High Serum Polyunsaturated Fatty Acids for the Increased Risk of Gestational Diabetes Mellitus Through LPC Pathways: A Prospective Nested Case–Control Study in China

Abstract

Aims The study aimed to investigate the following: (1) whether early‐pregnancy serum polyunsaturated fatty acid (PUFA) species are associated with the risk of gestational diabetes mellitus (GDM); and (2) whether lysophosphatidylcholine (LPC)18:0 may statistically explain these associations in Chinese pregnant women. Materials and Methods We conducted a 1:1 age‐matched case–control study of 486 pregnant women nested within a prospective cohort in Tianjin, China. Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression analysis was used to identify the PUFA species independently associated with GDM. Conditional logistic regression was conducted to obtain odds ratios (ORs) and their 95% confidence intervals (CIs). Sobel mediation analysis was used to assess the potential statistical role of LPC18:0. Results Among five PUFA species that differed significantly between cases and controls, arachidonic acid (AA, 20:4) and docosahexaenoic acid (DHA, 22:6) were selected and further analyzed. High AA (≥ 3.63 nmol/mL) and DHA (≥ 0.59 nmol/mL) were associated with increased GDM risk, with multivariable‐adjusted ORs of 2.89 (95% CI: 1.84–4.54) and 2.90 (95% CI: 1.82–4.63), respectively. These associations were stronger among women with pre‐pregnancy overweight/obesity (AA, OR: 5.32, 95% CI: 2.48–11.42; DHA, OR: 3.39, 95% CI: 1.65–6.99). Further adjustment for high LPC18:0 substantially attenuated the associations of AA (OR: 0.90, 95% CI: 0.45–1.80) and DHA (OR: 0.97, 95% CI: 0.51–1.85) with GDM risk, with Sobel test p values < 0.0001. Conclusions Higher serum AA and DHA levels in early pregnancy were associated with increased GDM risk. LPC18:0 may statistically explain part of these observed associations.