Association of diabetic nephropathy with lipid metabolism: a Mendelian randomization study
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 explo...
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| Format: | Article |
| Language: | English |
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BMC
2025-03-01
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| Series: | Diabetology & Metabolic Syndrome |
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| Online Access: | https://doi.org/10.1186/s13098-025-01641-8 |
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| author | Pengfei Xie Weinan Xie Zhaobo Wang Ziwei Guo Rumeng Tang Haoyu Yang Yu Wei Ling Zhou Yishan Huang Linhua Zhao Lili Zhang |
| author_facet | Pengfei Xie Weinan Xie Zhaobo Wang Ziwei Guo Rumeng Tang Haoyu Yang Yu Wei Ling Zhou Yishan Huang Linhua Zhao Lili Zhang |
| author_sort | Pengfei Xie |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-58e2b64009c4425c90aaa653aefcd43a |
| institution | DOAJ |
| issn | 1758-5996 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Diabetology & Metabolic Syndrome |
| spelling | doaj-art-58e2b64009c4425c90aaa653aefcd43a2025-08-20T02:49:25ZengBMCDiabetology & Metabolic Syndrome1758-59962025-03-0117111610.1186/s13098-025-01641-8Association of diabetic nephropathy with lipid metabolism: a Mendelian randomization studyPengfei Xie0Weinan Xie1Zhaobo Wang2Ziwei Guo3Rumeng Tang4Haoyu Yang5Yu Wei6Ling Zhou7Yishan Huang8Linhua Zhao9Lili Zhang10Institute of Metabolic Diseases, Guang’anmen Hospital, China Academy of Chinese Medical SciencesInstitute of Metabolic Diseases, Guang’anmen Hospital, China Academy of Chinese Medical SciencesInstitute of Metabolic Diseases, Guang’anmen Hospital, China Academy of Chinese Medical SciencesInstitute of Metabolic Diseases, Guang’anmen Hospital, China Academy of Chinese Medical SciencesInstitute of Metabolic Diseases, Guang’anmen Hospital, China Academy of Chinese Medical SciencesInstitute of Metabolic Diseases, Guang’anmen Hospital, China Academy of Chinese Medical SciencesInstitute of Metabolic Diseases, Guang’anmen Hospital, China Academy of Chinese Medical SciencesInstitute of Metabolic Diseases, Guang’anmen Hospital, China Academy of Chinese Medical SciencesChina-Japan Friendship HospitalInstitute of Metabolic Diseases, Guang’anmen Hospital, China Academy of Chinese Medical SciencesInstitute of Metabolic Diseases, Guang’anmen Hospital, China Academy of Chinese Medical SciencesAbstract 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.https://doi.org/10.1186/s13098-025-01641-8Lipid profileDiabetic nephropathyUrine albumin-to-creatinine ratioMendelian randomization |
| spellingShingle | Pengfei Xie Weinan Xie Zhaobo Wang Ziwei Guo Rumeng Tang Haoyu Yang Yu Wei Ling Zhou Yishan Huang Linhua Zhao Lili Zhang Association of diabetic nephropathy with lipid metabolism: a Mendelian randomization study Diabetology & Metabolic Syndrome Lipid profile Diabetic nephropathy Urine albumin-to-creatinine ratio Mendelian randomization |
| title | Association of diabetic nephropathy with lipid metabolism: a Mendelian randomization study |
| title_full | Association of diabetic nephropathy with lipid metabolism: a Mendelian randomization study |
| title_fullStr | Association of diabetic nephropathy with lipid metabolism: a Mendelian randomization study |
| title_full_unstemmed | Association of diabetic nephropathy with lipid metabolism: a Mendelian randomization study |
| title_short | Association of diabetic nephropathy with lipid metabolism: a Mendelian randomization study |
| title_sort | association of diabetic nephropathy with lipid metabolism a mendelian randomization study |
| topic | Lipid profile Diabetic nephropathy Urine albumin-to-creatinine ratio Mendelian randomization |
| url | https://doi.org/10.1186/s13098-025-01641-8 |
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