Is fetal sex associated with maternal diabetes 10-14 years after delivery?

OBJECTIVE: We examined the association between fetal sex and the risk of maternal prediabetes or diabetes 10-14 years after delivery. Secondarily, we assessed whether this association varied by GDM status and whether measures of maternal insulin sensitivity and resistance varied by fetal sex. MATERIALS AND METHODS: This is a secondary analysis from the prospective, international Hyperglycemia and Adverse Pregnancy Outcome Follow-Up Study (HAPO FUS). The exposure was assigned fetal sex at birth (female as the reference). The primary outcome was prediabetes or diabetes assessed 10-14 years after the index pregnancy. The effect modifier was GDM per the International Association of Diabetes and Pregnancy Study Group criteria. Modified Poisson regression models were used and adjusted for baseline covariates at enrollment and time from enrollment to follow-up. We secondarily assessed whether the association between fetal sex and prediabetes or diabetes varied by GDM and whether maternal insulin sensitivity at pregnancy enrollment and insulin resistance at 10-14 year follow-up differed by fetal sex. RESULTS: Of 4,609 individuals in the analytic sample, 48.9% of infants were assigned female sex at birth, which was 47.1% with GDM and 49.2% without GDM (p=0.3). At a median 11.6 years after delivery, 22.4% postpartum individuals developed prediabetes and 2.9% developed diabetes. The risk of prediabetes or diabetes did not differ by fetal sex (female vs. male: 24.7 vs. 24.6%; adjusted risk ratio, aRR: 1.00, 95% CI: 0.89, 1.12). This association was similar regardless of GDM status (interaction p=0.6). There was no association between fetal sex and insulin sensitivity at enrollment or insulin resistance at follow-up. DISCUSSION: In the prospective HAPO FUS cohort, there was no association between fetal sex and the risk of maternal prediabetes or diabetes 10-14 years after delivery. Further research is needed to better understand the possible impact of fetal sex on peripartum glucose homeostasis.