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

Objective 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 the potential cause of the sex-specific association. Methods The study was a prospective analysis based on the UK biobank (UKB) data. We included 359 503 participants, all of whom were without T2D 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 multi-adjusted models. Results 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 multi-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 ( P _interaction =0.008), 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 ( P _interaction =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). Furthermore, we observed that the elevated risk of T2D associated with IBS may be strengthened by the genetic susceptibility to T2D. Conclusions A sex-specific association between IBS and T2D was found, and SHBG level might be the cause of the sex-specific association.