Li Huan, Shi Yulu, Zhang Hui, Han Jie, Zhang Xiaoping, Liu ZiJie
First Affiliated Hospital, Kunming Medical University, Kunming, China.
Yunnan Key Laboratory of Laboratory Medicine, Kunming, China.
Front Endocrinol (Lausanne). 2025 Aug 20;16:1652396. doi: 10.3389/fendo.2025.1652396. eCollection 2025.
Atherosclerotic cardiovascular disease (ASCVD) and diabetic kidney disease (DKD) are interconnected vascular complications in diabetes, with dyslipidemia playing a key role. The modifying effect of ASCVD on the lipid-DKD relationship in diabetic patients without lipid-lowering treatment remains unclear.
This retrospective study included 26,476 type 2 diabetic patients without lipid-lowering therapy. Associations between lipids (LDL-C, TC, TG, HDL-C) and DKD risk were analyzed using regression and restricted cubic spline (RCS) curves analysis. Both multiplicative and additive interactions between lipids and ASCVD were assessed.
HDL-C showed a significant linear association with DKD. RCS analyses revealed distinct patterns based on ASCVD status: significant threshold effects for LDL-C (2.68 mmol/L), TC (4.29 mmol/L), TG (2.48 mmol/L), and HDL-C (1.64 mmol/L) on DKD risk were observed only in diabetic patients without ASCVD. No significant nonlinear threshold effects were found for LDL-C, TC, HDL-C on DKD risk in diabetic patients with ASCVD. LDL-C and TC showed continuous increases in DKD risk without a discernible safe threshold in diabetic patients with ASCVD. Crucially, a strong synergistic interaction existed between ASCVD and both TC (RERI=7.46, AP=0.25, SI=1.34) and LDL-C (RERI=9.91, AP=0.27, SI=1.38), significantly amplifying their adverse effects on renal injury.
ASCVD amplifies the detrimental renal effects of TC and LDL-C and eliminates protective lipid thresholds in diabetic patients. Consequently, lipid management in diabetic patients should be individualized: strict control of TC and LDL-C is prioritized for those with ASCVD, while consideration of lipid threshold effects is key for those without ASCVD.
动脉粥样硬化性心血管疾病（ASCVD）和糖尿病肾病（DKD）是糖尿病中相互关联的血管并发症，血脂异常起着关键作用。在未接受降脂治疗的糖尿病患者中，ASCVD对脂质与DKD关系的调节作用尚不清楚。
这项回顾性研究纳入了26476例未接受降脂治疗的2型糖尿病患者。使用回归分析和受限立方样条（RCS）曲线分析脂质（低密度脂蛋白胆固醇、总胆固醇、甘油三酯、高密度脂蛋白胆固醇）与DKD风险之间的关联。评估了脂质与ASCVD之间的乘法和加法相互作用。
高密度脂蛋白胆固醇与DKD呈显著线性关联。RCS分析根据ASCVD状态显示出不同模式：仅在无ASCVD的糖尿病患者中观察到低密度脂蛋白胆固醇（2.68 mmol/L）、总胆固醇（4.29 mmol/L）、甘油三酯（2.48 mmol/L）和高密度脂蛋白胆固醇（1.64 mmol/L）对DKD风险有显著阈值效应。在有ASCVD的糖尿病患者中，未发现低密度脂蛋白胆固醇、总胆固醇、高密度脂蛋白胆固醇对DKD风险有显著非线性阈值效应。在有ASCVD的糖尿病患者中，低密度脂蛋白胆固醇和总胆固醇的DKD风险持续增加，没有明显的安全阈值。至关重要的是，ASCVD与总胆固醇（相对超额危险度增加率=7.46，归因比例=0.25，协同指数=1.34）和低密度脂蛋白胆固醇（相对超额危险度增加率=9.91，归因比例=0.27，协同指数=1.38）之间存在强烈的协同相互作用，显著放大了它们对肾损伤的不良影响。
ASCVD放大了总胆固醇和低密度脂蛋白胆固醇对糖尿病患者肾脏的有害影响，并消除了脂质阈值的保护作用。因此，糖尿病患者的血脂管理应个体化：对于有ASCVD的患者，优先严格控制总胆固醇和低密度脂蛋白胆固醇，而对于无ASCVD的患者，考虑脂质阈值效应是关键。
