Roles of obesity in mediating the causal effect of attention-deficit/hyperactivity disorder on diabetes

Previous observational studies have reported potential associations among attention-deficit/hyperactivity disorder (ADHD), obesity, and diabetes (including type 1 and type 2 diabetes mellitus [T1DM/T2DM]). However, whether the association between ADHD and diabetes is mediated by obesity is unknown. With two-sample Mendelian randomization, we analysed the causal effect of ADHD on T1DM and T2DM and six obesity-related traits [including body mass index, waist circumference (WC), hip circumference, waist-to-hip ratio (WHR), body fat percentage and basal metabolic rate] and the causal effect of these obesity-related traits on T1DM/T2DM. Finally, with multivariable Mendelian randomization, we explored and quantified the possible mediation effects of obesity-related traits on the causal effect of ADHD on T1DM/T2DM. Our results showed that ADHD increased the risk of T2DM by 14% [odds ratio (OR) = 1.140, 95% confidence interval (CI) = 1.005-1.293] but with no evidence of an effect on T1DM (OR = 0.916, 95% CI = 0.735-1.141, = 0.433.). In addition, ADHD had a 6.1% increased causal effect on high WC (OR = 1.061, 95% CI = 1.024-1.099, = 0.001) and an 8.2% increased causal effect on high WHR (OR = 1.082, 95% CI = 1.035-1.131, = 0.001). In addition, a causal effect of genetically predicted high WC (OR = 1.870, 95% CI = 1.594-2.192,