中华中医药学刊

炎症因子指标介导高脂血症与2型糖尿病因果关系的两样本双向孟德尔随机化研究

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毛清雯 , 石岩 , 杨宇峰

中华中医药学刊 | 国家项目点击 2026,44(3): 114-119

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中华中医药学刊 |国家项目点击 2026 , 44 (3) : 114 -119

炎症因子指标介导高脂血症与2型糖尿病因果关系的两样本双向孟德尔随机化研究

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毛清雯, 石岩, 杨宇峰

作者信息

辽宁中医药大学，辽宁沈阳 110847

通讯作者:

石岩（1963 -），男，辽宁沈阳人，教授，博士研究生导师，博士，研究方向：糖尿病及代谢综合征中西医结合基础与临床。E-mail：shi_yan0705@163.com

杨宇峰（1979 -），男，辽宁凌源人，教授，硕士研究生导师，博士，研究方向：糖尿病及代谢综合征中西医结合基础与临床。E-mail：yangyufeng5698@163.com。

作者简介:

毛清雯（1997 -），女，辽宁沈阳人，博士在读，研究方向：中医内科学。

Mediating Effect of Inflammatory Factor Indicators on Causal Relationship Between Hyperlipidemia and Type 2 Diabetes by Two-Sample Bidirectional Mendelian Randomization

Qingwen MAO, Yan SHI, Yufeng YANG

Affiliations

Liaoning University of Traditional Chinese Medicine, Shenyang 110032, Liaoning, China

出版时间: 2026-03-10 doi: 10.13193/j.issn.1673-7717.2026.03.022

文章导航

摘要

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目的

借助孟德尔随机化（Mendelian Randomization，MR）方法，探究高脂血症与2型糖尿病间的遗传关联，明确循环炎症因子在二者关系里的潜在中介作用。

方法

运用公开全基因组关联研究（Genome-wide association study，GWAS）数据，高脂血症数据源自GCST90475724（含436 724例，其中病例17 425例），2型糖尿病数据取自LOH P R等人针对468 298例欧洲人群的研究，炎症因子数据源于TRAYLOR M的血浆蛋白质组研究（筛选出91个可分析的炎症因子）。通过两样本双向MR分析评估高脂血症与2型糖尿病的总效应，采用两步MR法开展中介分析：先确定高脂血症对炎症因子的因果效应，再评估炎症因子对2型糖尿病的影响，进而量化直接效应与中介效应。工具变量单核苷酸多态性（single nucleotide polymorphisms，SNPs）选取以P < 5 × 10^-8为显著关联标准，经连锁不平衡筛选（R² < 0.001，阈值10 000 kb）及F统计量（> 10）保障工具变量有效性。以逆方差加权（inverse variance weighted，IVW）为主要分析方法，辅以最大似然法、加权中位数法、MR-Egger回归及MR-PRESSO等敏感性分析验证结果稳健性。

结果

高脂血症与2型糖尿病存在显著关联（OR = 1.748，95% CI = 1.013-3.015，P = 0.044），且无显著异质性与水平基因多效性。中介分析发现7种炎症因子与2型糖尿病相关，其中成纤维细胞生长因子21（fibroblast growth factor21，FGF21，OR = 1.595，P = 0.009）为风险因素，成纤维细胞生长因子19（fibroblast growth factor19，FGF19，OR = 0.807，P = 0.001）为保护因素。进一步分析表明，白细胞介素-4（Interleukin-4，IL-4，OR = 1.089，P = 0.012）和FGF19（OR = 0.863，P = 0.043）或可作为中介因子，参与高脂血症对2型糖尿病的因果路径。

结论

研究揭示高脂血症与2型糖尿病的遗传因果关系，证实特定炎症因子在两者关联中的中介作用。同时，中医药在治疗两疾病中发挥重要作用，为通过调控炎症因子预防或治疗2型糖尿病提供遗传学证据及重要手段。

关键词

高脂血症 / 2型糖尿病 / 孟德尔随机化 / 炎症因子 / 中介效应 / 遗传关联 / 公开全基因组关联研究（Genome-wide association study，GWAS） / 中医药

Abstract

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Objective

To explore the genetic association between hyperlipidemia and type 2 diabetes mellitus using the Mendelian randomization（MR）method, and to clarify the potential mediating role of circulating inflammatory factors in the relationship between them.

Methods

Public Genome-wide association study（GWAS）data was used. The hyperlipidemia data was obtained from GCST90475724（including 436 724 cases, with 17 425 cases of hyperlipidemia）. The T2DM data was from a study by Loh PR and other authors on 468 298 European individuals. The inflammatory factor data was derived from the plasma proteome study by TRAYLOR M（91 analyzable inflammatory factors were screened out）. A two-sample bidirectional MR analysis was conducted to evaluate the total effect between hyperlipidemia and T2DM. A two-step MR method was used for mediation analysis. First, the causal effect of hyperlipidemia on inflammatory factors was determined, and then the impact of inflammatory factors on T2DM was assessed, so as to quantify the direct effect and mediating effect. For the selection of instrumental variables single nucleotide polymorphisms（SNPs）, a significant association criterion of P < 5 × 10^-8 was adopted. Linkage disequilibrium screening（R² < 0.001, threshold of 10 000 kb）and F-statistic（> 10）were used to ensure the validity of instrumental variables. The inverse variance weighting（IVW）was used as the main analysis method, supplemented by sensitivity analyses such as maximum likelihood method, weighted median method, MR-Egger regression and MR-PRESSO to verify the robustness of the results.

Results

There was a significant association between hyperlipidemia and T2DM（OR = 1.748, 95% CI = 1.013-3.015, P = 0.044）, and there was no significant heterogeneity or horizontal pleiotropy. Mediation analysis found that 7 inflammatory factors were associated with T2DM. Among them, fibroblast growth factor 21（FGF21, OR = 1.595, P = 0.009）was a risk factor, and fibroblast growth factor 19（FGF19, OR = 0.807, P = 0.001）was a protective factor. Further analysis showed that interleukin-4（IL-4, OR = 1.089, P = 0.012）and FGF19（OR = 0.863, P = 0.043）might act as mediating factors and participate in the causal pathway from hyperlipidemia to T2DM.

Conclusion

This study reveals the genetic causal relationship between hyperlipidemia and T2DM, confirms the mediating role of specific inflammatory factors in the association between the two. At the same time, traditional Chinese medicine plays an important role in the treatment of both diseases, providing genetic evidence and important means for preventing or treating T2DM by regulating inflammatory factors.

Key words

hyperlipidemia / type 2 diabetes mellitus / Mendelian randomization / inflammatory factor / mediating effect / genetic association / GWAS / traditional Chinese medicine

引用本文

毛清雯, 石岩, 杨宇峰. 炎症因子指标介导高脂血症与2型糖尿病因果关系的两样本双向孟德尔随机化研究. 中华中医药学刊, 2026 , 44 (3) : 114 -119 . DOI: 10.13193/j.issn.1673-7717.2026.03.022

Qingwen MAO, Yan SHI, Yufeng YANG. Mediating Effect of Inflammatory Factor Indicators on Causal Relationship Between Hyperlipidemia and Type 2 Diabetes by Two-Sample Bidirectional Mendelian Randomization[J]. Chinese Archives of Traditional Chinese Medicine, 2026 , 44 (3) : 114 -119 . DOI: 10.13193/j.issn.1673-7717.2026.03.022

基金

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国家中医药管理局青年岐黄学者项目(国中医药人教函［2022］256号)
辽宁省中央引导地方科技发展专项-辽宁省糖尿病中医病证结合重点实验室(2019JH6/10200009)
辽宁省科技计划联合计划自然科学基金项目(2024-BSLH-152)
辽宁省科学技术计划项目(2023JH2/101300050)
辽宁省教育厅高校基本科研项目(JYTZD2023197)

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2026年第44卷第3期

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doi: 10.13193/j.issn.1673-7717.2026.03.022

首发时间：2026-10-14
出版时间：2026-03-10

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基金

国家中医药管理局青年岐黄学者项目(国中医药人教函［2022］256号)

辽宁省中央引导地方科技发展专项-辽宁省糖尿病中医病证结合重点实验室(2019JH6/10200009)

辽宁省科技计划联合计划自然科学基金项目(2024-BSLH-152)

辽宁省科学技术计划项目(2023JH2/101300050)

辽宁省教育厅高校基本科研项目(JYTZD2023197)

作者信息

辽宁中医药大学，辽宁沈阳 110847

通讯作者:

石岩（1963 -），男，辽宁沈阳人，教授，博士研究生导师，博士，研究方向：糖尿病及代谢综合征中西医结合基础与临床。E-mail：shi_yan0705@163.com

杨宇峰（1979 -），男，辽宁凌源人，教授，硕士研究生导师，博士，研究方向：糖尿病及代谢综合征中西医结合基础与临床。E-mail：yangyufeng5698@163.com。

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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