糖尿病肾病与脂质代谢的关联：一项孟德尔随机化研究

Association of diabetic nephropathy with lipid metabolism: a Mendelian randomization study.

作者信息

Xie Pengfei, Xie Weinan, Wang Zhaobo, Guo Ziwei, Tang Rumeng, Yang Haoyu, Wei Yu, Zhou Ling, Huang Yishan, Zhao Linhua, Zhang Lili

机构信息

Institute of Metabolic Diseases, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China.

Graduate College, Beijing University of Traditional Chinese Medicine, Beijing, 100029, China.

出版信息

Diabetol Metab Syndr. 2025 Mar 26;17(1):102. doi: 10.1186/s13098-025-01641-8.

DOI:10.1186/s13098-025-01641-8

PMID:40133980

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11938690/

Abstract

OBJECTIVE

Patients with diabetic nephropathy (DN) often present with lipid profile abnormalities. While associations between these parameters and DN have been suggested, confounding factors obscure causal relationships. This study employed bidirectional Mendelian randomization (MR) to explore these links.

METHODS

Using genome-wide association study (GWAS) data, the primary analysis used the inverse-variance weighted (IVW) method, which was supported by MR-Egger regression and a weighted median estimator (WME). Sensitivity analyses, including heterogeneity, pleiotropy tests, leave-one-out, and reverse causality analyses, were conducted.

RESULTS

The IVW model revealed the following: (1) causal relationships between triglycerides (TG) (OR: 1.5807, 95% CI: 1.2578-1.9865, P = 0.0001), high-density lipoprotein cholesterol (HDL-C) (OR: 0.7342, 95% CI: 0.5729-0.9409, P = 0.0146), and apolipoprotein A1 (ApoA1) (OR: 0.6506, 95% CI: 0.5190-0.8156, P = 0.0002) and DN; (2) causal relationships between TG (OR: 1.0607, 95% CI: 1.0143-1.1093, P = 0.0098), HDL-C (OR: 0.9453, 95% CI: 0.9053-1.9871, P = 0.0109), and apolipoprotein B (ApoB) (OR: 1.0672, 95% CI: 0.0070-1.1310, P = 0.0280) and the urinary albumin-creatinine ratio (UACR); (3) no causal relationship between total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), ApoB and DN, or between TC, LDL-C, ApoA1 and UACR; (4) none of the results showed reverse causality.

CONCLUSION

TG is a risk factor for DN and UACR; HDL-C is protective for both; ApoA1 protects against DN; and ApoB is a risk factor for UACR. To further explore the underlying mechanisms between TG, HDL-C, ApoA1, ApoB, and their associations with DN and UACR, and to provide reference for the selection of lipid management and treatment strategies for clinical DN patients. This study demonstrated that causal relationships between TG, HDL-C, and ApoA1 with DN and between TG, HDL-C, and ApoB with the UACR.

摘要

目的

糖尿病肾病（DN）患者常出现血脂异常。虽然已表明这些参数与DN之间存在关联，但混杂因素掩盖了因果关系。本研究采用双向孟德尔随机化（MR）来探究这些联系。

方法

利用全基因组关联研究（GWAS）数据，主要分析采用逆方差加权（IVW）方法，并得到MR-Egger回归和加权中位数估计器（WME）的支持。进行了敏感性分析，包括异质性、多效性检验、留一法和反向因果关系分析。

结果

IVW模型显示如下结果：（1）甘油三酯（TG）（比值比：1.5807，95%置信区间：1.2578 - 1.9865，P = 0.0001）、高密度脂蛋白胆固醇（HDL-C）（比值比：0.7342，95%置信区间：0.5729 - 0.9409，P = 0.0146）和载脂蛋白A1（ApoA1）（比值比：0.6506，95%置信区间：0.5190 - 0.8156，P = 0.0002）与DN之间存在因果关系；（2）TG（比值比：1.0607，95%置信区间：1.0143 - 1.1093，P = 0.0098）、HDL-C（比值比：0.9453，95%置信区间：0.9053 - 1.9871，P = 0.0109）和载脂蛋白B（ApoB）（比值比：1.0672，95%置信区间：0.0070 - 1.1310，P = 0.0280）与尿白蛋白肌酐比值（UACR）之间存在因果关系；（3）总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、ApoB与DN之间，或TC、LDL-C、ApoA1与UACR之间不存在因果关系；（4）所有结果均未显示反向因果关系。

结论

TG是DN和UACR的危险因素；HDL-C对二者均有保护作用；ApoA1可预防DN；ApoB是UACR的危险因素。为进一步探究TG、HDL-C、ApoA1、ApoB之间的潜在机制及其与DN和UACR的关联，并为临床DN患者血脂管理和治疗策略的选择提供参考。本研究证明了TG与HDL-C、ApoA1与DN之间以及TG与HDL-C、ApoB与UACR之间的因果关系。