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

IF 3.4 3区医学 Q2 ENDOCRINOLOGY & METABOLISM

Diabetology & Metabolic Syndrome Pub Date : 2025-03-26 DOI:10.1186/s13098-025-01641-8

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

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引用次数: 0

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.

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糖尿病肾病与脂质代谢的关系：一项孟德尔随机研究。

目的：糖尿病肾病（DN）患者常表现为血脂异常。虽然这些参数与DN之间存在关联，但混淆因素模糊了因果关系。本研究采用双向孟德尔随机化（MR）来探索这些联系。方法：利用全基因组关联研究（GWAS）数据，采用反方差加权（IVW）方法进行初步分析，并采用MR-Egger回归和加权中位数估计（WME）进行支持。进行敏感性分析，包括异质性、多效性检验、遗漏和反向因果分析。结果：IVW模型显示：(1)甘油三酯（TG）（OR: 1.5807, 95% CI: 1.2578 ~ 1.9865, P = 0.0001）、高密度脂蛋白胆固醇（HDL-C）（OR: 0.7342, 95% CI: 0.5729 ~ 0.9409, P = 0.0146）、载脂蛋白A1 (ApoA1) （OR: 0.6506, 95% CI: 0.5190 ~ 0.8156, P = 0.0002）与DN之间存在因果关系；(2) 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）、载脂蛋白B (ApoB) （OR: 1.0672, 95% CI: 0.0070 ~ 1.1310, P = 0.0280）与尿白蛋白-肌酐比（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和DN之间无因果关系，TC、LDL-C、ApoA1与UACR之间无因果关系；(4)结果均不存在反向因果关系。结论：TG是DN和UACR的危险因素；HDL-C对两者都有保护作用；ApoA1保护DN；载脂蛋白b是UACR的危险因素。进一步探讨TG、HDL-C、ApoA1、ApoB与DN和UACR的关系及其潜在机制，为临床DN患者脂质管理和治疗策略的选择提供参考。本研究证实TG、HDL-C和ApoA1与DN之间存在因果关系，TG、HDL-C和ApoB与UACR之间存在因果关系。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Diabetology & Metabolic Syndrome ENDOCRINOLOGY & METABOLISM-

CiteScore

6.20

自引率

0.00%

发文量

170

审稿时长

7.5 months

期刊介绍： Diabetology & Metabolic Syndrome publishes articles on all aspects of the pathophysiology of diabetes and metabolic syndrome. By publishing original material exploring any area of laboratory, animal or clinical research into diabetes and metabolic syndrome, the journal offers a high-visibility forum for new insights and discussions into the issues of importance to the relevant community.