Neonatal diabetes mellitus, defined as insulin-sensitive hyperglycemia involving the activating mutations in the KCNJ11 gene encoding Kir 6.2, is diagnosed within the first six months of life presenting with glucosuria, polyuria, dehydration, failure to thrive, and diabetic ketoacidosis [1]. Treatment with insulin results in dramatic catch-up growth; insulin may be discontinued in about half these patients, as blood glucose is well-controlled on sulfonylureas (SUs).

We report a case of neonatal diabetes in a 4-month-old baby girl presenting with diabetic ketoacidosis due to p.R201H mutation in the KCNJ11 gene, who was successfully changed from subcutaneous insulin to oral glibenclamide on an outpatient basis.

The patient, who was being treated elsewhere as Type 1 diabetic, had an HbA1c of 11.6% with low serum c-peptide levels (<0.3 ng/mL) on referral. Since autoimmune diabetes is less common before six months of age, we considered other possible causes of diabetes. While awaiting results of genetic analysis, she was initiated on oral glibenclamide (as a powder dissolved in water) in a dose of 0.3 mg/kg/day, in three divided doses. Strict self monitoring of blood glucose was done and the insulin was gradually tapered off over next few days. Within four days of starting glibenclamide, repeat serum c-peptide levels done were better (2.25 ng/mL), indicating increased endogenous production of insulin. Genetic testing of both parents was negative for the mutations.

Presently, the patient is doing well, gaining weight, and is continuing on glibenclamide with a latest HbA1c of 7.6% and serum c-peptide level of 2.38 ng/mL. We therefore suggest an outpatient protocol for changing these patients from insulin to Sulfonylureas(SUs) [2].

SUs are introduced gradually over a period of weeks as an outpatient. Glibenclamide dose is increased each week by 0.2 mg per kg per day in divided doses up to a total daily dose of 1.0 mg per kg per day. It has been found that the pre-breakfast glucose may be very slow to fall and pre-lunch or pre-evening meal glucose values fall more rapidly and are generally a better marker of response to SUs. In some patients there may be initial diarrhea but this settles on its own. Care must be taken to recognize and treat hypoglycemia including the use of 0.5-1 mg glucagon injection for emergency use if unable to take oral carbohydrate. The physician should see the patient every week, and be accessible by phone during the transfer.

We emphasize the need for medical practitioners to consider molecular testing for all patients who present with diabetes below 6 months of age as this will facilitate accurate diagnosis and appropriate therapy.

1. Flanagan SE, Edghill EL, Gloyn AL, Ellard S, Hattersley AT. Mutations in KCNJ11, which encodes Kir6.2, are a common cause of diabetes diagnosed in the first 6 months of life, with the phenotype determined by genotype. Diabetologia. 2006;49:1190-7.