Treatment of Hyperglycemia in a 7-Year-Old Child Diagnosed With Neonatal Diabetes

Permanent neonatal diabetes is persistent, insulin-requiring hyperglycemia occurring before 1 month of life. Recent studies have identified activating mutations in KCNJ11 encoding the Kir6.2 subunit of the ATP-sensitive K⁺ channel as a common cause of neonatal diabetes (1,2,3,4,5). These patients can be successfully managed with oral sulfonylureas rather than insulin (2,4,6,7). We describe our experience with a 7-year-old Mexican-American girl diagnosed with insulin-dependent diabetes at 2 weeks of age when she presented with a respiratory infection. Her blood glucose level was 442 mg/dl, C-peptide 0.33 ng/ml (ref. 0.8–4), insulin 3.1 uU/ml (ref. 0–22), and HbA_1c (A1C) 7.7% (ref. <6.4), and she had negative diabetes autoantibodies. Her mother was diagnosed with insulin-dependent diabetes at 6 months of age. The propositus was evaluated at the pediatric diabetes center at Loma Linda University at the age of 6 years, and DNA testing revealed the presence of the permanent neonatal diabetes–associated mutation Arg201His in KCNJ11 in both her and her mother (2). Glucagon and mixed-meal glucose tolerance testing did not show an increment in C-peptide from the baseline value. Insulin was weaned and discontinued over 2 weeks, with a starting glyburide dose of 1.25 mg b.i.d. (0.05 mg · kg⁻¹ · day⁻¹) and incremental increase to the current dose of 3.5 mg glyburide b.i.d. Previously, the patient’s A1C on insulin ranged from 7.1 to 11.5%. Off insulin, and over the past 24 months, her quarterly A1C range was 5.1–6.3%, with no record or symptoms suggestive of hypoglycemia. Our results were consistent with other reports in the literature (2,4,6,7). The patient and her family were overwhelmingly pleased with the discontinuation of insulin, which they referred to as “a miracle.”