Method of treating neonatal diabetes with oral medication developed by UC Davis Children's Hospital physician
Neonatal diabetes is an extremely rare condition, and infants who suffer from it typically require insulin injections to survive. Treating these infants with an oral medication — which dramatically improves their quality of life — has been successful in only a handful of children worldwide.
Now a team of researchers led by a physician at UC Davis Children's Hospital has for the first time rapidly transitioned an infant with neonatal diabetes from injected insulin to a generic oral medication in an outpatient setting. The report on the case appears online in the journal Pediatric Diabetes and will appear in a print edition later this year.
"It's devastating for children to have to take insulin shots to control their diabetes, and often more devastating for their parents," said lead study author and UC Davis Children's Hospital assistant professor of pediatric endocrinology Andrew Bremer.
"It can dramatically change a child's life to be on an oral medication instead of injected insulin. If they're in school, they can go to the nurse to get a pill instead of a shot. Furthermore, they can spend the night at a friend's house without worrying about whether their friend's parents can correctly administer insulin injections. And, the pills are cheaper and often provide better diabetes control," Bremer said.
Transitioning children with neonatal diabetes from insulin injections to oral medication typically occurs either in an inpatient setting or over a prolonged course of time in an outpatient setting, both of which generate added stress to the patients and their families.
Permanent neonatal diabetes occurs in as few as 1 in 500,000 infants. The condition is distinct from both transient neonatal diabetes, which is also caused by a genetic anomaly but resolves after about 12 weeks of age, and type 1 diabetes, an autoimmune condition.
—Andrew Bremer, lead study author
Also known as insulin-sensitive hyperglycemia, permanent neonatal diabetes has been linked to mutations in several different genes, including KCNJ11. A defect in KCNJ11, which results in the disruption of normal insulin secretion by the pancreas, is thought to be responsible for as many as 50 percent of the cases of permanent neonatal diabetes.
Bremer saw the patient, a 20-week-old girl with no family history of type 1 diabetes, for care during an episode of diabetic ketoacidosis in the course of a fellowship at UCSF Children's Hospital. Diabetic ketoacidosis, a type of diabetic coma, occurs when the body burns its own fat stores for energy instead of food.
The child was treated for diabetic ketoacidosis with insulin, even though she tested negative for type 1 diabetes-associated autoimmune antibodies. A subsequent molecular genetic analysis revealed a mutation in the KCNJ11 gene.
Bremer and his team started the infant on a trial of oral glyburide tablets at 18 months of age as an outpatient, and carefully titrated, or concentrated, the medication's dosage. Two weeks after the initiation of the glyburide, the infant was stable on a regimen of glyburide orally three times a day, and no longer required insulin.
Glyburide, known generically as glibenclamide, is an anti-diabetic drug in a class of medications known as sulfonylureas, used in the treatment of type 2 diabetes.
"Many patients with neonatal diabetes due to KCNJ11 mutations can be treated with oral sulfonylureas, drugs that are typically used to treat individuals with type 2 diabetes," Bremer said.
"This is because most KCNJ11 mutations do not appear to disrupt the ability of the sulfonylureas to bind to their target in the pancreas causing insulin release."
Bremer said that the case study strongly supports the notion that any child diagnosed with diabetes under the age of two deserves a genetic evaluation because, in the event that they do have neonatal diabetes due to specific genetic mutations, they may be amenable to treatment with an oral medication.
Other physicians involved in the case study include pediatric endocrinologists Sayali Ranadive and Robert Lustig of the University of California, San Francisco. UC Davis Children's Hospital is the Sacramento region's only comprehensive hospital for children. From primary care offices to specialty and intensive care clinics, pediatric experts provide compassionate care to more than 100,000 children each year and conduct research on causes and improved treatments for conditions such as autism, asthma, obesity, cancer and birth defects. For more information, visit www.ucdmc.ucdavis.edu/children.