Glucoregulatory and Inflammatory Trajectories in Pregnancy with Obesity: Secondary Analysis of a Randomized Exercise Trial

Objective

To evaluate moderate-intensity exercise effects on glucoregulatory and inflammatory markers in pregnant women with obesity.

Methods

Secondary analysis of the Expecting Study ( NCT02125149 ) included 263 sedentary pregnant women with pre-pregnancy BMI ≥30kg/m ² randomized to exercise (EX, n=157) or standard-of-care (SoC, n=106). Fasting biomarkers were assessed at 12.14±0.50, 24.19±0.68, and 36.03±0.58 weeks’ gestation. Linear mixed-effects models evaluated intervention and gestational effects at 24-36 weeks. Exploratory repeated-measures continuous glucose monitoring (CGM) included 18 participants (SoC=6, EX=12), evaluating 24-h/temporal glycemia and exploring inflammatory marker associations.

Results

Insulin, C-peptide, HOMA2-IR, HOMA2-%B , IL-6, and TNF-α increased with gestation, while HOMA2-%S and CRP decreased (all p<0.001). Exercise did not affect fasting glucose or inflammatory markers. CGM-wear yielded 12-15 days/trimester with >95% valid wear time; glycemia remained normoglycemic. By 36-weeks, SoC-metrics declined in 24-h and nocturnal glucose and time-in-range (TIR), with increased time-below-range (all p<0.022). TIR was inversely associated with IL-6 at 24-weeks (−0.23 [95%CI: −0.43,-0.02] p=0.035), and mean amplitude of glycemic excursion positively with TNF-α at 36-weeks (0.02 [95%CI: 0.00,0.04] p=0.033).

Conclusion

Exercise did not modify mid-to late-gestation fasting glucoregulatory or inflammatory profiles. High CGM-adherence and preliminary indications of distinct longitudinal glycemic patterns support further CGM evaluation in antepartum behavioral interventions.

What is already known about this subject?

• Pregnancy and obesity increase insulin resistance and metabolic stress; exercise may improve maternal metabolic health.

• Continuous Glucose Monitoring (CGM) can detect glycemic patterns not captured by fasting measures but is understudied in pregnancies with obesity without diabetes.

What are the new findings in your manuscript?

• Exercise did not alter fasting glucoregulatory or inflammatory trajectories despite substantial gestational metabolic adaptation.

• Exploratory CGM showed declining late-gestation glycemic metrics in the standard of care group, whereas these metrics remained stable in the exercise group.

How might your results change the direction of research or the focus of clinical practice?

• Fasting biomarkers alone may not capture metabolic responses to antepartum exercise.

• Larger trials should evaluate CGM-derived glycemic patterns and clinically meaningful targets in pregnancies with obesity.