LAUSR

Abstract BACKGROUND Neonatal Diabetes (ND) is rare with incidence estimated at 1 / 100,000-500,000 live births. Duration of ND and insulin requirements vary with average therapy lasting 3 months. Genetic mutations are reported in 90% of transient forms with mutations in the region of 6q24 accounting for 70% of mutations. Sulfonylurea is the preferred initial treatment, but when patients fail to respond, insulin is required, raising difficulties in treatment and blood glucose (BG) monitoring. CLINICAL CASE A 2040 gram male was delivered at 37 weeks gestation to a 40 year old mother. Prenatal history included IUGR and the infant developed persistent hypoglycemia on day of life (DOL) two characterized by pallor, apnea and hypothermia. He was acidotic with multiple BG values ≥ 250mg/dl. He was placed NPO without dextrose in his TPN. On DOL four he resumed enteral feeds but BG rose to 297mg/dl with concurrent insulin level of 0.07 mIU/L and undetectable C-Peptide. He was started on continuous IV insulin infusion ranging from 0.05u/k/hr-0.2units/k/hr. He received one dose of Regular insulin (0.2 units (U) resulting in dramatic BG drop < 50 mg/dl requiring IV dextrose bolus. Enteral feeds resumed on DOL 10 along with Glyburide at 0.1mg/kg BID. BG rose to ≥250 mg/dl despite increasing Glyburide to 2mg/kg/day and C-Peptide remained undetectable. Continuous IV insulin infusion was resumed ranging from 0.01- 0.05u/k/hr. Glyburide was discontinued after 2 weeks due to ineffectiveness. Genetic testing confirmed a 6q24 mutation consistent with transient ND, overexpression of 6q genes, and a suspected methylation disorder. Because overexpression down-regulates insulin secretion potentially leading to a poor response to Sulfonylurea, a second Sulfonylurea trial was attempted, but also failed. The infant was started on continuous subcutaneous insulin infusion (insulin pump) but multiple site failures prevented effective glycemic control and continuous IV insulin infusion was resumed. After 3 months, continuous IV insulin infusion rate had increased to 1.5 units/day. With increasing body weight and insulin requirements, he was transitioned to 1 unit insulin Glargine daily and then BID. BG remained in the 100 - 300 mg/dl range on a program of Glargine 1 unit SQ BID plus 1 unit of Regular insulin if BG ≥500 mg/dl. He is now 5 months old with an increasing need for insulin and A1c = 9.0%. Because his pre-prandial BG ranged from 300-400mg/dl without hypoglycemia, the Glargine dose was increased to 1.5 units SQ in the AM and 1.0 units SQ in the PM. CONCLUSION This is the rare case of a patient with ND having increasing insulin requirements at 5 months of age who did not respond to Sulfonylurea treatment. Predicting how long insulin requirements will last is currently unknown. The 6q24 mutation is involved in the mutation of a protein that induces apoptosis of cells involved in insulin secretion from beta cells.