ABSTRACT
Diabetes Mellitus ..............................................................................................4 1.2.1 Insulin Resistance and Its Physiological Role during Pregnancy .........4 1.2.2 Glucose Metabolism in Women with GDM .........................................5 1.2.3 Mechanisms for Insulin Resistance in Normal Pregnancy
and GDM ..............................................................................................5 1.2.3.1 Placental Hormones ...............................................................5 1.2.3.2 Cytokines/Adipocytokines .....................................................6 1.2.3.3 Cytokines and Gestational Hyperglycaemia .........................6 1.2.3.4 Cytokines and Hyperglycaemia in Camden ..........................6 1.2.3.5 Cellular Mechanisms of Insulin Resistance ..........................8 1.2.3.6 Free Fatty Acids and Insulin Resistance.............................. 10 1.2.3.7 Oxidative Stress and Insulin Resistance during Normal
Pregnancy and GDM ........................................................... 10 1.2.3.8 Other Factors That Alter Insulin Resistance
in Pregnancy ........................................................................ 12 1.3 Glucose and Foetal Growth ............................................................................ 12
1.3.1 Mechanisms of Glucose Transfer ....................................................... 12 1.3.2 Foetal Glucose Metabolism ................................................................ 13
1.4 Placental Function and Foetal Growth ........................................................... 13 1.4.1 Placental Hormones ............................................................................ 13
1.4.1.1 Human Placental Lactogen and Growth Hormone .............. 13 1.4.1.2 Insulin-Like Growth Factor (IGF) System .......................... 14 1.4.1.3 Foetal Glucose-Insulin-IGF Axis and Maternal
Nutritional Supply to Foetal Growth ................................... 14 1.4.2 Cytokines/Adipocytokines and Foetal Growth .................................. 15
1.5 Maternal Hyperglycaemia and Other Factors Contributing to Foetal Overgrowth ..................................................................................................... 15 1.5.1 Foetal Overgrowth .............................................................................. 15 1.5.2 Maternal Glycaemic Status and Foetal Overgrowth .......................... 16
Normal pregnancy is marked by significant changes in maternal insulin resistance and hyperinsulinaemia from progressively increasing insulin secretion during gestation. The regulation of glucose metabolism during pregnancy is complex. After a successful implantation of a genetically normal foetus, the placenta plays a critical role in the delivery of nutrients and in the tissue-specific regulation of normal foetal growth. In addition to its metabolic and endocrine function, the placenta secretes cytokines that significantly impact foetal growth. Pregnancies complicated by gestational diabetes mellitus (GDM) have an increased risk of foetal overgrowth (macrosomia or large for gestational age birth), higher perinatal morbidity and mortality, and presage a long-term risk of developing type 2 diabetes for the mother.
