Abstract
Gestational diabetes mellitus (GDM) is the most common metabolic complication of pregnancy, with a prevalence that has increased significantly in the last decade, coming to affect 12–18% of all pregnancies. GDM is believed to be the result of a combination of genetic, epigenetic and environmental factors. Following the identification of susceptibility genes for type 2 diabetes by means of genome-wide association studies, an association has also been demonstrated between some type 2 diabetes susceptibility genes and GDM, suggesting a partial similarity of the genetic architecture behind the two forms of diabetes. More recent genome-wide association studies, focusing on maternal metabolism during pregnancy, have demonstrated an overlap in the genes associated with metabolic traits in gravid and non-gravid populations, as well as in genes apparently unique to pregnancy. Epigenetic changes—such as DNA methylation, histone modifications and microRNA gene silencing—have also been identified in GDM patients. Metabolomics has been used to profile the metabolic state of women during pregnancy, based on the measurement of numerous low-molecular-weight metabolites. Measuring amino acids and conventional metabolites has revealed changes in pregnant women with a higher insulin resistance and high blood glucose levels that resemble the changes seen in non-gravid, insulin-resistant populations. This would suggest similarities in the metabolic profiles typical of insulin resistance and hyperglycemia whether individuals are pregnant or not. Future studies combining data obtained using multiple technologies will enable an integrated systems biology approach to maternal metabolism during a pregnancy complicated by GDM. This review highlights the recent knowledge on the impact of genetics and epigenetics in the pathophysiology of GDM and the maternal and fetal complications associated with this pathology condition.
Highlights
Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance developing or first recognized during pregnancy that is not clearly overt diabetes [1]
Intriguing results were generated by a study on the genetic variants in GCK and TCF7L2, and their possible association with glucose levels on oral glucose tolerance tests (OGTTs) performed in pregnant women participating in the Hyperglycemia and Adverse Pregnancy Outcomes Study (HAPO) [19]
MEST methylation was found significantly lower in the blood of adults with obesity than in normal-weight controls. These results indicate that intrauterine exposure to GDM has lasting effects on the epigenome of the offspring, and that epigenetic malprogramming of MEST can contribute to predisposing individuals to obesity later in life
Summary
Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance developing or first recognized during pregnancy that is not clearly overt diabetes [1]. A significant association emerged between known T2D variants and GDM This association with GDM was strong for the genetic variants in CDKAL (a type of variant affecting beta cell survival) and MTNR1B (a variant associated with high fasting plasma glucose and insulin levels). In a study on GDM, the frequency of IRS-1 gene polymorphism was significantly higher in women with GDM than in pregnant women with a normal glucose tolerance, suggesting a role for this polymorphism in the onset of GDM as well as type 2 diabetes mellitus [17]. Intriguing results were generated by a study on the genetic variants in GCK and TCF7L2, and their possible association with glucose levels on oral glucose tolerance tests (OGTTs) performed in pregnant women participating in the Hyperglycemia and Adverse Pregnancy Outcomes Study (HAPO) [19].
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