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The Association Between Insulin Use and Asthma: An Epidemiological Observational Analysis and Mendelian Randomization Study

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Abstract

Background

Asthma is a common respiratory disease caused by genetic and environmental factors, but the contribution of insulin use to the risk of asthma remains unclear. This study aimed to investigate the association between insulin use and asthma in a large population-based cohort, and further explore their causal relationship by Mendelian randomization (MR) analysis.

Methods

An epidemiological study including 85,887 participants from the National Health and Nutrition Examination Survey (NHANES) 2001–2018 was performed to evaluate the association between insulin use and asthma. Based on the inverse-variance weighted approach, MR analysis were conducted to estimate the causal effect of insulin use on asthma from the UKB and FinnGen datasets, respectively.

Results

In the NHANES cohort, we found that insulin use was associated with an increased risk of asthma [odd ratio (OR) 1.38; 95% CI 1.16–1.64; p < 0.001]. For the MR analysis, we found a causal relationship between insulin use and a higher risk of asthma in both Finn (OR 1.10; p < 0.001) and UK Biobank cohorts (OR 1.18; p < 0.001). Meanwhile, there was no causal association between diabetes and asthma. After multivariable adjustment for diabetes in UKB cohort, the insulin use remained significantly associated with an increased risk of asthma (OR 1.17, p < 0.001).

Conclusions

An association between insulin use and an increased risk of asthma was found via the real-world data from the NHANES. In addition, the current study identified a causal effect and provided a genetic evidence of insulin use and asthma. More studies are needed to elucidate the mechanisms underlying the association between insulin use and asthma.

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Data Availability

GWAS data are available through the MRC IEU Open GWAS database (https://gwas.mrcieu.ac.uk/). NHANES data are publicly available through the Center for Disease Control (https://wwwn.cdc.gov/nchs/nhanes/).

Abbreviations

MR:

Mendelian randomization

NHANES:

National Health and Nutrition Examination Survey

OR:

Odd ratio

SNPs:

Single nucleotide polymorphisms

PSU:

Primary sampling units

SE:

Standard errors

CDC:

Centers for Disease Control and Prevention

GWAS:

Genome-wide association studies

IEU:

Integrative Epidemiology Unit

UKB:

UK Biobank

LD:

Linkage disequilibrium

IVW:

Inverse variance weighting

MVMR:

Multivariable Mendelian randomization

CI:

Confidence intervals

Th2:

T helper type 2

T1DM:

Type 1 diabetes

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Acknowledgements

Not applicable.

Funding

This work was supported by the Incubation Program for Distinguished Young Scholars by Guangzhou Medical University (GMU2020-207).

Author information

Author notes

  1. Zikai Lin, Junfeng Huang and Shuojia Xie have contributed equally as co-first authors.

  2. Shiyue Li and Ruchong Chen have contributed equally to this article as corresponding authors and supervised the work.

Authors and Affiliations

  1. State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, Guangdong, China

    Zikai Lin, Junfeng Huang, Shuojia Xie, Ziwen Zheng, Kailun Tang, Shiyue Li & Ruchong Chen

  2. Nanshan School of Medical, Guangzhou Medical University, Guangzhou, China

    Zikai Lin & Shuojia Xie

  3. Department of Allergy and Clinical Immunology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China

    Kailun Tang & Ruchong Chen

  4. Clinical Medical College of Henan University, Kaifeng, China

    Kailun Tang

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Contributions

Study design: RC, SL, ZL, JH, SX; Data collection: JH, SX, ZZ; Data analyses: ZL, SX, TK; Results visualization: ZL, JH, Results interpretations: All authors; Manuscript writing: ZL, JH, SX; Manuscript revising: RC, SL. All authors approved the final version of the manuscript.

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Correspondence to Shiyue Li or Ruchong Chen.

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Lin, Z., Huang, J., Xie, S. et al. The Association Between Insulin Use and Asthma: An Epidemiological Observational Analysis and Mendelian Randomization Study. Lung 201, 189–199 (2023). https://doi.org/10.1007/s00408-023-00611-z

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