Gallstone Disease and Type 2 Diabetes Risk: A Mendelian Randomization Study

The presence of gallstone disease (GSD) was reported to be positively associated with diabetes risk. Whether the association is causal remains unclear. We aim to examine the potential causal association between GSD and type 2 diabetes risk using a Mendelian randomization analysis. Observational study was conducted among 16,299 participants who were free of cancer, heart disease, stroke, and diabetes at baseline in the Dongfeng-Tongji cohort study. GSD was diagnosed by experienced physicians by abdominal B-type ultrasound inspection and type 2 diabetes was defined according to the criteria of the American Diabetes Association. Cox proportional hazard regression model was used to examine the association of GSD with type 2 diabetes risk. A genetic risk score (GRS) for GSD was constructed with eight single nucleotide polymorphisms that were derived from the previous genome-wide association studies. The causal associations of the score for GSD with type 2 diabetes were tested among 7,000 participants in Mendelian randomization analysis. We documented 1,110 incident type 2 diabetes cases during 73,895 person-years of follow-up from 2008 to 2013 (median 4.6 years). Compared with participants without GSD, the multivariate-adjusted hazard ratio of type 2 diabetes risk in those with GSD was 1.22 (95% confidence interval [CI], 1.03-1.45, P = 0.02). Each 1 SD (0.23) increment in the weighted GRS was associated with a 17% increment of type 2 diabetes risk (odds ratio = 1.17, 95% CI, 0.90-1.52) without statistical significance (P = 0.25). Conclusion: The present study supported a positive but not a causal association of GSD with type 2 diabetes risk. More studies are needed to verify our findings.