ESPE Abstracts (2022) 95 P1-286

ESPE2022 Poster Category 1 Fetal, Neonatal Endocrinology and Metabolism (30 abstracts)

Sulphonylurea for Improving Neurological Features in Neonatal Diabetes: a systematic review and meta-analyses

Caroline de Gouveia Buff Passone 1,2,3,4,5 , Elisa Giani 1,2,3,5,6 , Laurence Vaivre-Douret 2,7 , Dulandjalee Karayawasam 1,2,5 , Marianne Berdugo 8 , Laure Garcin 1 , Jacques Beltrand 1,2,3,5, , Wanderley Marques Bernardo 4 & Michel Polak 1,2,3,5,9


1Hôpital Necker Enfants Malades, APHP Centre, Endocrinologie, Gynécologie et Diabétologie Pédiatrique, Paris, France; 2Université Paris Cîté, Paris, France; 3Centre Maladies Rares PRISIS, Paris, France; 4University of Sao Paolo, Sao Paolo, Brazil; 5Inserm U1016, Paris, France; 6Department of Biomedical Sciences, Humanitas University, Milan, Italy; 7INSERM UMR 1018-CESP, Paris, France; 8Physiopathology of Ocular Diseases: Therapeutic Innovations, Sorbonne-Université and Université de Paris, Inserm UMRS 1138, Paris, France; 9Institut Imagine, Paris, France

Background: In monogenic diabetes due to KCNJ11 and ABCC8 mutations that impair KATP- channel function, sulphonylureas improve long-term glycaemic control. Although KATP channels are extensively expressed in the brain, the effect of sulphonylureas on neurological function has varied widely. We evaluated published evidence about potential effects of sulphonylureas on neurological features, especially epilepsy, cognition, motor function and muscular tone, visuo-motor integration, and attention deficits in children and adults with KCNJ11 and ABCC8-related neonatal-onset diabetes mellitus.

Methods: We conducted a systematic review and meta-analyses of the literature (PROSPERO, CRD42021254782), including individual-patient data, according to PRISMA, using RevMan software. We also graded the level ofevidence.

Results: We selected 34 of 776 publications. The evaluation of global neurological function before and after sulphonylurea (glibenclamide) treatment in 114 patients yielded a risk difference (RD) of 58% (95%CI, 43%–74%; I2= 54%) overall and 73% (95%CI, 32%–113%; I2=0%) in the subgroup younger than 4 years; the level of evidence was moderate and high, respectively. EEG studies of epilepsy showed a RD of 56% (95%CI, 23%–89%; I2= 34%) in patients with KCNJ11 mutations, with a high quality of evidence. For hypotonia and motor function, the RDs were 90% (95%CI, 69%–111%; I2=0%) and 73% (95%CI, 35%–111%; I2=0%), respectively, with a high level of evidence. Visuomotor coordination seemed improved by sulphonylurea therapy, similarly to ADHD, which is extraordinarily prevalent in patients with KATP-channel mutations.

Conclusion: Glibenclamide significantly improved neurological abnormalities in patients with neonatal-onsetdiabetes due to KCNJ11 or ABCC8 mutations. Hypotonia was the symptom that responded best. Earlier treatment initiation was associated with greater benefits. Diagnosing neonatal diabetes and KATP- channel mutations early is therefore a major goal.

Keywords: Neurological disorders. Sulphonylurea. Neonatal diabetes. Epilepsy. Mental development. Motor development. Attention-deficit disorders.

Volume 95

60th Annual ESPE (ESPE 2022)

Rome, Italy
15 Sep 2022 - 17 Sep 2022

European Society for Paediatric Endocrinology 

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