Introduction and Objective: Long-term impacts of gestational diabetes mellitus (GDM) on host metabolism are unknown. We aimed to identify serum metabolites linking history of GDM to type 2 diabetes (T2D).Methods: Among 2968 parous women in the Hispanic Community Health Study/Study of Latinos, we performed a metabolome-wide association analysis to identify metabolites associated with history of GDM; constructed GDM-related metabolite modules using network analysis; created a GDM-related metabolite score using elastic net regression; and linked these metabolite signatures with incident T2D over 12 years.Results: Ninety-six metabolites differed for women with and without history of GDM, 94 of which clustered into 5 modules. Amino acid (AA) module (mostly branched-chain and aromatic AA derivatives) and phosphatidylethanolamine module were positively associated with history GDM and T2D risk, while glycerophospholipid, acyl choline, and sphingomyelin modules were inversely associated with history of GDM and T2D risk (Fig A). The GDM-related metabolite score (Fig B) was associated with higher risk of T2D (HR = 1.37 [95% CI: 1.23-1.54] per SD, Fig C). AA module and the metabolite score partially mediated the association between history of GDM and T2D (29% and 30%).Conclusion: Circulating metabolites may play a role in GDM-related T2D risk in US Hispanic/Latino women.
Y. Wang: None. C.R. Isasi: None. A. Stuebe: Other Relationship; Couplet Care. M.L. Daviglus: None. E. Boerwinkle: None. R. Burk: None. R. Kaplan: None. Q. Qi: None. B. Peters: None.
American Diabetes Association (11-23-PDF-60)
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