Inflammatory Biomarkers in Relation to Gestational Diabetes Mellitus: A Prospective Study and Meta-Analysis

The prospective association between C-reactive protein (CRP) and gestational diabetes mellitus (GDM) is inconsistent, and the independent association of tumor necrosis factor-α (TNF-α) with GDM risk remains unclear. We aimed to prospectively evaluate associations of early-pregnancy CRP and TNF-α with incident GDM and updated the evidence through a meta-analysis.

Serum CRP and TNF-α levels were measured at 6-15 weeks of gestation among 332 GDM and 664 matched controls. Conditional logistic regression was used to compute odds ratios (ORs) and 95% confidence intervals (CIs). PubMed and EMBASE were searched up to June 18, 2025, to identify prospective studies that investigated associations of CRP and TNF-α levels with GDM.

After multivariable adjustment, OR for GDM was 1.75 (95% CI 1.07, 2.84) for the extreme-quartile comparison of CRP and a non-linear association was noted (P-nonlinear = 0.03). TNF-α was associated with a 1.82-fold (95% CI 1.07, 3.09; P-trend = 0.04) higher risk of GDM. CRP and TNF-α levels were positively associated with the risk of GDM, independent of each other and of pre-pregnancy body mass index (BMI). The meta-analysis confirmed the positive association between CRP and GDM risk, independent of BMI. CRP levels were associated with adverse metabolic traits (e.g. fasting insulin, homeostasis model assessment for insulin resistance [HOMA-IR], and HOMA-β), while TNF-α was not.

Elevated CRP and TNF-α levels in early pregnancy were independently associated with increased risks of GDM. While our findings support potential roles of inflammation in GDM, specific pathways involved should be examined to identify novel targets for the prevention of GDM.