Hyperglycaemia, pregnancy outcomes and maternal metabolic disease risk during pregnancy and lactation in a lean gestational diabetes mouse model

Autor: Angela J. C. Tol, Kaja Hribar, Janine Kruit, Laura Bongiovanni, Marcel A. Vieira‐Lara, Mirjam H. Koster, Niels J. Kloosterhuis, Rick Havinga, Martijn Koehorst, Alain de Bruin, Barbara M. Bakker, Maaike H. Oosterveer, Eline M. van der Beek
Přispěvatelé: Pathobiologie, Dep Biomolecular Health Sciences, Vrije Universiteit Amsterdam, Center for Liver, Digestive and Metabolic Diseases (CLDM), Reproductive Origins of Adult Health and Disease (ROAHD)
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Journal of Physiology, 601(10), 1761-1780. Wiley-Blackwell
Journal of Physiology, 601(10), 1761-1780. BLACKWELL PUBLISHING
Tol, A J C, Hribar, K, Kruit, J, Bongiovanni, L, Vieira-Lara, M A, Koster, M H, Kloosterhuis, N J, Havinga, R, Koehorst, M, de Bruin, A, Bakker, B M, Oosterveer, M H & van der Beek, E M 2023, ' Hyperglycaemia, pregnancy outcomes and maternal metabolic disease risk during pregnancy and lactation in a lean gestational diabetes mouse model ', Journal of Physiology, vol. 601, no. 10, pp. 1761-1780 . https://doi.org/10.1113/JP284061
ISSN: 0022-3751
DOI: 10.1113/JP284061
Popis: Hyperglycaemia in pregnancy (HIP) is a pregnancy complication characterized by mild to moderate hyperglycaemia that negatively impacts short- and long-term health of mother and child. However, relationships between severity and timing of pregnancy hyperglycaemia and postpartum outcomes have not been systemically investigated. We investigated the impact of hyperglycaemia developing during pregnancy (gestational diabetes mellitus, GDM) or already present pre-mating (pre-gestational diabetes mellitus, PDM) on maternal health and pregnancy outcomes. GDM and PDM were induced in C57BL/6NTac mice by combined 60% high fat diet (HF) and low dose streptozotocin (STZ). Animals were screened for PDM prior to mating, and all underwent an oral glucose tolerance test on gestational day (GD)15. Tissues were collected at GD18 or at postnatal day (PN)15. Among HFSTZ-treated dams, 34% developed PDM and 66% developed GDM, characterized by impaired glucose-induced insulin release and inadequate suppression of endogenous glucose production. No increased adiposity or overt insulin resistance was observed. Furthermore, markers of non-alcoholic fatty liver disease (NAFLD) were significantly increased in PDM at GD18 and were positively correlated with basal glucose levels at GD18 in GDM dams. By PN15, NAFLD markers were also increased in GDM dams. Only PDM affected pregnancy outcomes such as litter size. Our findings indicate that GDM and PDM, resulting in disturbances of maternal glucose homeostasis, increase the risk of postpartum NAFLD development, related to the onset and severity of pregnancy hyperglycaemia. These findings signal a need for earlier monitoring of maternal glycaemia and more rigorous follow-up of maternal health after GDM and PDM pregnancy in humans. (Figure presented.). Key points: We studied the impact of high-fat diet/streptozotocin induced hyperglycaemia in pregnancy in mice and found that this impaired glucose tolerance and insulin release. Litter size and embryo survival were compromised by pre-gestational, but not by gestational, diabetes. Despite postpartum recovery from hyperglycaemia in a majority of dams, liver disease markers were further elevated by postnatal day 15. Maternal liver disease markers were associated with the severity of hyperglycaemia at gestational day 18. The association between hyperglycaemic exposure and non-alcoholic fatty liver disease signals a need for more rigorous monitoring and follow-up of maternal glycaemia and health in diabetic pregnancy in humans.
Databáze: OpenAIRE
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