Liu Yi-Ying, Zhang Yue-Yang, Wan Qin
Centre for Endocrine and Thyroid Diseases, Deyang People's Hospital, Deyang, 618000, China.
Department of Endocrinology and Metabolism, Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
Endocr Metab Immune Disord Drug Targets. 2025 May 19. doi: 10.2174/0118715303380282250225071730.
Observational studies suggest an association between the immune system and type 2 diabetes. The present study sought to ascertain the causal relationship between BDH1 and type 2 diabetes and investigate whether immunocytes mediate this relationship.
Appropriate single nucleotide polymorphisms (SNPs) were carefully selected from publicly available GWAS databases based on rigorous criteria to ensure the validity of the Mendelian randomization (MR) analysis. Inverse variance weighting (IVW) was employed as the primary approach for assessing effect sizes, supplemented by four sensitivity analysis techniques: weighted median, simple mode, weighted mode, and MR-Egger regression tests, all aimed at ensuring the robustness and reliability of the IVW results. Reverse MR was conducted to confirm the feasibility of the mediation analysis. Lastly, Cochran's Q test, MR Egger intercept regression, and MR-PRESSO analysis were utilized to examine heterogeneity and horizontal pleiotropy.
The expression of BDH1 is inversely associated with the risk of type 2 diabetes, with an odds ratio of 0.97 (95% CI: 0.95-0.99). IgD+ CD38+ B cell absolute count (20.7%), HLA DR on dendritic cell (18.7%), BAFF-R on CD20- CD38- B cell (9.5%), CD25 on IgD+ CD24+ B cell (4.1%), and BAFF-R on IgD+ B cell (3.4%), all exhibit certain mediating effects, whereas IgD+ CD38+ B cell absolute count, activated and resting CD4 regulatory T cell %, CD4+ T cell, transitional B cell absolute count, CD28- CD8 dim T cell absolute count, CD45 on HLA DR+ CD8+ T cell, FSC-A on HLA DR+ natural killer, and SSC-A on plasmacytoid dendritic cell exert masking effects.
The findings indicate that immunocytes could serve as a crucial mediating mechanism through which BDH1 exerts its protective effect against type 2 diabetes, offering novel insights for the prevention and therapeutic management of the disease.
观察性研究表明免疫系统与2型糖尿病之间存在关联。本研究旨在确定BDH1与2型糖尿病之间的因果关系，并调查免疫细胞是否介导这种关系。
基于严格标准从公开可用的全基因组关联研究（GWAS）数据库中精心挑选合适的单核苷酸多态性（SNP），以确保孟德尔随机化（MR）分析的有效性。采用逆方差加权（IVW）作为评估效应大小的主要方法，并辅以四种敏感性分析技术：加权中位数、简单模式、加权模式和MR-Egger回归检验，所有这些技术均旨在确保IVW结果的稳健性和可靠性。进行反向MR以确认中介分析的可行性。最后，利用 Cochr an's Q检验、MR Egger截距回归和MR-PRESSO分析来检验异质性和水平多效性。
BDH1的表达与2型糖尿病风险呈负相关，优势比为0.97（95%CI：0.95 - 0.99）。IgD + CD38 + B细胞绝对计数（20.7%）、树突状细胞上的HLA DR（18.7%）、CD20 - CD38 - B细胞上的BAFF-R（9.5%）、IgD + CD24 + B细胞上的CD25（4.1%）以及IgD + B细胞上的BAFF-R（3.4%）均表现出一定的中介作用，而IgD + CD38 + B细胞绝对计数、活化和静息CD4调节性T细胞百分比、CD4 + T细胞、过渡性B细胞绝对计数、CD28 - CD8 dim T细胞绝对计数、HLA DR + CD8 + T细胞上的CD45、HLA DR + 自然杀伤细胞上的FSC-A以及浆细胞样树突状细胞上的SSC-A发挥掩盖作用。
研究结果表明免疫细胞可能是BDH1对2型糖尿病发挥保护作用的关键中介机制，为该疾病的预防和治疗管理提供了新的见解。
