{"title":"Association of diabetic nephropathy with lipid metabolism: a Mendelian randomization study.","authors":"Pengfei Xie, Weinan Xie, Zhaobo Wang, Ziwei Guo, Rumeng Tang, Haoyu Yang, Yu Wei, Ling Zhou, Yishan Huang, Linhua Zhao, Lili Zhang","doi":"10.1186/s13098-025-01641-8","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"17 1","pages":"102"},"PeriodicalIF":3.4000,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938690/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diabetology & Metabolic Syndrome","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13098-025-01641-8","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
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.
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.