Neonatal Diabetes Mellitus

Neonatal diabetes is insulin requiring hyperglycaemia presenting before 6 months of age (rarely up to 12 months).

• Incidence about 1 in 90,000 to 160,000 births.
• Transient (50%): imprinting abnormalities at 6q24 (PLAGL1/HYMAI), remits by 12 weeks and may relapse in adolescence.
• Permanent: KCNJ11 and ABCC8 (KATP channel activating mutations, 40%), INS, GCK, EIF2AK3 (Wolcott Rallison), FOXP3 (IPEX), GLIS3, PDX1.
• Syndromic: DEND (developmental delay, epilepsy, neonatal diabetes).

• Intrauterine growth restriction, failure to thrive, dehydration, hyperglycaemia, ketoacidosis.
• Developmental delay and seizures in KCNJ11 (DEND).
• Skeletal dysplasia, liver failure in Wolcott Rallison; enteropathy and eczema in IPEX.

• Glucose above 200 mg/dL on 2 occasions in the first 6 months.
• Urgent molecular genetic testing (do not wait for results before starting therapy).
• Islet antibodies negative; C peptide low or detectable.
• Screen for associated features: pancreas imaging, liver tests, EEG.

• Acute: IV insulin 0.05 to 0.1 unit/kg/h with fluids if ketoacidotic, subcutaneous insulin after.
• KCNJ11 or ABCC8: switch to sulfonylurea (glibenclamide 0.1 to 0.2 mg/kg/day, titrate up to 1 mg/kg/day in divided doses), successful in over 90% and may improve neurological features.
• Transient: insulin until remission, then monitor for relapse.
• Pump or glargine with frequent feeds in other forms; continuous glucose monitoring.
• Genetic counselling. Follow up development and screening for complications.