ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: Diabetes. 2019 Aug;68(8):1604–1613. doi: 10.2337/db18-1308. Epub 2019 May 24. PMID: 31127056

Maternal obesity is an important risk factor for neonatal hypoglycaemia. Maternal BMI predicts the risk of neonatal hypoglycaemia independently from maternal obesity suggesting that the link between maternal adiposity and neonatal hypoglycaemia is complex. Identifying the underlying mechanisms of maternal obesity induced neonatal hypoglycaemia may help to predict which newborns are at high risk of hypoglycaemia and improve clinical management.

This mouse study aimed to understand the impact of pre-pregnant weight gain on fetal and neonatal blood glucose levels as well as beta-cell mass and function. Prolonged pre-pregnant high fat feeding (as opposed to high fat feeding during pregnancy) in C57BL/6 mice was found to lead to fetal and neonatal hypoglycaemia as well as increased pancreatic beta-cell mass and insulin secretion. Pre-pregnant high fat feeding also led to increased expression of genes regulating the placental supply of fatty acids. When the supply of these fatty acids was blocked (by placental-specific knockout of adipose triglyceride lipase) this then reduced beta-cell mass and improved low blood glucose levels in the perinatal period. By contrast, high fat feeding during pregnancy in the same mouse line increased maternal adiposity but not neonatal hypoglycaemia.

This is the first mouse study to show that pre-pregnant high fat feeding alters fetal and neonatal glucose levels as well as pancreatic beta-cell mass. High fat feeding in adult mice is known to increase beta-cells mass and dietary fatty acids might play a role in this. This study shows that placental fatty acids play an important role in fetal pancreatic beta-cell mass and function and that pre-pregnant maternal adiposity impacts fetal and neonatal glucose physiology.