Circulating fatty acids and gestational diabetes mellitus: A systematic review and meta-analysis of observational studies

Abstract

Background: Gestational diabetes mellitus (GDM) is a prevalent pregnancy complication. Altered fatty acid (FA) metabolism may contribute to GDM development, yet evidence regarding specific circulating FAs remains inconclusive. Objective: This systematic review and meta-analysis compared circulating FA profiles between pregnant women with and without GDM and examined their associations with GDM risk. Methods: We searched PubMed, Scopus, and Web of Science for observational studies reported circulating FAs in relation to GDM risk. Pooled standardized mean differences (SMDs) and odds ratios (ORs) were calculated using random-effects models. Subgroup analyses explored heterogeneity sources, and the Newcastle-Ottawa Scale assessed risk of bias (RoB). Results: Forty-four studies were included. Meta-analysis of ORs indicated that per one-SD increase, C16:0 was associated with higher GDM odds (OR: 1.20, 95CI: 1.04, 1.38). Conversely, very-long-chain saturated FAs (C22:0 and C24:0), specific omega-6 FAs (C18:2, C20:2, and C22:4) were associated with lower odds. SMD analysis revealed significantly lower circulating levels of C22:0, C15:0, and C17:0 in women with GDM. Subgroup analyses identified FA form (e.g., free FAs vs. phospholipids) as a significant heterogeneity source for eight FAs, measurement unit (absolute concentration vs. relative percentage) for three FAs, while RoB, study design, and trimester were sources for limited specific FAs. Conclusions: GDM is associated with distinct circulating FAs patterns. C16:0 is associated with higher odds of GDM, whereas linoleic acid, very-long-chain Saturated FAs, and selected omega-6 FAs were related to lower odds. Prospero registration code: CRD42025649380.