Abstract P324: Female Reproductive Factors and Risk of Type 2 Diabetes and Cardiovascular Disease Among Women With a History of Gestational Diabetes

Introduction: The link between gestational diabetes mellitus (GDM) and long-term risk of type 2 diabetes (T2D) and cardiovascular disease (CVD) is well established; however, risk factors underlying the progression of disease remain uncertain. Hypothesis: Female reproductive factors including ages at menarche, menopause, and first birth, number of live births, and surgically-induced menopause (uni- or bilateral oophorectomy or hysterectomy) are associated with higher risk of progression, while breastfeeding is associated with lower risk of progression from GDM to T2D/CVD. Methods: Participants in the Nurses’ Health Study II reported reproductive history at cohort baseline and over follow-up, including 5346 women with a history of GDM. Self-reported incident T2D or CVD (myocardial infarction, coronary revascularization or stroke) were confirmed via questionnaire or medical records. We estimated the hazard ratios (HR [95%]) across quintiles of each reproductive factor with incident T2D and CVD using Cox models adjusting for age, race/ethnicity, smoking, BMI at 18 years, physical activity, family history of T2D or CVD, alcohol intake, menopausal status, aspirin use, and Alternate Healthy Eating Index. Results: We documented 988 incident T2D and 149 CVD cases over 25 years of follow-up. In adjusted models, higher total lactation duration was associated with lower risk of T2D (5 categories: 0, 1-6, 7-12, 13-24, >24 months, p for trend=0.01; highest vs. lowest category: HR 0.77 [95%CI: 0.60, 0.98]) and CVD (p for trend=0.03, HR 0.39 [95%CI: 0.19, 0.80]). Early age at menarche was linearly associated with higher risk of T2D (5 categories: ≤11, 12, 13, 14, >14 y: p for trend <0.0001), lowest (≤11 y) vs. reference (13 y) category: HR 1.28 [95%CI: 1.06, 1.53], while no trend could be observed for CVD outcomes (p for trend=0.48). Higher age at 1 st birth was associated with lower CVD risk (5 categories: <23, 23-25 [reference], 26-29, 30-34, ≥35 y, p for trend=0.001; highest vs reference category: HR 0.17 [95%CI: 0.05, 0.57]), but not T2D). Compared with natural menopause, surgically induced menopause was associated with higher T2D risk: 1.32 (1.00, 1.73). Number of live births and age at menopause were not associated with T2D or CVD among women with GDM history. Conclusions: Breastfeeding was associated with lower T2D and CVD risks among women with GDM history, suggesting some shared risk factors or etiologies across reproductive lifespan and long-term cardiometabolic health. Ages at menarche and 1 st birth showed differential associations with T2D and CVD.