Neonatal Diabetes

Rare form of monogenic diabetes much of which is caused by mutations in the glucose sensing mechanism e.g. in the ATP sensitive K channel

Aetiology

  • Monogenic mutation
  • Many genes responsible, 35 genes can explain up to 82% of neonatal diabetes

Pathophysiology

  • The KATP channel consists of:
    • An inward rectifier (pore) subunit (KIR) - Kir6
    • A sulphonylurea receptor (regulatory subunit) - SUR1
    • Both are required to form a functional channel
  • In humans, Kir6.2 mutations can lead to neonatal diabetes
    • Due to constitutively activated KATP channels or increase in KATP numbers

Clinical presentation

  • Diabetes diagnosed < 6 months (chance of T1DM at this age is >1%)
  • Polydipsia, polyuria
  • Dehydration
  • DKA

Investigations

  • Blood glucose

Management

  • In many of these patients the β-cells are responsive to sulphonylureas which inhibit KATP - recover euglycaemia fairly quickly
  • Patients previously misdiagnosed as T1DM who are on insulin can safely switch to high dose SUs

Other KATP channel mutations

  • Some Kir6.2 or SUR1 mutations lead to congenital hyperinsulinism
  • Congenital hyperinsulinism is characterised by inappropriate and unregulated insulin secretion, which results in severe, persistent hypoglycemia in newborn babies, infants, and children
  • Management: diazoxide stimulates KATP so can help inhibit insulin secretion if channels are still getting to the membrane