Metabolite Signatures in Postpartum Prediabetes and Diabetes Among Indian Women With Prior Gestational Diabetes Mellitus: Insights From CHIP-F Study.

AIMS: Gestational diabetes mellitus (GDM) increases the risk of postpartum dysglycaemia. This study investigates candidate metabolites and perturbed metabolic pathways associated with postpartum prediabetes/diabetes among high-risk Indian/South-Asian women with prior GDM, a largely unexplored population. MATERIALS AND METHODS: In this nested case-control study within the Cohort of Indian Women with Hyperglycaemia in Pregnancy and their Families (CHIP-F), untargeted metabolomics (UPLC-MS/MS) was performed on plasma samples from 216 women with prior GDM, which included 22 participants with postpartum diabetes, 88 with prediabetes and 106 with normoglycaemia. RESULTS: Untargeted metabolomics combined with machine learning approach revealed distinct metabolic alterations associated with postpartum dysglycaemia (prediabetes/diabetes) among women with prior GDM. After adjustment for age, body mass index, family history of diabetes, and postpartum duration, each 1-standard deviation increase in the log-transformed concentrations of Tyrosine (aOR = 1.71, 95% CI: 1.01-2.91) and L-Kynurenine (aOR = 1.69, 1.02-2.80) was associated with higher odds of diabetes. Similarly, higher concentrations of 2-Aminoisobutyric acid (aOR = 1.50, 1.09-2.06), Butyrylcarnitine (aOR = 1.99, 1.44-2.75), L-Norleucine (aOR = 1.96, 1.41-2.72), and Propionylcarnitine (aOR = 1.94, 1.41-2.67) were associated with higher odds of prediabetes. Pathway analysis revealed potential dysregulation of aromatic amino acids (AAAs) metabolism in prediabetes. In diabetes, in addition to dysregulation of AAAs, potential lipid metabolic disturbances were also present. CONCLUSIONS: This study identified distinct candidate metabolic signatures associated with postpartum prediabetes and diabetes in Indian/South-Asian women with a history of prior GDM, highlighting early disruptions in AAAs and lipid metabolism.