Aetiology

During normal pregnancy, resistance to insulin action increases. In most pregnancies, pancreatic beta cells are able to compensate for increased insulin demands, and normoglycaemia is maintained. In contrast, women who develop GDM have deficits in beta-cell response leading to insufficient insulin secretion to compensate for the increased insulin demands. Risk is increased by:

  • Obesity: leads to increased insulin resistance, which is further compounded by pregnancy[4][15][16]

  • Age: due to age-related decreased pancreatic beta-cell reserve[15]

  • Prior GDM: GDM recurs in as many as 80% of subsequent pregnancies.[4][14][17]

  • Previous macrosomic baby (weighing 4.5 kg or more) [4][14]

  • Non-white ancestry or ethnicity with a high prevalence of diabetes[4][15][18]

  • Family history of type 2 diabetes (first-degree relative with diabetes)[4][14][15]

  • Polycystic ovarian syndrome: associated with insulin resistance and obesity[15][19][20]

Pathophysiology

Products of the placenta, including tumour 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.[21]​ Insulin resistance is most marked in the third trimester - the reason that screening has traditionally been performed at this point. Women who develop GDM have deficits in beta-cell function rendering them unable to adapt to pregnancy.[15] 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 recognised as GDM.

Hyperglycaemia in late pregnancy is associated with:[15][22][23]

  • Macrosomia

  • Neonatal hypoglycaemia, hyperbilirubinaemia, and hypocalcaemia

  • Adverse maternal outcomes, including gestational hypertension, pre-eclampsia, and caesarean delivery.

The Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study showed that even mild increases in maternal glycaemia raise pregnancy risk of macrosomia and related outcomes, and showed no glucose threshold values for such risks.[23]

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