Abstract
Approximately, 35% of women with Gestational Diabetes (GDM) progress to Type 2 Diabetes (T2D) within 10 years. However, links between GDM and T2D are not well understood. We used a well-characterised GDM prospective cohort of 1035 women following up to 8 years postpartum. Lipidomics profiling covering >1000 lipids was performed on fasting plasma samples from participants 6-9 week postpartum (171 incident T2D vs. 179 controls). We discovered 311 lipids positively and 70 lipids negatively associated with T2D risk. The upregulation of glycerolipid metabolism involving triacylglycerol and diacylglycerol biosynthesis suggested activated lipid storage before diabetes onset. In contrast, decreased sphingomyelines, hexosylceramide and lactosylceramide indicated impaired sphingolipid metabolism. Additionally, a lipid signature was identified to effectively predict future diabetes risk. These findings demonstrate an underlying dyslipidemia during the early postpartum in those GDM women who progress to T2D and suggest endogenous lipogenesis may be a driving force for future diabetes onset.
Highlights
Gestational diabetes mellitus (GDM) develops during pregnancy, affecting 1–14% of all pregnancies depending on diagnostic criteria and the population characteristics (Chen et al, 2018; Melchior et al, 2017)
A lipid signature associated with future diabetes risk was uncovered which contributes new knowledge to understanding the aetiology of diabetes in women associated with GDM
Our data indicate that women with recent GDM who later develop new onset type 2 diabetes (T2D) have clear differences in their lipidome compared to controls after delivery
Summary
Gestational diabetes mellitus (GDM) develops during pregnancy, affecting 1–14% of all pregnancies depending on diagnostic criteria and the population characteristics (Chen et al, 2018; Melchior et al, 2017). The majority of women with a history of GDM were not known to have overt diabetes before pregnancy and return to non-diabetes post-delivery. Women with a history of GDM are ~7 times more likely to develop type 2 diabetes (T2D) during the child-bearing years compared to women who had no previous GDM (Chen et al, 2018; Bellamy et al, 2009; Gunderson et al, 2007). It is estimated that 35–50% of women with GDM may progress to T2D within 10 years after delivery (Bellamy et al, 2009; Tobias, 2018). It is critical to uncover the underlying metabolic changes and understand the distinctive pathophysiology in T2D progression/development following GDM
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