Pathophysiology
Clinical meaning
Gestational diabetes mellitus (GDM) is a carbohydrate intolerance of variable severity that is first recognized during pregnancy. The condition affects approximately 3-9% of all pregnancies and is one of the most common metabolic complications of the antepartum period. During normal pregnancy, the placenta produces hormones that are essential for fetal growth, including human placental lactogen (hPL), cortisol, estrogen, and progesterone. These hormones create a progressive state of insulin resistance that begins around 20-24 weeks of gestation and intensifies throughout the third trimester. Human placental lactogen is the primary diabetogenic hormone; it acts as an insulin antagonist by decreasing maternal glucose uptake at the cellular level, effectively diverting glucose across the placenta to the developing fetus. In a healthy pregnancy, the maternal pancreas compensates by increasing insulin production two to three times above normal baseline. However, when the maternal pancreatic beta cells cannot produce sufficient insulin to overcome the placental hormone-mediated insulin resistance, blood glucose levels rise and gestational diabetes develops. At the cellular level, insulin resistance in GDM involves impaired post-receptor signaling in the insulin receptor substrate pathway, specifically reduced...