<ns3:p>Gestational Diabetes Mellitus (GDM) is the most frequent pregnancy-related medical issue and presents significant risks to both maternal and foetal health, requiring monitoring and management during pregnancy. The prevalence of GDM has surged globally in recent years, mirroring the rise in diabetes and obesity rates. Estimated to affect from 5% to 25% of pregnancies, GDM impacts approximately 21 million live births annually, according to the International Diabetes Federation (IDF). However, consensus on diagnostic approaches remains elusive, with varying recommendations from international organizations, which makes the comparison between research complicated. Compounding concerns are the short-term and long-term complications stemming from GDM for mothers and offspring. Maternal outcomes include heightened cardiovascular risks and a notable 70% risk of developing Type 2 Diabetes Mellitus (T2DM) within a decade postpartum. Despite this, research into the metabolic profiles associated with a previous GDM predisposing women to T2D remains limited. While genetic biomarkers have been identified, indicating the multifaceted nature of GDM involving hormonal changes, insulin resistance, and impaired insulin secretion, there remains a dearth of exploration into the enduring health implications for both mothers and their children. Furthermore, offspring born to mothers with GDM have been shown to face an increased risk of obesity and metabolic syndrome during childhood and adolescence, with studies indicating a heightened risk ranging from 20% to 50%. This comprehensive review aims to critically assess the current landscape of Gestational Diabetes Mellitus (GDM) research, focusing on its prevalence, diagnostic challenges, and health impacts on mothers and offspring. By examining state-of-the-art knowledge and identifying key knowledge gaps in the scientific literature, this review aims to highlight the multifaceted factors that have hindered a deeper understanding of GDM and its long-term consequences. Ultimately, this scholarly exploration seeks to promote further investigation into this critical area, improving health outcomes for mothers and their children.</ns3:p> 

Gestational Diabetes Mellitus: Unveiling Maternal Health Dynamics from Pregnancy Through Postpartum Perspectives

Increased maternal food intake is considered a normal pregnancy adjustment. However, the overavailability of nutrients may lead to dysregulated fetal development and increased adiposity, with long-lasting effects on offspring in later life. Several gut-hormone molecules regulate maternal appetite, with both their orexigenic and anorectic effects being in a state of sensitive equilibrium. The aim of this manuscript is to systematically review literature on the effects of maternal gut-hormone molecules on fetal growth and metabolism, birth weight and the later metabolic health of offspring. Maternal serum ghrelin, leptin, IGF-1 and GLP-1 appear to influence fetal growth; however, a lack of consistent and strong correlations of maternal appetite axis hormones with birth weight and the concomitant correlation with fetal and birth waist circumference may suggest that these molecules primarily mediate fetal energy deposition mechanisms, preparing the fetus for survival after birth. Dysregulated intrauterine environments seem to have detrimental, sex-dependent effects on fetal energy stores, affecting not only fetal growth, fat mass deposition and birth weight, but also future metabolic and endocrine wellbeing of offspring. 

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The Gestational Effects of Maternal Appetite Axis Molecules on Fetal Growth, Metabolism and Long-Term Metabolic Health: A Systematic Review

Background Intrauterine hyperglycemia can harm a fetus's growth and development, and this can be seen in the umbilical cord blood metabolism disorder. However, the metabolites and metabolic mechanisms involved in the condition remain unknown. Methods Targeted metabolomics using liquid chromatography and MetaboAnalyst were conducted in this study to explore differences in metabolites and metabolic pathways between individuals with hyperglycemia or well-controlled gestational diabetes mellitus (GDM) and healthy controls. Results Univariate analysis found that the hyperglycemic and healthy control groups differed in 30 metabolites, while the well-controlled GDM and the healthy control groups differed only in three metabolites-ursodeoxycholic acid, docosahexaenoic acid, and 8,11,14-eicosatrienoic acid. Most of these metabolic variations were negatively associated with neonatal weights. Further research showed that the variations in the metabolites were primarily associated with the metabolic pathways of linoleic acid (LA) and alpha-linolenic acid (ALA). Conclusion Gestational hyperglycemia and well-controlled GDM, which may play a major role by inhibiting the LA and ALA metabolic pathways, have detrimental effects on cord blood metabolism. Impact The main point of this paper is that intrauterine hyperglycemia has a negative effect on cord blood metabolism mainly through the linoleic acid and alpha-linolenic acid metabolic pathways. This is a study to report a new association between well-controlled GDM and cord blood metabolism. This study provides a possible explanation for the association between intrauterine hyperglycemia and neonatal adverse birth outcomes.

Umbilical cord blood metabolomics: association with intrauterine hyperglycemia.

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Umbilical cord blood metabolomics: association with intrauterine hyperglycemia.