Etiology
During normal pregnancy, resistance to insulin action increases. In most pregnancies, pancreatic beta cells are able to compensate for increased insulin demands, and normoglycemia is maintained. In contrast, women who develop gestational diabetes mellitus (GDM) have deficits in beta-cell response leading to insufficient insulin secretion to compensate for the increased insulin demands. Risk of GDM is associated with:
Age: due to age-related decreased pancreatic beta-cell reserve[14]
Obesity: leads to increased insulin resistance, which is further compounded by pregnancy[14][15]
Polycystic ovarian syndrome: associated with insulin resistance and obesity[14][16][17]
Family history of type 2 diabetes[14]
Previous macrosomic baby (weighing 4.5 kg or more)[19]
Lack of physical activity: exercise increases insulin sensitivity and may impact body weight[20][21]
Prior GDM: GDM recurs in as many as 80% of subsequent pregnancies.[22]
Pathophysiology
Substances produced by the placenta, including tumor necrosis factor-alpha (TNF-alpha) and human placental lactogen (also known as human chorionic somatomammotropin), are thought to play key roles in inducing maternal insulin resistance.[23] There is a 40% to 50% increase in insulin resistance with advancing gestation, in both women with normal glucose tolerance and those with GDM, with rapid insulin resistance reversal after delivery.[24] Insulin resistance is most marked in the third trimester - the reason that screening has traditionally been performed at this point. Most women who develop GDM have higher prepregnancy insulin resistance and have deficits in beta-cell function rendering them unable to adapt to pregnancy.[14][24] In GDM, as in type 2 diabetes, the deficit in beta-cell function is usually multifactorial and polygenetic. However, unmasked by the increased insulin needs of pregnancy, autoimmune diabetes and maturity-onset diabetes of youth (MODY) may occasionally be first recognized as GDM. Hyperglycemia in late pregnancy is associated with macrosomia and neonatal hypoglycemia, hyperbilirubinemia, and hypocalcemia, as well as adverse maternal outcomes, including gestational hypertension, preeclampsia, and cesarean delivery.[14][25][26] The Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study showed that even mild increases in maternal glycemia raise pregnancy risk of macrosomia and related outcomes, and showed no glucose threshold values for such risks.[26]
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