Metabolic Adaptations to Pregnancy in Healthy and Gestational Diabetic Pregnancies: The Pancreas - Placenta Axis

Normal pregnancy is associated with increased insulin resistance as a metabolic adaptation to the nutritional demands of the placenta and fetus, and this is amplified in obese mothers. Insulin resistance is normally compensated for by an adaptive increase in pancreatic beta-cell mass together with enhanced glucose-stimulated insulin release. Placentally-derived hormones and growth factors are central to the altered pancreatic morphology and function. A failure of beta-cells to undergo adaptive change after the first trimester has been linked with gestational diabetes. In the pregnant mouse, an increase in beta-cell replication contributes to a 2-3-fold increase in mass peaking in late gestation, depending on the proliferation of existing beta-cells, the differentiation of resident progenitor beta-cells, or islet cell trans- differentiation. Using mouse models and human studies placenta- and islet of Langerhans-derived mole cules have been identified that are likely to contribute to the metabolic adaptations to pregnancy and whose physiology is altered in the obese, glucose-intolerant mother. Maternal obesity during pregnancy can create a pro-inflammatory environment that can disrupt the response of the beta-cells to the endocrine signals of pregnancy and limit the adaptive changes in beta-cell mass and function, resulting in an increased risk of gestational diabetes.

Automated summary

Normal pregnancy is associated with increased insulin resistance which is normally compensated for by an adaptive increase in pancreatic beta-cell mass. Placenta-derived hormones and growth factors play a key role in altering pancreatic morphology and function. However, maternal obesity can disrupt this adaptive process, leading to an increased risk of gestational diabetes.