Sex hormone-binding globulin and sex-specific association between irritable bowel syndrome and type 2 diabetes: a prospective cohort study

To investigate the sex-specific association between irritable bowel syndrome (IBS) and type 2 diabetes (T2D), and further explore whether sex-hormone binding globulin (SHBG) was an associated factor of the sex-specific association. The study was a prospective analysis based on the UK biobank (UKB) data. We included 359 503 participants, all of whom were without diabetes diagnosis and had complete SHBG information at baseline. Hazard ratio (HR) and 95% confidence interval (CI) were calculated using non-IBS group as the reference, further stratified by sex and SHBG levels in multivariable-adjusted models, including demographics, lifestyle factors, and disease history. During a median follow-up of 10.4 years, 14 317 incident T2D cases had been documented. A statistically significant increased risk of T2D with IBS compared to those without IBS was observed in all multivariable-adjusted models (HR = 1.32, 95% CI = 1.23–1.42, P < 0.001). Additionally, a sex-specific association between IBS and T2D was found (Pinteraction = 0.004), with the risk in women (HR = 1.43, 95% CI = 1.31–1.57) being higher than in men (HR = 1.14, 95% CI = 1.01–1.29). A significant effect modification of SHBG was also observed in the association between IBS and T2D (Pinteraction = 0.001). The risk of incident T2D was higher in participants with higher SHBG levels (HR = 1.42, 95% CI = 1.25–1.63) than in those with lower SHBG levels (HR = 1.26, 95% CI = 1.16–1.37). A sex-specific association between prevalent IBS and T2D incidence was found, and SHBG level might modify the association.