Sulfonylurea Therapy Benefits Neurological and Psychomotor Functions in Patients With Neonatal Diabetes Owing to Potassium Channel Mutations.
Details
Serval ID
serval:BIB_7EC2C637743B
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Sulfonylurea Therapy Benefits Neurological and Psychomotor Functions in Patients With Neonatal Diabetes Owing to Potassium Channel Mutations.
Journal
Diabetes care
Working group(s)
GlidKir Study Group
Contributor(s)
Le Tallec C., Ser N., Nivot-Adamiak S., de Kerdanet M., Cartigny M., Weill J., Baron S., Ramos-Caldagues E., Bruel H., Lienhardt-Roussie A., Loeuille G.A., Razafimahefa B., Reynaud R., Simonin G.
ISSN
1935-5548 (Electronic)
ISSN-L
0149-5992
Publication state
Published
Issued date
11/2015
Peer-reviewed
Oui
Volume
38
Number
11
Pages
2033-2041
Language
english
Notes
Publication types: Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
Neonatal diabetes secondary to mutations in potassium-channel subunits is a rare disease but constitutes a paradigm for personalized genetics-based medicine, as replacing the historical treatment with insulin injections with oral sulfonylurea (SU) therapy has been proven beneficial. SU receptors are widely expressed in the brain, and we therefore evaluated potential effects of SU on neurodevelopmental parameters, which are known to be unresponsive to insulin.
We conducted a prospective single-center study. Nineteen patients (15 boys aged 0.1-18.5 years) were switched from insulin to SU therapy. MRI was performed at baseline. Before and 6 or 12 months after the switch, patients underwent quantitative neurological and developmental assessments and electrophysiological nerve and muscle testing.
At baseline, hypotonia, deficiencies in gesture conception or realization, and attention disorders were common. SU improved HbA1c levels (median change -1.55% [range -3.8 to 0.1]; P < 0.0001), intelligence scores, hypotonia (in 12 of 15 patients), visual attention deficits (in 10 of 13 patients), gross and fine motor skills (in all patients younger than 4 years old), and gesture conception and realization (in 5 of 8 older patients). Electrophysiological muscle and nerve tests were normal. Cerebral MRI at baseline showed lesions in 12 patients, suggesting that the impairments were central in origin.
SU therapy in neonatal diabetes secondary to mutations in potassium-channel subunits produces measurable improvements in neuropsychomotor impairments, which are greater in younger patients. An early genetic diagnosis should always be made, allowing for a rapid switch to SU.
We conducted a prospective single-center study. Nineteen patients (15 boys aged 0.1-18.5 years) were switched from insulin to SU therapy. MRI was performed at baseline. Before and 6 or 12 months after the switch, patients underwent quantitative neurological and developmental assessments and electrophysiological nerve and muscle testing.
At baseline, hypotonia, deficiencies in gesture conception or realization, and attention disorders were common. SU improved HbA1c levels (median change -1.55% [range -3.8 to 0.1]; P < 0.0001), intelligence scores, hypotonia (in 12 of 15 patients), visual attention deficits (in 10 of 13 patients), gross and fine motor skills (in all patients younger than 4 years old), and gesture conception and realization (in 5 of 8 older patients). Electrophysiological muscle and nerve tests were normal. Cerebral MRI at baseline showed lesions in 12 patients, suggesting that the impairments were central in origin.
SU therapy in neonatal diabetes secondary to mutations in potassium-channel subunits produces measurable improvements in neuropsychomotor impairments, which are greater in younger patients. An early genetic diagnosis should always be made, allowing for a rapid switch to SU.
Keywords
Administration, Oral, Adolescent, Brain/pathology, Child, Child, Preschool, Diabetes Mellitus/drug therapy, Diabetes Mellitus/genetics, Diabetes Mellitus/physiopathology, Drug Substitution, Female, Glyburide/administration & dosage, Glyburide/therapeutic use, Humans, Hypoglycemic Agents/administration & dosage, Hypoglycemic Agents/therapeutic use, Infant, Infant, Newborn, Insulin/administration & dosage, Insulin/therapeutic use, Magnetic Resonance Imaging, Male, Mutation, Neurologic Manifestations, Neuropsychological Tests, Potassium Channels, Inwardly Rectifying/genetics, Psychomotor Performance, Sulfonylurea Receptors/genetics
Pubmed
Web of science
Open Access
Yes
Create date
28/02/2020 17:06
Last modification date
26/03/2020 7:26