AUTHOR=Ludidi Asiphaphola , Siboto Anelisiwe , Nkosi Ayanda , Xulu Nombuso Duduzile , Khathi Andile , Sibiya Ntethelelo Hopewell , Ngubane Phikelelani Siphosethu TITLE=High-fat, high-carbohydrate diet-induced prediabetes preconception in Sprague–Dawley rats as a risk factor for the development of preeclampsia: assessing changes in placental metabolic insults JOURNAL=Frontiers in Nutrition VOLUME=Volume 10 - 2023 YEAR=2023 URL=https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2023.1241785 DOI=10.3389/fnut.2023.1241785 ISSN=2296-861X ABSTRACT=Introduction: Hyperglycaemia preconception deranges the establishment of a functional placenta, however, the risk of developing preeclampsia (PE) in prediabetic patients remains obscure. The aim was to assess abnormal placental changes as a risk factor for the development of PE in high-fat-, high-carbohydrate (HFHC) diet-induced prediabetic (PD) rats. Methods: HFHC diet-induced female prediabetic Sprague-Dawley rats were mated and blood glucose concentrations, mean arterial pressure (MAP) and body weights were monitored on gestational day (GND) 0, 9 and 18. On GND 18, animals were euthanized. Blood and placentas were collected for biochemical analysis. Results: Prediabetic rats showed significantly increased blood glucose concentration, proinflammatory cytokines, MAP, placental weight and foetoplacental ratio compared to non-prediabetic (NPD) rats. Prediabetic rats showed significantly decreased placental vascular endothelial growth factor receptor 1 (VEGFR1) and placental growth factor (PLGF) and plasma nitric oxide (NO) compared to NPD. Discussion: Prediabetes may have promoted endothelial dysfunction in the placenta and hypoxia thus reducing PLGF and VEGFR1 which may have promoted proinflammation, endothelial dysfunction associated with NO decline and hypertension which is also observed in preeclamptic patients. Prediabetes may have promoted lipogenesis in placentas and foetuses which may have induced macrosomia and IUGR also observed in preeclamptic patients. Findings from this study highlight the need for screening and monitoring of prediabetes during pregnancy to reduce the risk of developing preeclampsia.