The causality between physical activity and gestational diabetes mellitus: a Mendelian randomization study

Area of Science:

• Genetics
• Epidemiology
• Metabolic Health

Background:

• Observational studies link physical activity and sedentary behavior to gestational diabetes mellitus (GDM), lipids, and body mass index (BMI).
• The causal direction and mediating mechanisms remain unclear, hindering precise prevention strategies for GDM.

Purpose of the Study:

• To investigate the causal relationship between GDM, physical activity, and sedentary behavior using Mendelian randomization (MR).
• To quantify the mediating roles of BMI and lipids in the association between lifestyle factors and GDM risk.

Main Methods:

• Bidirectional dual-sample Mendelian randomization (MR) analysis using genome-wide association study data.
• Mediation analysis to assess the indirect effects of physical activity and screen time on GDM risk via BMI and lipid profiles.

Main Results:

• Increased physical activity time causally reduced GDM risk (OR=0.977), primarily mediated by BMI (53.6%).
• Increased leisure screen time causally increased GDM risk (OR=1.125), mediated by BMI (81.8%), HDL-C (11.2%), and ApoA1 (10.1%).
• BMI played a major, almost complete mediating role in the physical activity-GDM pathway, and a significant role in the screen time-GDM pathway.

Conclusions:

• Physical activity indirectly lowers GDM risk by reducing BMI.
• Excessive leisure screen time increases GDM risk by negatively impacting BMI, HDL-C, and ApoA1.
• Prioritizing weight control and integrating physical activity with reduced sedentary behavior are crucial for GDM prevention through optimized metabolic health.