Reference : Disease progression and search for monogenic diabetes among children with new onset t...
Scientific journals : Article
Human health sciences : Multidisciplinary, general & others
http://hdl.handle.net/10993/27181
Disease progression and search for monogenic diabetes among children with new onset type 1 diabetes negative for ICA, GAD- and IA-2 Antibodies
English
Pörksen, S. [Department of Pediatrics, Glostrup Hospital and University of Copenhagen, Copenhagen, Denmark]
Laborie, L. B. [Department of Clinical Medicine, University of Bergen, Bergen, Norway, Department of Pediatrics, Haukeland University Hospital, Bergen, Norway]
Nielsen, L. [Department of Pediatrics, Glostrup Hospital and University of Copenhagen, Copenhagen, Denmark]
Louise Max Andersen, M. [Department of Pediatrics, Glostrup Hospital and University of Copenhagen, Copenhagen, Denmark]
Sandal, T. [Department of Clinical Medicine, University of Bergen, Bergen, Norway, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway, Gade Institute, University of Bergen, Bergen, Norway]
de Wet, H. [Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom]
Schwarcz, E. [Department of Pediatrics, University Hospital Ørebro, Ørebro, Sweden]
Åman, J. [Department of Pediatrics, University Hospital Ørebro, Ørebro, Sweden]
Swift, P. [Department of Pediatrics, Leicester Royal Infirmery Children's Hospital, Leicester, United Kingdom]
Kocova, M. [Department of Endocrinology and Genetics, Paediatric Clinic, Skopje, Macedonia]
Schönle, E. J. [Department of Pediatrics, University Childrens Hospital, Zurich, Switzerland]
De Beaufort, Carine mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Hougaard, P. [Department of Biostatistics, University of Southern Denmark, Odense, Denmark]
Ashcroft, F. [Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom]
Molven, A. [Gade Institute, University of Bergen, Bergen, Norway]
Knip, M. [Department of Pediatrics, Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland]
Mortensen, H. B. [Department of Pediatrics, Glostrup Hospital and University of Copenhagen, Copenhagen, Denmark]
Hansen, L. [Department of Pediatrics, Glostrup Hospital and University of Copenhagen, Copenhagen, Denmark]
Njølstad, P. R. [Department of Clinical Medicine, University of Bergen, Bergen, Norway, Department of Pediatrics, Haukeland University Hospital, Bergen, Norway]
2010
BMC Endocrine Disorders
10
Yes (verified by ORBilu)
14726823
[en] ABC transporter ; Xenopus ; disease progression ; monogenic diabetes ; type 1 diabetes ; ICA ; GAD ; IA-2 ; antibodies
[en] Background: 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 β-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 β-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 K-ATP 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. © 2010 Pörksen et al; licensee BioMed Central Ltd.
http://hdl.handle.net/10993/27181
10.1186/1472-6823-10-16

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