Diabetes mellitus in pregnancy

Pathophysiology

• Human placental lactogen (HPL, aka human chorionic somatomammotropin): a hormone synthesized by syncytiotrophoblasts of the placenta, which promotes the production of insulin-like growth factors.
  • Causes insulin resistance to supply growing fetus with glucose and amino acids.
  • Concurrently increases insulin levels; inability to overcome insulin resistance → gestational diabetes.

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Diagnosis

• Screening Timing: Universal at 24–28 weeks (1st prenatal visit if high-risk).
• Two-Step Protocol:
  • Initial/Screening: 1-hour 50-g OGCT; abnormal if $\ge 140\text{ mg/dL}$.
  • Confirmatory/Gold Standard: 3-hour 100-g OGTT; diagnostic if $\ge 2$ abnormal values (Fasting $\ge 95$, 1-hr $\ge 180$, 2-hr $\ge 155$, 3-hr $\ge 140\text{ mg/dL}$).
• Key Targets: Fasting $\le 95\text{ mg/dL}$, 1-hr postprandial $\le 140\text{ mg/dL}$, 2-hr postprandial $\le 120\text{ mg/dL}$.

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Treatment

• First-line: Dietary modification & moderate exercise (Diet-controlled GDM / A1GDM).
• Second-line: Insulin (drug of choice; does not cross placenta) if glycemic targets unmet after 1–2 weeks (Medication-controlled GDM / A2GDM). Metformin/glyburide are alternatives.
• Delivery:
  • A1GDM: Deliver at 39w0d–40w6d.
  • A2GDM: Deliver at 39w0d–39w6d.
  • Cesarean delivery indicated if $\text{EFW}\ge 4500\text{ g}$ to prevent shoulder dystocia.
• Postpartum: Discontinue meds immediately after delivery; perform 2-hour 75-g OGTT at 4–12 weeks postpartum to screen for DM2.

Complications

Diabetic embryopathy

• Skeletal defects
  • Caudal regression syndrome: a congenital condition characterized by the partial or complete absence of the sacrum and often of the lower lumbar spine
  • Pathophysiology: The cause of caudal regression syndrome is unknown.
  • Maternal diabetes is a known risk factor.
  • Clinical features: based on the level of the spinal lesion and disease severity
    • Lower limb deformities or foot deformities (e.g., club foot)
    • Anorectal malformations
    • Aplasia or hypoplasia of the sacrum and/or lumbosacral spine

Diabetic fetopathy

• Definition: any anomaly in a fetus associated with maternal diabetes, caused by fetal hyperinsulinemia during gestation
• Onset: second and third trimesters
• Pathophysiology: maternal hyperglycemia → fetal hyperglycemia → stimulation of fetal pancreas → fetal hyperinsulinemia → ↑ metabolic rate, oxygen consumption, and fetal hypoxemia → metabolic, respiratory, and cardiovascular complications

Manifestations

• Growth defect: fetal macrosomia
• Polyhydramnios
  • Increased maternal glucose levels increase fetal glucose levels, as well, resulting in polyuria.
• Metabolic defects
  • Neonatal hypoglycemia c
    • Maternal hyperglycemia → fetal hyperglycemia → beta cell hypertrophy and hyperfunctioning → fetal and neonatal hyperinsulinemia → transient hypoglycemia after birth (when maternal glucose supply stops)
  • Neonatal polycythemia
    • maternal hyperglycemia → chronic fetal hyperglycemia → ↑ metabolic effects and oxygen demand → fetal hypoxemia → ↑ erythropoietin concentrations→ ↑ erythrocyte count
  • Neonatal hypocalcemia and neonatal hypomagnesemia: maternal hyperglycemia → abnormal maternal calcium-phosphorus metabolism → ↑ maternal urinary Mg excretion → maternal hypomagnesemia → fetal hypomagnesemia → impaired PTH synthesis in the fetus → fetal hypocalcemia and hypomagnesemia
• Respiratory defects
  • Acute respiratory distress syndrome
• Cardiovascular defects: transient hypertrophic cardiomyopathy
  • Definition: thickening of one or both of the ventricular walls and the interventricular septum
  • Clinical features: often asymptomatic in infants but may manifest with symptoms of heart failure (e.g., tachypnea, poor feeding, irritability)
  • Pathophysiology: maternal hyperglycemia → fetal hyperglycemia → fetal hyperinsulinemia → ↑ fat and glycogen in fetal myocardial cells → thickening of ventricular walls and the intraventricular septum in utero → ↓ ventricular size → left ventricular outflow obstruction and systolic and diastolic cardiac dysfunction
  • Spontaneously regresses after birth (classically over weeks to months) as neonatal glucose/insulin levels normalize.