Introduction: With the implementation of the universal two-child policy, the number of pregnant women of advanced maternal age (AMA) will increase steadily. We aimed to investigate whether the effect of gestational weight gain on insulin resistance (IR) before delivery was mediated by serum adipokine concentrations in AMA.

Material and methods: This cross-sectional study included 80 pregnant women of AMA recruited consecutively before delivery from the Department of Obstetrics and Gynecology between August 2016 and July 2017. At delivery, maternal weight during the third trimester was recorded and serum adipokines were measured. IR was calculated using the homeostasis model assessment 2 (HOMA2) method.

Results: Weight gain (WG) during the third trimester was positively associated with serum leptin concentrations (r = 0.34, p = 0.0018) and HOMA-IR indices (r = 0.25, p = 0.025), but not related with serum concentration of adiponectin (r = 0.12, p = 0.28). WG during the third trimester and serum concentration of leptin were independently associated with the level of HOMA-IR by multivariate analysis. Subsequently, according to mediation analysis, the association between WG during the third trimester and HOMA-IR mediated by serum leptin concentrations was statistically significant (z = 1.588, p < 0.05).

Conclusions: Taken together, our findings suggest that the relationship between WG during the third trimester and IR was mediated by serum leptin concentrations in AMA, but not serum adiponectin concentrations.