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dc.contributor.authorPörksen, Svenen_US
dc.contributor.authorLaborie, Lene Bjerkeen_US
dc.contributor.authorNielsen, Lotteen_US
dc.contributor.authorAndersen, Marie Louise Maxen_US
dc.contributor.authorSandal, Toneen_US
dc.contributor.authorde Wet, Heidien_US
dc.contributor.authorSchwarcz, Eriken_US
dc.contributor.authorÅman, Janen_US
dc.contributor.authorSwift, Peteren_US
dc.contributor.authorKocova, Mirjanaen_US
dc.contributor.authorSchönle, Eugen J.en_US
dc.contributor.authorde Beaufort, Carineen_US
dc.contributor.authorHougaard, Philipen_US
dc.contributor.authorAshcroft, Francesen_US
dc.contributor.authorMolven, Andersen_US
dc.contributor.authorKnip, Mikaelen_US
dc.contributor.authorMortensen, Henrik B.en_US
dc.contributor.authorHansen, Larsen_US
dc.contributor.authorNjølstad, Pål Rasmusen_US
dc.contributor.authorHvidøre Study Group on Childhood Diabetesen_US
dc.date.accessioned2014-10-24T12:40:49Z
dc.date.available2014-10-24T12:40:49Z
dc.date.issued2010-09-23eng
dc.identifier.issn1472-6823
dc.identifier.urihttps://hdl.handle.net/1956/8673
dc.description.abstractBackground: To investigate disease progression the first 12 months after diagnosis in children with type 1 diabetes negative (AAB negative) for pancreatic autoantibodies [islet cell autoantibodies(ICA), glutamic acid decarboxylase antibodies (GADA) and insulinoma-associated antigen-2 antibodies (IA-2A)]. Furthermore the study aimed at determining whether mutations in KCNJ11, ABCC8, HNF1A, HNF4A or INS are common in AAB negative diabetes. Materials and methods: In 261 newly diagnosed children with type 1 diabetes, we measured residual b-cell function, ICA, GADA, and IA-2A at 1, 6 and 12 months after diagnosis. The genes KCNJ11, ABCC8, HNF1A, HNF4A and INS were sequenced in subjects AAB negative at diagnosis. We expressed recombinant K-ATP channels in Xenopus oocytes to analyse the functional effects of an ABCC8 mutation. Results: Twenty-four patients (9.1%) tested AAB negative after one month. Patients, who were AAB-negative throughout the 12-month period, had higher residual b-cell function (P = 0.002), lower blood glucose (P = 0.004), received less insulin (P = 0.05) and had lower HbA1c (P = 0.02) 12 months after diagnosis. One patient had a heterozygous mutation leading to the substitution of arginine at residue 1530 of SUR1 (ABCC8) by cysteine. Functional analyses of recombinant K-ATP channels showed that R1530C markedly reduced the sensitivity of the KATP channel to inhibition by MgATP. Morover, the channel was highly sensitive to sulphonylureas. However, there was no effect of sulfonylurea treatment after four weeks on 1.0-1.2 mg/kg/24 h glibenclamide. Conclusion: GAD, IA-2A, and ICA negative children with new onset type 1 diabetes have slower disease progression as assessed by residual beta-cell function and improved glycemic control 12 months after diagnosis. One out of 24 had a mutation in ABCC8, suggesting that screening of ABCC8 should be considered in patients with AAB negative type 1 diabetes.en_US
dc.language.isoengeng
dc.publisherBioMed Centraleng
dc.rightsAttribution CC BYeng
dc.rights.urihttp://creativecommons.org/licenses/by/2.0eng
dc.titleDisease progression and search for monogenic diabetes among children with new onset type 1 diabetes negative for ICA, GAD- and IA-2 Antibodiesen_US
dc.typePeer reviewed
dc.typeJournal article
dc.date.updated2013-08-28T16:15:56Z
dc.description.versionpublishedVersionen_US
dc.rights.holderCopyright 2010 Pörksen et al; licensee BioMed Central Ltd.
dc.rights.holderSven Pörksen et al.; licensee BioMed Central Ltd.
dc.source.articlenumber16
dc.identifier.doihttps://doi.org/10.1186/1472-6823-10-16
dc.identifier.cristin531672
dc.source.journalBMC Endocrine Disorders
dc.source.4010


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