Gestational Diabetes Mellitus, Postpartum Lipidomic Signatures, and Subsequent Risk of Type 2 Diabetes: A Lipidome-Wide Association Study

<p><em><strong>OBJECTIVE</strong></em> To identify a postpartum lipidomic signature associated with gestational diabetes (GDM) and investigate the role of the identified lipids in the progression to type 2 diabetes (T2D).</p> <p><em><strong>RESEARCH DESIGN AND METHODS</strong></em> This was a prospective cohort study of 1409 women who were enrolled at 24-72 hours after delivery of a singleton baby and followed prospectively at the Boston Medical Center, Boston, MA. Lipidome was profiled by liquid chromatography–tandem mass spectrometry platform. Diagnoses of GDM and incident T2D were extracted from medical records and verified using plasma glucose levels. </p> <p><em><strong>RESULTS</strong></em> Mean (SD) age of study women at baseline was 28.5±6.6 years. 219 (16.4%) women developed incident diabetes over a median (interquartile range) follow-up of 11.8 (8.2-14.8) years. We identified 33 postpartum lipid species associated with GDM, including 16 inverse associations (primarily cholesterol esters and phosphatidylcholine plasmalogens), and 17 positive associations (primarily diacyglycerols and triacyglycerols). Of these, 4 were associated with risk of incident T2D and mediated about 12% of the progression from GDM to T2D. The identified lipid species modestly improved the predictive performance for incident T2D above classical risk factors when the entire follow-up period was considered. </p> <p><em><strong>CONCLUSIONS</strong></em> GDM was associated with a wide range of lipid metabolic alterations at early postpartum, among which some lipid species were also associated with incident T2D and mediated the progression from GDM to T2D. The improvements attained by including lipid species in the prediction of T2D provides new insights regarding the early detection and prevention of progression to T2D.</p>