A specific metabolomic and lipidomic signature reveals the post-partum resolution of gestational diabetes mellitus or its evolution to Type 2 Diabetes in rat.

Abstract

Gestational Diabetes Mellitus (GDM) represents a major public health concern due to adverse maternal post-partum and long-term outcome. Current strategies to manage GDM fail to reduce the maternal risk to develop later impaired glucose tolerance (IGT) and type 2 diabetes (T2D). In a rodent model of diet-induced GDM without obesity, we explored the perinatal metabolic adaptations in dams followed by either persistent or resolved post-partum IGT. Female Sprague-Dawley rats were fed a High-Fat High-Sucrose (HFHS) or a Chow (CTL) diet, one week before mating and throughout gestation (G). Following parturition, HFHS dams were randomized to two subgroups: one switched to Chow diet and the other one maintained on HFHS diet throughout lactation (L). Oral glucose tolerance tests (OGTT) were performed and plasma metabolome-lipidome were characterized at G12 and L12. We found that: (1) in GDM pregnant-dams, IGT was associated with incomplete fatty acid oxidation (FAO), enhanced gluconeogenesis, altered insulin signaling and oxidative stress; (2) improved glucose tolerance post-partum seemed to restore complete FAO along with elevation of nervonic acid-containing sphingomyelins, assumed to impart β-cell protection; and (3) persistence of IGT after delivery was associated with metabolites known to predict the early onset of insulin and leptin resistance, with maintained liver dysfunction. Our findings shed light on the impact of post-partum IGT evolution on maternal metabolic outcome after an episode of GDM. They suggest innovative strategies, implemented shortly after delivery and targeted on these biomarkers, should be explored to curb or delay the transition from GDM to T2D in these mothers.