic level.
RESULT
The highest OBS quartile showed the most significant negative correlation with DKD compared to the lowest OBS quartile (OR = 0.62, 95% CI 0.41-0.92, P = 0.017). Higher OBS was associated with a reduced risk of DKD (OR = 0.96; 95% CI = 0.93, 0.98; P < 0.001) and mortality (P = 0.021 by log-rank) in diabetic patients. This association remained robust even after excluding individual OBS components. Subgroup analysis revealed the interaction of metabolic syndrome on OBS was significant. Mediation analyses revealed that OBS's effect on DKD was independent of blood uric acid and cholesterol. Restricted cubic spline (RCS) analysis indicated a typical L-shaped relationship between OBS and DKD risk. The physical activity was identified as the core variable predicting DKD risk by two machine learning algorithms. MR showed a potential correlated relationship between ROS and microalbuminuria in DKD.
CONCLUSIONS
The high level of oxidative balance score was negatively correlated with the risk of DKD and mortality in diabetic patients.
目的
探讨并验证氧化平衡与糖尿病肾病（DKD）患病率及糖尿病患者死亡率之间的关联。
研究设计
分析2013年至2016年美国国家健康与营养检查调查（NHANES）中的一个具有代表性的大样本，以研究氧化平衡评分（OBS）与成年糖尿病患者DKD预后之间的潜在关联。进行加权多变量逻辑回归分析，以检验OBS与DKD风险之间的关系。进行亚组分析、敏感性分析和中介效应分析，以探讨协变量的影响并评估研究结果的稳健性。采用孟德尔随机化（MR）方法在基因水平评估线粒体活性氧（ROS）水平与DKD之间的相关关系。
结果
与最低OBS四分位数相比，最高OBS四分位数与DKD的负相关性最为显著（OR = 0.62，95% CI 0.41 - 0.92，P = 0.017）。较高的OBS与糖尿病患者DKD风险降低（OR = 0.96；95% CI = 0.93，0.98；P < 0.001）及死亡率降低（对数秩检验P = 0.021）相关。即使排除单个OBS成分后，这种关联仍然稳健。亚组分析显示代谢综合征对OBS的交互作用显著。中介分析表明，OBS对DKD的影响独立于血尿酸和胆固醇。限制立方样条（RCS）分析表明OBS与DKD风险之间呈典型的L形关系。通过两种机器学习算法确定身体活动是预测DKD风险的核心变量。MR显示ROS与DKD中的微量白蛋白尿之间存在潜在的相关关系。
结论
氧化平衡评分高与糖尿病患者DKD风险及死亡率呈负相关。
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