Associations of mid-pregnancy plasma fatty acid patterns with gestational diabetes mellitus risk: A 1:2 matched case-control study.

Background

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Aims

Gestational diabetes mellitus (GDM) is a common metabolic complication of pregnancy, closely related to insulin resistance and altered fatty acid metabolism. However, evidence on mid-pregnancy fatty acid profiles and GDM risk remains limited and inconsistent. We comprehensively characterized mid-pregnancy circulating fatty acid profiles and their derived patterns in relation to GDM risk in a matched case-control study.

Methods

Based on a prospective cohort study conducted in Shenzhen, China, we performed a 1:2 matched case-control study including 290 GDM cases and 580 normal glucose tolerance controls, matched by maternal age and pre-pregnancy BMI. Conditional logistic regression was used to examine associations between individual fatty acids and GDM risk. Multivariable linear regression with cluster-robust standard errors was applied to assess associations with oral glucose tolerance test glucose levels. Principal component analysis was further used to identify fatty acid patterns.

Results

Medium-chain saturated fatty acids, including C12:0 and C14:0, were inversely associated with GDM risk and post-load glucose levels. The highest quartile of C12:0 was associated with a 48% lower GDM risk. Total odd-chain fatty acids also showed a protective association. In contrast, very-long-chain saturated fatty acids, particularly C22:0 and C24:0, were positively associated with GDM risk and post-load glucose, with the highest quartile of C22:0 associated with a more than two-fold higher risk. Among polyunsaturated fatty acids, ALA was associated with lower GDM risk, whereas DHA was associated with higher risk. Principal component analysis identified a fatty acid pattern characterized by higher C24:0, C22:0, and C18:1n-9 and lower C18:3n-3, C17:0, and C18:2n-6, which was associated with increased GDM risk and elevated post-load glucose.

Conclusion

Mid-pregnancy circulating fatty acid profiles were associated with GDM risk and glycemic levels. Fatty acid pattern analysis provides a complementary perspective to individual fatty acid associations, offering an integrated view of fatty acid metabolism in pregnancy.