# No causal relationship between glucose and inflammatory bowel disease: a bidirectional two-sample mendelian randomization study

## TL;DR

This study finds no evidence that high glucose levels cause inflammatory bowel disease or its subtypes.

## Contribution

The study uses Mendelian randomization to show no causal link between glucose and IBD, challenging prior observational findings.

## Key findings

- No causal effect of genetically predicted glucose on IBD was found.
- IBD subtypes Crohn’s disease and ulcerative colitis also showed no causal link to glucose.
- No evidence of IBD or its subtypes affecting glucose or glycemic traits.

## Abstract

Association between glucose and inflammatory bowel disease (IBD) was found in previous observational studies and in cohort studies. However, it is not clear whether these associations reflect causality. Thus, this study investigated whether there is such a causal relation between elevated glucose and IBD, Crohn’s disease (CD) and ulcerative colitis (UC).

We performed a two-sample Mendelian Randomization (MR) with the independent genetic instruments identified from the largest available genome-wide association study (GWAS) for IBD (5,673 cases; 213,119 controls) and its main subtypes, CD and UC. Summarized data for glucose which included 200,622 cases and glycemic traits including HbA1c and type 2 diabetes(T2DM) were obtained from different GWAS studies. Primary and secondary analyses were conducted by preferentially using the radial inverse-variance weighted (IVW) approach. A number of other meta-analysis approach and sensitivity analyses were carried out to assess the robustness of the results.

We did not find a causal effect of genetically predicted glucose on IBD as a whole (OR 0.858; 95% CI 0.649–1.135; P = 0.286). In subtype analyses glucose was also suggestively not associated with Crohn’s disease (OR 0.22; 95% CI 0.04-1.00; P = 0.05) and ulcerative colitis (OR 0.940; 95% CI 0.628–1.407; P = 0.762). In the other direction, IBD and its subtypes were not related to glucose and glycemic traits.

This MR study is not providing any evidence for a causal relationship between genetically predicted elevated glucose and IBD as well as it’s subtypes UC and CD. Regarding the other direction, no causal associations could be found. Future studies with robust genetic instruments are needed to confirm this conclusion.

The online version contains supplementary material available at 10.1186/s12920-024-01923-6.