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慢性阻塞性肺疾病与糖尿病之间的潜在因果关系:一项双向两样本孟德尔随机化研究

Potential Causal Relationship Between Chronic Obstructive Pulmonary Disease and Diabetes: A Bidirectional Two-Sample Mendelian Randomization Study.

作者信息

Wang Xinyan, Chen Xin, Feng Ruizhi, Jiang Hongli, Liu Wei

机构信息

Division of Internal Medicine, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.

Department of Integrated Traditional Chinese and Western Medicine, Zigong First People's Hospital, Zigong, 643000, People's Republic of China.

出版信息

Int J Chron Obstruct Pulmon Dis. 2025 Jul 4;20:2259-2272. doi: 10.2147/COPD.S516346. eCollection 2025.


DOI:10.2147/COPD.S516346
PMID:40630676
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12236365/
Abstract

PURPOSE: Diabetes, particularly type 2 diabetes (T2D), is a common comorbidity that occurs at a higher frequency in chronic obstructive pulmonary disease (COPD) patients compared to the general population. The COPD-diabetes association is documented epidemiologically and experimentally. Potential mechanisms, including systemic inflammation and metabolic dysregulation, are discussed as plausible pathways. However, their causal relationship still needs to be confirmed. METHODS: We conducted a comprehensive bidirectional two-sample Mendelian randomization (MR) analysis to evaluate the causal links between COPD and both type 1 diabetes (T1D) and T2D by using genome-wide association study (GWAS) summary statistics in European and Asian populations. By employing MR methods, the causal effect of diabetes on the risk of COPD as well as specific COPD-related clinical outcomes, including COPD with infections (COPD-I), pneumonia or pneumonia-derived septicaemia, chronic opportunistic infections, respiratory insufficiency, hospital admissions, and onset age (early or late) were explored. RESULTS: Forward MR analysis provided evidence consistent with a causal relationship between T2D and an increased risk of COPD in the European population (IVW odds ratio (OR): 1.002, 95% confidence interval (CI): 1.001-1.003, = 0.001). This association appeared consistent with MR Egger analysis, yielding a similar result for European COPD patients (MR Egger OR: 1.108, 95% CI: 1.016 -1.208, = 0.021). No statistically conclusive evidence of a causal relationship between diabetes and COPD was found in the Asian population. Besides, genetically determined T1D was identified as a risk factor for the incidence of COPD-I in the European-specific population (IVW OR: 1.017, 95% CI: 1.009-1.025, < 0.001). The reverse MR analysis, exploring the effect of COPD on the risk of diabetes, did not achieve consistent results in either the European or Asian populations. CONCLUSION: This study suggested a modest but statistically significant causal association between T2D and COPD in individuals of European ancestry. Further explorations are required to better understand the underlying mechanisms linking diabetes to COPD development.

摘要

目的:糖尿病,尤其是2型糖尿病(T2D),是一种常见的合并症,与普通人群相比,慢性阻塞性肺疾病(COPD)患者中其发生频率更高。COPD与糖尿病之间的关联已在流行病学和实验中得到证实。包括全身炎症和代谢失调在内的潜在机制被认为是可能的途径。然而,它们之间的因果关系仍需确认。 方法:我们进行了一项全面的双向两样本孟德尔随机化(MR)分析,通过使用欧洲和亚洲人群的全基因组关联研究(GWAS)汇总统计数据,评估COPD与1型糖尿病(T1D)和T2D之间的因果联系。采用MR方法,探讨了糖尿病对COPD风险以及特定COPD相关临床结局的因果效应,包括合并感染的COPD(COPD-I)、肺炎或肺炎源性败血症、慢性机会性感染、呼吸功能不全、住院以及发病年龄(早发或晚发)。 结果:正向MR分析提供的证据表明,在欧洲人群中T2D与COPD风险增加之间存在因果关系(逆方差加权比值比(OR):1.002,95%置信区间(CI):1.001 - 1.003,P = 0.001)。这种关联在MR Egger分析中似乎也一致,欧洲COPD患者得到了类似结果(MR Egger OR:1.108,95% CI:1.016 - 1.208,P = 0.021)。在亚洲人群中未发现糖尿病与COPD之间存在因果关系的统计学确凿证据。此外,在欧洲特定人群中,基因决定的T1D被确定为COPD-I发病的一个风险因素(逆方差加权OR:1.017,95% CI:1.009 - 1.025,P < 0.001)。探索COPD对糖尿病风险影响的反向MR分析在欧洲或亚洲人群中均未得到一致结果。 结论:本研究表明,在欧洲血统个体中,T2D与COPD之间存在适度但具有统计学意义的因果关联。需要进一步探索以更好地理解将糖尿病与COPD发展联系起来的潜在机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5278/12236365/6e6dc6ecc88f/COPD-20-2259-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5278/12236365/7155e480dbfa/COPD-20-2259-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5278/12236365/6e6dc6ecc88f/COPD-20-2259-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5278/12236365/7155e480dbfa/COPD-20-2259-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5278/12236365/6e6dc6ecc88f/COPD-20-2259-g0002.jpg

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本文引用的文献

[1]
INTEGRATING MENDELIAN RANDOMIZATION WITH CAUSAL MEDIATION ANALYSES FOR CHARACTERIZING DIRECT AND INDIRECT EXPOSURE-TO-OUTCOME EFFECTS.

Ann Appl Stat. 2024-9

[2]
Genetically Determined Circulating Saturated and Unsaturated Fatty Acids and the Occurrence and Exacerbation of Chronic Obstructive Pulmonary Disease-A Two-Sample Mendelian Randomization Study.

Nutrients. 2024-8-14

[3]
COPD and T2DM: a Mendelian randomization study.

Front Endocrinol (Lausanne). 2024

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Front Endocrinol (Lausanne). 2023

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J Endocr Soc. 2023-6-26

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Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk.

Nat Genet. 2023-3

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Nature. 2023-1

[8]
Evaluating the role of non-alcoholic fatty liver disease in cardiovascular diseases and type 2 diabetes: a Mendelian randomization study in Europeans and East Asians.

Int J Epidemiol. 2023-6-6

[9]
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Am J Manag Care. 2022-9-1

[10]
Mechanisms Linking COPD to Type 1 and 2 Diabetes Mellitus: Is There a Relationship between Diabetes and COPD?

Medicina (Kaunas). 2022-8-1

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