Type 2 diabetes and Inflammatory Bowel Disease: A Bidirectional Two-sample Mendelian Randomization Study

Abstract

Abstract Background Studies have shown that patients with inflammatory bowel diseases (IBD) coexisting with type 2 diabetes mellitus (T2DM) have higher risk of infection, increased healthcare utilization and decreased quality of life, while currently they are not treated with more effective immunosuppressive therapy. Observational studies have shown a bidirectional association between T2DM and IBD, including Crohn's disease (CD) and ulcerative colitis (UC). However, because of the difficulty in determining sequential timeliness, it is unclear whether the observed associations are causal. We investigated the association between T2DM and IBD by bidirectional two-sample Mendelian randomization (MR) to clarify the casual relationship.Methods Independent genetic variants for T2DM and IBD were selected as instruments from published genome-wide association studies (GWAS), mainly in European ancestry. Instrumental variables (IVs) associated with T2DM and IBD were extracted separately from the largest GWAS meta-analysis. MR analyses included inverse variance weighting, weighted median estimator, MR Egger regression, and sensitivity analyses with Steiger filtering and MR PRESSO.Results Genetically predicted T2DM (per log-odds ratio increase) was associated with risk for IBD. In the data samples for UC (6968 cases, 20464 controls) and CD (5956 cases, 14927 controls), the odds ratio [95% confidence interval] for T2DM on UC and CD were 0.882 (0.826,0.942), and 0.955(0.877,1.038), respectively. In contrast, among 62,892 patients with T2DM, no genetically influenced association between IBD and T2DM was observed.Conclusions The results of the bidirectional MR Study suggest that T2DM has a negative causal effect on UC, which provides implications for clinical treatment decisions in IBD patients with T2DM. The findings do not support a causal relationship between T2DM and CD, UC and T2DM, or CD and T2DM, and the impact of IBD on T2DM needs further investigation.