Wang Hui, Wu Sensen, Pan Dikang, Ning Yachan, Fu Yanhong, Feng Chunjing, Guo Jianming, Liu Zichuan, Gu Yongquan
Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China.
School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 300072, China.
Nutr Diabetes. 2025 May 16;15(1):20. doi: 10.1038/s41387-025-00370-1.
BACKGROUND: This study aimed to investigate the role of Apolipoprotein B (Apo B) in diabetic nephropathy (DN) from epidemiological and genetic perspectives. METHODS: We employed weighted multivariable-adjusted logistic regression to assess the relationship between ApoB and DN risk, utilizing data from the National Health and Nutrition Examination Survey spanning 2007-2016. Then, we used restricted cubic splines (RCS) to flexibly model and visualize the relation of predicted ApoB levels with DN risk. Subsequently, a bidirectional two-sample Mendelian randomization study using genome-wide association study summary statistics was performed. The primary Inverse Variance Weighted method, along with supplementary MR approaches, was employed to verify the causal link between ApoB and DN. Sensitivity analyses were conducted to confirm the robustness of the results. RESULTS: Our observational study enrolled 2242 participants with diabetes mellitus from NHANES. The multivariable logistic regression model indicated that elevated ApoB levels (>1.2 g/L), compared to low levels (<0.8 g/L), were significantly associated with DN risk (P < 0.05). The RCS model revealed a positive linear association with the risk of DN when ApoB levels exceeded 1.12 g/L (OR = 1.29, 95% CI: 1.07-1.57, P = 0.008). However, the MR IVW method did not reveal a direct causal effect of DN on ApoB (OR: 0.976; 95% CI: 0.950-1.004; P = 0.095), nor a direct causal effect of ApoB on DN (OR: 0.837; 95% CI: 0.950-1.078; P = 0.428). CONCLUSION: The evidence from observational studies indicates a positive correlation between ApoB levels exceeding 1.12 g/L and the onset of DN. However, the causal effects of ApoB on DN and vice versa were not supported by the MR analysis.
背景：本研究旨在从流行病学和遗传学角度探讨载脂蛋白B（Apo B）在糖尿病肾病（DN）中的作用。 方法：我们采用加权多变量调整逻辑回归来评估ApoB与DN风险之间的关系，使用了2007 - 2016年美国国家健康与营养检查调查（NHANES）的数据。然后，我们使用受限立方样条（RCS）来灵活建模并可视化预测的ApoB水平与DN风险之间的关系。随后，进行了一项使用全基因组关联研究汇总统计数据的双向双样本孟德尔随机化研究。采用主要的逆方差加权方法以及补充的孟德尔随机化方法来验证ApoB与DN之间的因果关系。进行敏感性分析以确认结果的稳健性。 结果：我们的观察性研究纳入了来自NHANES的2242名糖尿病患者。多变量逻辑回归模型表明，与低水平（<0.8 g/L）相比，ApoB水平升高（>1.2 g/L）与DN风险显著相关（P < 0.05）。RCS模型显示，当ApoB水平超过1.12 g/L时，与DN风险呈正线性关联（OR = 1.29，95% CI：1.07 - 1.57，P = 0.008）。然而，孟德尔随机化逆方差加权方法未显示DN对ApoB有直接因果效应（OR：0.976；95% CI：0.950 - 1.004；P = 0.095），也未显示ApoB对DN有直接因果效应（OR：0.837；95% CI：0.950 - 1.078；P = 0.428）。 结论：观察性研究的证据表明，ApoB水平超过1.12 g/L与DN的发病呈正相关。然而，孟德尔随机化分析不支持ApoB对DN以及DN对ApoB的因果效应。
Diabetol Metab Syndr. 2025-3-26
Front Endocrinol (Lausanne). 2024
Diabetes Res Clin Pract. 2022-1
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