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Causal effects of inflammatory bowel disease on risk of type 2 diabetes: a two-sample multivariable Mendelian randomization study

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Abstract

Aim

This study aimed to explore the causal association between inflammatory bowel disease (IBD) and the risk of type 2 diabetes (T2D) based on a two-sample Mendelian randomization (MR) study.

Methods

Summary single nucleotide polymorphism (SNP)-phenotype association data were obtained from published two genome-wide association studies (GWAS) including SNPs related to IBD, UC, or CD in European participants (n = 71,997) and East Asian participants (n = 16,805). Two GWAS including SNPs associated with T2D included 655,666 Europeans and 433,540 East Asians. A series of screening processes were performed to select qualified instrumental SNPs strongly related to exposure. We applied the inverse variance weighted (IVW), the MR-Egger regression, and the weighted median to estimate the causal effects of IBD, ulcerative colitis (UC) or Crohn’ disease (CD) on T2D. Cochran’s Q test was conducted to evaluate the statistical heterogeneity between SNPs in the IVW method. The leave-one-out analysis was employed to assess whether the results were caused by any single SNP associated with IBD, UC, or CD. Odds ratio (OR) and 95% confidence interval (CI) were calculated.

Results

The IVW results demonstrated that IBD could increase the risk of T2D in the European population (OR = 1.0230, 95%CI: 1.0073–1.0390). UC was positively associated with the risk of T2D according to the weighted median (OR = 1.0274, 95%CI: 1.0009–1.0546) and IVW (OR = 1.0244, 95%CI: 1.0071–1.0421) results in the European population. The IVW results indicated that the CD was positively associated with the risk of T2D in the European population (OR = 1.0187, 95%CI: 1.0045–1.0330). In the East Asian population, there are no associations between the IBD, UC, or CD and the risk of T2D (all P > 0.05). MVMR results revealed that the causal effect UC on T2D was still statistically significant after including body mass index (BMI) or low-density lipoprotein (LDL).

Conclusion

IBD, UC, or CD had causal effects on the risk of T2D in the European population, which might provide evidence for the prevention of T2D in patients with IBD, UC, or CD.

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Data availability

The datasets generated and/or analyzed during the current study are available in the GWASs, https://gwas.mrcieu.ac.uk/datasets/.

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  1. Department of Digestive Internal Medicine, Lianyungang Hospital of Traditional Chinese Medicine, 160# Chaoyang Middle Road, Lianyungang, 222000, Jiangsu, China

    Yue Niu, Qing Zhang & Yinting Wei

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Contributions

YN and YW designed the study. YN wrote the manuscript. QZ collected, analyzed, and interpreted the data. YW critically reviewed, edited, and approved the manuscript. All authors read and approved the final manuscript.

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Correspondence to Yinting Wei.

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The requirement of ethical approval for this was waived by the Institutional Review Board of Lianyungang Hospital of Traditional Chinese Medicine, because the data were accessed from GWAS (a publicly available database).

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The need for written informed consent was waived by the Institutional Review Board of Lianyungang Hospital of Traditional Chinese Medicine due to retrospective nature of the study.

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Niu, Y., Zhang, Q. & Wei, Y. Causal effects of inflammatory bowel disease on risk of type 2 diabetes: a two-sample multivariable Mendelian randomization study. Acta Diabetol (2024). https://doi.org/10.1007/s00592-024-02254-9

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