Type 1 Diabetes and Cataracts: Investigating Mediating Effects of Serum Metabolites Using Bidirectional Mendelian Randomization.

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Metabolites Pub Date : 2024-11-20 DOI:10.3390/metabo14110644

Yumeng Shi, Jingxi Qin, Yankai Li, Jin Yang, Yi Lu

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引用次数: 0

Abstract

Purpose: To investigate the causal relationship between type 1 diabetes (T1D) and cataracts and to explore the mediating role of serum metabolites.

Methods: This study employed bidirectional Mendelian randomization (MR) using genetic variants as instrumental variables to infer causality in both directions: from T1D to cataracts and cataracts to T1D. Genetic data for T1D, its complications, and cataracts were sourced from independent genome-wide association study (GWAS) datasets. A two-step multivariable MR combined with mediation analysis was conducted to evaluate the indirect effects of serum metabolites in the causal pathway from T1D to cataracts.

Results: The MR analysis demonstrated a significant causal association between T1D and an increased risk of cataracts (OR = 1.01-1.05; p < 0.05). Further analysis showed that patients with T1D complications such as coma, ketoacidosis, nephropathy, and retinopathy exhibited a significantly higher risk of developing cataracts compared to those without complications. Sensitivity analyses upheld the robustness of these findings, with no evidence of heterogeneity or pleiotropy. Additionally, 102 serum metabolites were found to exhibit statistically significant mediation effects on cataract risk, with four (13-HODE + 9-HODE, 2-naphthol sulfate, docosadienoate (22:2n6), and X-12906) showing significant mediation effects. Specifically, 13-HODE + 9-HODE had a protective effect, while the other three metabolites were linked to an increased cataract risk.

Conclusions: This study provides strong evidence of a causal link between T1D and cataracts, highlighting the mediating role of specific serum metabolites. These findings underscore the importance of early detection and management of cataracts in patients with T1D and suggest potential therapeutic targets for mitigating cataract risk. Further research should focus on replicating these findings in diverse populations and exploring the underlying metabolic pathways in greater detail.

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1 型糖尿病与白内障：利用双向孟德尔随机化研究血清代谢物的中介效应

目的：研究1型糖尿病（T1D）与白内障之间的因果关系，并探讨血清代谢物的中介作用：本研究采用双向孟德尔随机化（MR）方法，将遗传变异作为工具变量，从两个方向推断因果关系：从 T1D 到白内障，以及从白内障到 T1D。T1D、其并发症和白内障的遗传数据来自独立的全基因组关联研究（GWAS）数据集。通过两步多变量 MR 结合中介分析，评估了血清代谢物在 T1D 到白内障的因果关系中的间接影响：MR分析表明，T1D与白内障风险增加之间存在明显的因果关系（OR = 1.01-1.05; p < 0.05）。进一步分析表明，与无并发症的患者相比，患有昏迷、酮症酸中毒、肾病和视网膜病变等T1D并发症的患者患白内障的风险明显更高。敏感性分析证实了这些发现的可靠性，没有证据表明存在异质性或多重性。此外，研究还发现 102 种血清代谢物对白内障风险具有统计学意义上的中介效应，其中 4 种（13-HODE + 9-HODE、2-萘酚硫酸盐、二十二碳二烯酸酯（22:2n6）和 X-12906）具有显著的中介效应。具体来说，13-HODE + 9-HODE具有保护作用，而其他三种代谢物则与白内障风险增加有关：这项研究有力地证明了 T1D 与白内障之间的因果关系，并强调了特定血清代谢物的中介作用。这些发现强调了早期发现和治疗 T1D 患者白内障的重要性，并提出了降低白内障风险的潜在治疗目标。进一步的研究应侧重于在不同人群中复制这些发现，并更详细地探索潜在的代谢途径。

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

Metabolites Biochemistry, Genetics and Molecular Biology-Molecular Biology

CiteScore

5.70

自引率

7.30%

发文量

1070

审稿时长

17.17 days

期刊介绍： Metabolites (ISSN 2218-1989) is an international, peer-reviewed open access journal of metabolism and metabolomics. Metabolites publishes original research articles and review articles in all molecular aspects of metabolism relevant to the fields of metabolomics, metabolic biochemistry, computational and systems biology, biotechnology and medicine, with a particular focus on the biological roles of metabolites and small molecule biomarkers. Metabolites encourages scientists to publish their experimental and theoretical results in as much detail as possible. Therefore, there is no restriction on article length. Sufficient experimental details must be provided to enable the results to be accurately reproduced. Electronic material representing additional figures, materials and methods explanation, or supporting results and evidence can be submitted with the main manuscript as supplementary material.