Differential Impact of Early Versus Mid‐Pregnancy Physical Activity on Gestational Diabetes Mellitus: The Mediation Effect of Blood Lipid Profiles

ABSTRACT Aims Emerging evidence links low physical activity (PA) and dysregulated lipid metabolism to gestational diabetes mellitus (GDM) risk. This study aimed to determine which gestational stage is more vulnerable to low PA and whether changes in blood lipids mediate this risk. Materials and Methods A retrospective analysis was conducted among 3997 pregnant women (614 with GDM) during the COVID‐19 lockdown in Shanghai, a unique natural experiment provided by the uniform imposition of PA restrictions. Multivariable logistic regression estimated the association between low PA at different gestational stages and GDM risk, while mediation analyses explored the role of blood lipids. Results Women with GDM were older and had higher rates of overweight/obesity compared with non‐GDM participants. Notably, the GDM group exhibited a higher prevalence of low PA during early pregnancy and elevated lipid levels. Logistic regression demonstrated that low PA during early pregnancy was significantly associated with increased GDM risk (OR = 2.041, 95% CI: 1.577–2.644). Moreover, low PA was significantly linked to dysregulated lipid profiles in both early and mid‐pregnancy. Mediation analysis further indicated that elevated total cholesterol (TC) levels partially mediated this relationship. In contrast, low PA in mid‐pregnancy was not directly linked to GDM (OR = 1.244, 95% CI: 0.966–1.6), although increased triglyceride (TG) levels during this stage mediated an effect on GDM risk. Conclusions Early pregnancy is a critical window for GDM prevention. Additionally, these findings advocate for stage‐specific exercise and lipid management strategies to reduce GDM risk and improve maternal and neonatal outcomes.