Abstract
AIMS/HYPOTHESIS: We sought to evaluate the relationship between delayed conception and type 2 diabetes risk, given that there are plausible underlying mechanisms linking the two, including inflammation and insulin resistance. METHODS: Participants of the Nurses' Health Study II prospective cohort were included if they were free of chronic disease (cardiovascular disease, type 2 diabetes, cancer) at baseline. Biennial questionnaires updated information on infertility status (>12 months attempted pregnancy), lifestyle characteristics and several health-related outcomes. Self-reported cases of diabetes were confirmed using a follow-up questionnaire. Multivariable Cox proportional hazards models were used to compute the HRs and 95% CIs. RESULTS: Incident type 2 diabetes occurred in 5,993 of the 112,106 participants over 24 years of follow-up (1989-2013). A history of infertility was reported in 27,774 (24.8%) women and was associated with a 20% greater risk of developing diabetes, compared with those never reporting infertility (HR 1.20 [95% CI 1.14, 1.28]), after adjusting for age, lifestyle factors, marital status, oral contraceptive use, family history of diabetes and BMI. Compared with women without a history of infertility, the causes of infertility associated with a higher diabetes risk were ovulation disorders (HR 1.43 [95% CI 1.29, 1.58]) and tubal factor (HR 1.34 [95% CI 1.13, 1.58]). Cervical factor (HR 1.06 [95% CI 0.81, 1.40]) and endometriosis (HR 1.06 [95% CI 0.89, 1.27]) were not associated, while male factor infertility was associated with a modestly higher diabetes risk (HR 1.15 [95% CI 1.00, 1.33]). CONCLUSIONS/INTERPRETATION: These novel findings suggest a history of infertility, particularly that related to ovulation disorders and tubal blockage, is significantly associated with a higher risk of type 2 diabetes.