脂质是肾功能与糖尿病风险之间缺失的环节吗？基于队列研究的中介分析见解。

Is Lipid a Missing Link Between Renal Function and Diabetes Risk? Insights from a Mediation Analysis Based on the Cohort Study.

作者信息

Liang Xiaomin, Hu Haofei, Li Ying, Gui Shuiqing

机构信息

Department of Critical Care Medicine, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, 518000, People's Republic of China.

Department of Nephrology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, 518000, People's Republic of China.

出版信息

J Multidiscip Healthc. 2025 Sep 6;18:5635-5649. doi: 10.2147/JMDH.S544229. eCollection 2025.

DOI:10.2147/JMDH.S544229

PMID:40950562

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12423442/

Abstract

PURPOSE

Both renal function impairment and lipid abnormalities are recognized risk factors for diabetes. However, the potential mediating role of lipid parameters in the relationship between renal function and diabetes risk remains unexplored. This study aimed to investigate whether and to what extent lipid parameters mediate the association between renal function and diabetes risk.

PATIENTS AND METHODS

We conducted a cohort study including adults from 32 sites across 11 Chinese cities between 2010 and 2016. Renal function was assessed by estimated glomerular filtration rate (eGFR). Lipid parameters included triglyceride glucose (TyG), triglyceride glucose- body mass index (TyG-BMI), triglyceride/ high-density lipoprotein cholesterol (TG/HDL-c), and atherogenic index of plasma (AIP). Cox proportional hazards models were used to examine the relationship between eGFR and diabetes risk. Subgroup analyses were performed to identify potential effect modifiers. Mediation analyses quantified the proportion of eGFR's effect on diabetes risk mediated through each lipid parameter.

RESULTS

Among 115,488 participants (54.07% male, mean age 44.12 ± 12.95 years) followed for 3.10 ± 0.95 years, 2659 (2.30%) developed diabetes. After multivariable adjustment, higher eGFR was inversely associated with diabetes risk (HR=0.98, 95% CI: 0.98-0.98). This association was more pronounced in females, participants <60 years, those with BMI <25 kg/m², SBP <140 mmHg, non-smokers, non-drinkers, ALT <40 U/L, and AST <40 U/L. Mediation analyses revealed that TyG, TyG-BMI, TG/HDL-c, and AIP mediated 23.14%, 21.05%, 3.54%, and 12.49% of the eGFR-diabetes relationship, respectively.

CONCLUSION

Reduced renal function, as indicated by lower eGFR, is associated with increased diabetes risk. This relationship is partially mediated through lipid metabolism pathways, suggesting lipid may represent a missing link between renal function and diabetes risk.

摘要

目的

肾功能损害和脂质异常均被认为是糖尿病的危险因素。然而，脂质参数在肾功能与糖尿病风险关系中的潜在中介作用仍未得到探索。本研究旨在调查脂质参数是否以及在多大程度上介导肾功能与糖尿病风险之间的关联。

患者与方法

我们进行了一项队列研究，纳入了2010年至2016年间来自中国11个城市32个地点的成年人。通过估计肾小球滤过率（eGFR）评估肾功能。脂质参数包括甘油三酯葡萄糖（TyG）、甘油三酯葡萄糖-体重指数（TyG-BMI）、甘油三酯/高密度脂蛋白胆固醇（TG/HDL-c）和血浆致动脉粥样硬化指数（AIP）。采用Cox比例风险模型来检验eGFR与糖尿病风险之间的关系。进行亚组分析以确定潜在的效应修饰因素。中介分析量化了通过每个脂质参数介导的eGFR对糖尿病风险影响的比例。

结果

在115,488名参与者（男性占54.07%，平均年龄44.12±12.95岁）中随访了3.10±0.95年，2659人（2.30%）患糖尿病。多变量调整后，较高的eGFR与糖尿病风险呈负相关（HR=0.98，95%CI：0.98 - 0.98）。这种关联在女性、年龄<60岁的参与者、BMI<25kg/m²者、收缩压<140mmHg者、非吸烟者、不饮酒者、谷丙转氨酶<40U/L者和谷草转氨酶<40U/L者中更为明显。中介分析显示，TyG、TyG-BMI、TG/HDL-c和AIP分别介导了eGFR与糖尿病关系的23.14%、21.05%、3.54%和12.49%。