Abstract MP91: History of Infertility and Risk of Type 2 Diabetes Mellitus in Women

Background: Increasing evidence supports a biologically plausible association between delayed conception and metabolic dysfunction, including insulin resistance and inflammation; however, few studies have assessed whether infertility is associated with metabolic diseases such as type 2 diabetes (T2D) later in life. Objective: We prospectively evaluated the association between a history of infertility and T2D risk in a large cohort of women. Methods: Participants of the Nurses’ Health Study II self-reported their infertility status (>12 months attempting a pregnancy), lifestyle characteristics, and several health-related outcomes, via biennial questionnaires (1989-2011). Those reporting infertility were asked to cite the clinical reason(s), if known. Exposure status was updated every two years and carried forward to represent “ever”. Cox proportional hazards models estimated the relative risk (HR) and 95% confidence interval (CI) comparing participants with a history of infertility versus none. Multivariable models adjusted for age, body mass index (BMI), physical activity, healthful dietary pattern score, smoking, alcohol consumption, and several other lifestyle factors. Results: Participants (N=115,750) were on average 35 years old (range 25-44) with a BMI of 24.1 (SD=5.0) at baseline, with 91.7% Caucasian. Twenty-one percent (n=24,118) reported a history of infertility at baseline or follow-up. Incident T2D was reported in 5,414 participants during follow-up (2.6 cases/1,000 person-years). Women with a history of infertility had a significant 21% greater risk of T2D compared to women without infertility after adjusting for several T2D risk factors (multivariable HR=1.21, CI=1.14, 1.29). Infertility due to ovulation disorders was associated with a 47% greater risk of T2D (HR=1.47, CI=1.33, 1.64), and tubal blockage with a 32% greater risk (HR=1.32, CI=1.09, 1.61), compared to no infertility. Other reasons for infertility were not associated with T2D risk, including cervical mucus disorder (HR=1.09, CI=0.80, 1.48), male factor (HR=1.13, CI=0.96, 1.32), and “other” (HR=1.08, CI=0.90, 1.28). Tests for interaction did not indicate significant effect modification across BMI categories for total infertility (BMI<25: HR=1.34, CI=1.03, 1.74; BMI 25-29: HR=1.38, CI=1.18, 1.60; BMI 30+: HR=1.15, CI=1.07, 1.34; p-interaction=0.13). Effect modification by BMI category was suggested for infertility due to ovulation disorders (BMI<25: HR=2.14, CI=1.58, 3.67; BMI 25-29: HR=1.43, CI=1.08, 1.89; BMI 30+: HR=1.35, CI=1.20, 1.52; p-interaction=0.06). Conclusions: Among women, a history of infertility is significantly associated with T2D later in life, specifically infertility due to ovulation disorders and tubal blockage.