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Sulfonylurea Therapy Over Insulin Benefits Neurodevelopment

Improvements seen in children with developmental delays associated with neonatal diabetes.

Neonatal diabetes is a rare disease caused by mutations in potassium-channel subunits. This disease creates a model for personalized genetics-based medicine. However, historical treatment with insulin injections and oral sulfonylurea therapy has been proven effective. Therefore, researchers wanted to examine the potential benefit of sulfonylurea therapy on neurodevelopment since sulfonylurea receptors are widely expressed in the brain.

Researcher Jacques Beltrand, MD, PhD, and colleagues conducted a prospective, single-center study of children who were successfully switched from insulin to sulfonylurea therapy with glyburide for 12 months. Researchers analyzed data from 18 children, aged 5 months to 18 years, with neonatal diabetes evaluated between July 2006 and February 2009. These subjects had an average age of 5 years, there were 13 boys, and average HbA1c was close to 8%.

In this study, all children had an MRI performed at baseline. Muscle tone, gross motor control, body spatial integration and auditory attention tasks were assessed initially and at 12 months. Furthermore, intellectual performance was examined at baselines, 6 months, and at 12 months. All patients underwent electroretinogram, and children greater than 6 years old underwent electrophysiological testing.

Researchers found improvement in metabolic control once patients were switched to glyburide therapy, where no children had incidents of hypoglycemia. One patient experienced remission, who discontinued glyburide after 12 months. It was also found that HbA1c levels improved by an average of 1.5% at 12 months. In this study, coordination disorder, attention-deficit disorder or both was present in 17 children at baseline. This was combined with hypotonia in 15 children. Once glyburide therapy was utilized for 12 months, improvement in all areas was observed, including hypotonia, visual attention deficits, gross and fine motor skills, and gesture conception.

Authors believe that sulfonylurea therapy in neonatal diabetes secondary to metabolic mutations produces measureable improvements in neuropsychomotor impairments. However, children suffering from this condition should be diagnosed as early as possible to facilitate the switch from insulin to sulfonylurea.

Practice Pearls:

  • Sulfonylurea therapy provides measurable improvements in neuropsychomotor impairments, which are greater in younger patients due to neonatal diabetes.
  • An early genetic diagnosis should be made to allow for rapid switch to sulfonylurea.
  • Further follow-up studies are warranted to recognize information about the kinetics of sulfonylurea effects on neurodevelopmental parameters.

Beltrand, Jacques, et al. “Sulfonylurea Therapy Benefits Neurological and Psychomotor Functions in Patients With Neonatal Diabetes Owing to Potassium Channel Mutations.” doi: 10.2337/dc15-0837 Diabetes Care October 5, 2015