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Sulfonylurea therapy improves neurologic symptoms in children with neonatal diabetes
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Children with certain developmental delays associated with neonatal diabetes showed measurable improvement in their symptoms after switching from insulin therapy to sulfonylurea therapy for 12 months, according to research in Diabetes Care.
In a prospective, single-center study of children successfully switched from insulin to sulfonylurea therapy for 12 months, researchers found that the sulfonylurea glyburide improved central nervous system function in children with permanent or transient neonatal diabetes due to KCNJ11 or ABCC8 mutations.
“The effect seems to target specific brain regions, as the greatest improvements were for cerebellar functions and thalamic functions involved in various steps of gesture conception and realization, such as sensory integration and motor planning,” Jacques Beltrand, MD, PhD, of Necker-Enfants Malades Hospital in Paris, and colleagues wrote.
Beltrand and colleagues analyzed data from 18 children, aged 5 months to 18 years, with neonatal diabetes evaluated between July 2006 and February 2009 (mean age, 5.3 years; 13 boys; mean HbA1c, 7.75%). Children were all switched from insulin therapy to the sulfonylurea therapy glyburide for 12 months. All children underwent MRI at baseline. Muscle tone, gross motor control, body spatial integration and auditory attention tasks were assessed at baseline and 12 months; intellectual performance was evaluated at baseline, 6 months and 12 months. All patients also underwent an electroretinogram; children older than 6 years underwent electrophysiological testing.
Researchers found that metabolic control in the cohort improved after the switch to glyburide therapy; no children experienced hypoglycemia, and one patient experienced remission, discontinuing glyburide after 12 months. HbA1c levels improved by a mean of 1.55% at 12 months.
Within the cohort, 17 children showed developmental coordination disorder, attention-deficit disorder or both at baseline; this was combined with hypotonia in 15 children. After 12 months of glyburide therapy, hypotonia, visual attention deficits, gross and fine motor skills, and gesture conception all improved.
“These abnormalities improved markedly after 12 months of [sulfonylurea therapy],” the researchers wrote. “In young children, tone was closer to the normal for chronological age and attention disorders had resolved, with normalization in gross motor skills in all children but one and of fine motor skills in three children.”
Language disorders, found in six children at baseline, and altered social skills, found in four children younger than 4 years, were not improved after 12 months of therapy, whereas hyperactivity, found in two children at baseline, had resolved after 12 months of therapy, according to researchers. Electrophysiological muscle and nerve tests were normal; baseline MRI detected white matter abnormalities in most children.
“The greater improvements in younger patients indicate a need for establishing the diagnosis early to allow prompt initiation of [sulfonylurea] therapy,” the researchers wrote. “Further follow-up of our patients will provide information about the kinetics of [sulfonylurea] effects on neurodevelopmental parameters.” – by Regina Schaffer
Disclosure: One of the researchers reports being supported by HRA Pharma.
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