Background/Objectives: Inflammation may play a critical role in the pathogenesis of gestational diabetes mellitus (GDM). However, evidence linking early-pregnancy cytokines to subsequent GDM risk remains inconsistent, with most prior research focusing only on CRP, IL6, and TNFα. In this study, we expand on prior work by evaluating a broader range of immune markers and assessing sociodemographic factors as potential moderators. Methods: Data from a prospective U.S. pregnancy cohort (n = 308) were analyzed. Twenty cytokines were quantified in maternal first-trimester plasma using the MILLIPLEX High-Sensitivity Human Cytokine Magnetic Bead Panel. One-hour oral glucose (50 g) tolerance test (OGTT) values assessed at an average gestational age of 27.7 weeks (SD = 2.9) and GDM diagnosis were abstracted from medical records. Multivariable linear and logistic regression models were used to examine associations between cytokines and 1 h 50 g OGTT levels or GDM diagnosis, adjusting for key sociodemographic factors. Interactions terms were included to evaluate whether sociodemographic factors moderated cytokine–GDM relationships. Results: Sixteen women (5.1%) were diagnosed with GDM. Higher first-trimester high-sensitivity-IL6 levels were significantly associated with increased 1 h 50 g OGTT values (b = 3.76; 95% CI: 0.21, 7.32; p = 0.04) and greater odds of GDM (OR = 2.36; 95% CI: 1.17, 4.77; p = 0.02). These associations were more pronounced among Non-Hispanic White women compared to Non-Hispanic Black women (p for interaction = 0.03) and potentially those with normal weight or underweight during early pregnancy compared to overweight or obese women (p for interaction = 0.08). Conclusions: Elevated inflammatory markers, particularly high-sensitivity IL6, in early pregnancy are linked to impaired glucose metabolism and increased GDM risk later in pregnancy. These relationships appeared stronger in Non-Hispanic White women and women with normal weight or underweight during early pregnancy, underscoring the potential to develop serology-based early identification and prevention strategies.
Meng et al. (Tue,) studied this question.