Reproductive factors, genetic susceptibility and risk of type 2 diabetes: A prospective cohort study

Aim: To explore the relationships of multiple reproductive factors with type 2 diabetes mellitus (T2DM) risk and the joint effects of reproductive factors and genetic susceptibility. Methods: We included 262,368 women without prevalent T2DM from the UK biobank. Cox proportional hazards regression models were employed to estimate the relationships of reproductive factors with T2DM risk and the joint effects of reproductive factors and genetic susceptibility. Results: During a mean follow-up of 12.2 years, 8,996 T2DM cases were identified. Early menarche ( <12 years, hazard ratio (HR) 1.08 [95 % confidence interval (CI) 1.02;1.13]), late menarche ( >= 15 years, HR 1.11 [1.04;1.17]), early menopause ( <45 years, HR 1.20 [1.12;1.29]), short reproductive lifespan ( <30 years, HR 1.25 [1.16;1.35]), hysterectomy (1.31, HR [1.23;1.40]), oophorectomy (HR 1.28 [1.20;1.36]), high parity ( >= 4, HR 1.25 [1.17;1.34]), early age at first live birth ( <20 years, HR 1.23 [1.16;1.31]), miscarriage (HR 1.13 [1.07;1.19]), stillbirth (HR 1.14 [1.03;1.27]), and ever used hormonal replacement therapy (HR 1.19 [1.14;1.24]) were related to a higher T2DM risk, while ever used oral contraceptives (HR 0.93 [0.89;0.98]) was related to a lower T2DM risk. Furthermore, women with reproductive risk factors and high genetic risk had the highest T2DM risk compared to those with low genetic risk and without reproductive risk factors. Conclusion: Our findings show that multiple reproductive factors are related to T2DM risk, particularly in women with high genetic risk.