Lecture presented by Fabrizio Barbetti summarized below:
A sometimes overlooked cause of neonatal diabetes is monogenic, or a mutation in one gene. Neonatal diabetes is defined as diabetes occurring up to 180 days of life and has an incidence of 1:210,000 births. There may be a resulting defect in the beta cell, or a genetic defect in insulin action.
One type results from complete glucokinase deficiency due to a mutation in the gene encoding ATP-sensitive K+ channel subunit Kir6.2. In patients with this KCNJ11 mutation, many may be successfully weaned from insulin to a sulfonylurea such as glyburide or gliclazide. Doses up to 45 mg/day glyburide or 720 mg/day gliclazide have been used in adults. (Up to 2 - 2.5 mg/kg/day glyburide) Glyburide may be dissolved in water at 5 mg/mL and mixed in formula or mother's milk for infants.
An interesting link between monogenic DM and motor/developmental delay was discussed. The subunit Kir6.2 is found on other cells(other than the beta cell) such as neuronal cells. Some patients weaned from insulin do much better in regards to motor co-ordination when on glyburide. Genetic testing appears to be worthwhile, although our capability here in North America was not discussed.
