A pregnant woman at 30 weeks with pre-gestational Type 1 diabetes presents with HbA1c of 8.5%. She is on insulin lispro and insulin detemir. Regarding insulin pharmacokinetics in pregnancy, why does insulin requirement increase progressively during the second and third trimesters?
- A Placental insulinase destroys maternal insulin, reducing its bioavailability
- B Human placental lactogen (hPL), cortisol, oestrogen, and progesterone collectively cause peripheral insulin resistance by inhibiting post-receptor insulin signalling (IRS-1 phosphorylation) ✓
- C Increased renal clearance of insulin due to increased GFR in pregnancy reduces circulating insulin levels
- D Increased energy utilisation by the growing fetus depletes maternal glucose, triggering compensatory gluconeogenesis that overwhelms insulin action
Explanation
Insulin resistance in pregnancy is a physiological adaptation driven by contra-insulin hormones produced by the placenta: human placental lactogen (hPL, also called human chorionic somatomammotropin) is quantitatively the most important; cortisol (elevated in pregnancy) activates hepatic gluconeogenesis and reduces peripheral glucose uptake; progesterone and oestrogen also contribute to reduced insulin sensitivity. These hormones impair post-receptor insulin signalling — particularly reducing IRS-1 (insulin receptor substrate-1) tyrosine phosphorylation and downstream PI3K/Akt activation — causing progressive insulin resistance that peaks at 26–32 weeks as hPL levels reach maximum.
Reference: Williams Obstetrics, 26th ed.
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Written and medically reviewed by the StethoPrep medical team.