Maternal Metabolites Associated with Gestational Diabetes Mellitus and a Postpartum Disorder of Glucose Metabolism.

Objective To identify circulating metabolites present at ~28 weeks' gestation associated with gestational diabetes mellitus (GDM) and development of a disorder of glucose metabolism 10-14 years later. Methods Conventional clinical and targeted metabolomics analyses were performed on fasting and 1-hr serum samples following a 75g glucose load at ∼28 weeks' gestation from 2,290 women who participated in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study. Postpartum metabolic traits included fasting and 2-hr plasma glucose following a 75g glucose load, insulin resistance estimated by homeostasis model assessment, and disorders of glucose metabolism (prediabetes and type 2 diabetes) during the HAPO Follow-Up Study. Results Per-metabolite analyses identified numerous metabolites, ranging from amino acids and carbohydrates to fatty acids and lipids, before and 1-hr after a glucose load that were associated with GDM as well as development of a disorder of glucose metabolism and metabolic traits 10-14 years postpartum. A core group of fasting and 1-hr metabolites mediated, in part, the relationship between GDM and postpartum disorders of glucose metabolism, with the fasting and 1-hr metabolites accounting for 15.7% (7.1%-30.8%) and 35.4% (14.3%-101.0%) of the total effect size, respectively. For prediction of a postpartum disorder of glucose metabolism, addition of circulating fasting or 1-hr metabolites at ~28 weeks' gestation showed little improvement in prediction performance compared to clinical factors alone. Conclusions The results demonstrate association of multiple metabolites with GDM and postpartum metabolic traits and begin to define the underlying pathophysiology of the transition from GDM to a postpartum disorder of glucose metabolism.