Associations between fetal sex and the development of gestational diabetes mellitus (GDM) in twin pregnancies

Twin pregnancy is increasing worldwide, and one perinatal outcome increased with multiple gestations is GDM. Recent studies have suggested that in singleton pregnancies, fetal sex may affect insulin sensitivity, but the effects of fetal sex in twins and the development of GDM is unknown. We hypothesized that rates of GDM and degree of insulin resistance may vary in twin pregnancies based on the fetal sex pairing: male-male (M-M), male-female (M-F), or female-female (F-F). Our objective was to employ a large population-based database to ascertain any correlations between fetal sex and GDM in multifetal gestations. A 2-hospital, single academic institution database comprised of over 60,000 participants with pregnancy data from Aug. 2011 to Jan. 2022 was employed. All twin deliveries of live-born neonates > 24 weeks gestational age from gravidae without pre-existing diabetes were included. These entries were then grouped based on the fetal sex of the pairing: M-M, M-F, or F-F. The presence or absence of gestational diabetes and type of gestational diabetes—diet-controlled (A1DM) vs medication-controlled (A2DM)— were identified. Statistical analysis was performed using a generalized linear mixed method. A p value of < 0.05 was considered statistically significant. We identified 1939 twin deliveries that met the inclusion criteria in our database (M:M=666, M:F=629, and F:F=644). We found no association between fetal sex pairing and the development of GDM (p=0.32) (Table 1). There was a significant association between the fetal sex pairing and the type of GDM developed (p=0.04), with 30.77% of M-M twins, 32.08% M-F twins, and 59.46% of the F-F twins classified as A2DM. While GDM is of multifactorial origin, we found a significant association between the fetal sex pairing and the treatment needed for gravidae with twins who develop GDM. A higher proportion of deliveries of F:F twins was associated with A2DM when compared M:F or M:M deliveries. Further research on the physiology driving this association is warranted.