Gestational Diabetes Mellitus represents a major public health concern due to adverse maternal post-partum and long-term outcome. Current strategies to manage Gestational Diabetes Mellitus fail to reduce the maternal risk to develop later impaired glucose tolerance and type 2 diabetes . In a rodent model of diet-induced gestational diabetes mellitus without obesity, we explored the perinatal metabolic adaptations in dams with gestational diabetes mellitus followed by either persistent or resolved post-partum impaired glucose tolerance . Female Sprague-Dawley rats were fed a High-Fat High-Sucrose or a Chow diet, one week before mating and throughout gestation. Following parturition, High-Fat High-Sucrose dams were randomized to two subgroups: one switched to Chow diet and the other one maintained on High-Fat High-Sucrose diet throughout lactation. Oral glucose tolerance tests were performed and plasma metabolome-lipidome were characterized at Gestation_day 12 and Lactation_day 12. We found that: 1_in gestational diabetes mellituspregnant-dams, impaired glucose tolerance was associated with incomplete fatty acid oxidation, enhanced gluconeogenesis, altered insulin signaling and oxidative stress; 2_improved glucose tolerance post-partum seemed to restore complete fatty acid oxidation along with elevation of nervonic acid-containing sphingomyelins, assumed to impart beta-cell protection; and 3_persistence of impaired glucose tolerance 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 impaired glucose tolerance evolution on maternal metabolic outcome after an episode of gestational diabetes mellitus. They suggest innovative strategies, implemented shortly after delivery and targeted on these biomarkers, should be explored to curb or delay the transition from gestational diabetes mellitus to type 2 diabetes in these mothers.

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