Assessment of glycemic susceptibility across multiple urological and reproductive disorders

To test the glycemic susceptibility in three urological cancers and eight urological/reproductive diseases using the Mendelian randomization (MR) method.

Two-sample MR was applied to investigate the causal role of three glycemic traits (type II diabetes, fasting glucose and glycated hemoglobin (HbA1c)) in eleven urological/reproductive diseases (kidney cancer, bladder cancer, prostate cancer, kidney/ureter stone, urinary incontinence, benign prostatic hyperplasia, erectile dysfunction, female infertility, male infertility, abnormal spermatozoa and polycystic ovary syndrome). Further multivariate MR (MVMR) and mediating analysis were performed to investigate the associations.

Among all the 11 diseases, type II diabetes was positively associated with erectile dysfunction, which was stable across both cohorts [odds ratio (OR): 1.59, 95% confidence interval (CI): 1.15-2.20, P = 0.005 for FinnGen Biobank and OR: 1.14, 95% CI: 1.08-1.21, P < 0.001 for the other cohort]. Also, type II diabetes was negatively associated with male infertility (OR: 0.57, 95% CI: 0.39-0.84, P = 0.005). In addition, all three glycemic traits were observed to be positively associated with polycystic ovary syndrome (OR: 2.36, 95% CI: 1.16-4.76, P = 0.017 for fasting glucose per mmol/L; OR: 3.04, 95% CI: 1.10-8.39, P = 0.032 for HbA1c per percentage; and OR: 1.21, 95% CI: 1.00-1.46, P = 0.046 for type II diabetes). Mediating analysis confirmed the effect of type II diabetes on these diseases.

There existed glycemic susceptibility in erectile dysfunction, male infertility and polycystic ovary syndrome. We could not conclude stable glycemic susceptibility in other urological/reproductive diseases.