Programming of cardiometabolic health: the role of maternal and fetal hyperinsulinaemia

Abstract

Obesity and gestational diabetes during pregnancy have multiple short- and long-term consequences for both mother and child. One common feature of pregnancies complicated by maternal obesity and gestational diabetes is maternal hyperinsulinaemia, which has effects on the mother and her adaptation to pregnancy. Even though insulin does not cross the placenta insulin can act on the placenta as well affecting placental growth, angiogenesis and lipid metabolism. Obese and gestational diabetic pregnancies are often characterised by maternal hyperglycaemia resulting in exposure of the fetus to high levels of glucose, which freely crosses the placenta. This leads to stimulation of fetal ß-cells and insulin secretion in the fetus. Fetal hyperglycaemia/hyperinsulinaemia has been shown to cause multiple complications in fetal development, such as altered growth trajectories, impaired neuronal and cardiac development and early exhaustion of the pancreas. These changes could increase the susceptibility of the offspring to develop cardiometabolic diseases later in life. In this review, we aim to summarize and review the mechanisms by which maternal and fetal hyperinsulinaemia impact on (i) maternal health during pregnancy; (ii) placental and fetal development; (iii) offspring energy homeostasis and long-term cardiometabolic health; (iv) how interventions can alleviate these effects.

Keywords: developmental programming; fetal hyperinsulinaemia; gestational diabetes; maternal hyperinsulinaemia; pregnancy.

Figure 1

The effect of maternal hyperinsulinaemia and hyperglycaemia on the fetus. Glucose and insulin can act on the placenta and thereby indirectly influence fetal development. Insulin cannot cross the placenta; however, glucose can pass through the placenta leading to increased glucose levels in the fetus and resulting in fetal hyperinsulinaemia.

Figure 2

Effects of diabetes/obesity on the maternal adaptation to pregnancy. Physiological and pathological changes in pregnancy are summarised.

Figure 3

The human placenta and its barriers between maternal and fetal circulation. The villous structure of the human placenta is shown and zooming in highlights the different cellular barriers between maternal and fetal blood (adapted from Rossant & Cross 2001).

Figure 4

Effects of maternal and fetal hyperinsulinaemia in an obese/diabetic pregnancy.