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Pörksen S, Laborie LB, Nielsen L, et al. Disease progression and search for monogenic diabetes among children with new onset type 1 diabetes negative for ICA, GAD- and IA-2 Antibodies. BMC Endocr Disord. 2010;10:16doi: 10.1186/1472-6823-10-16.
Pörksen, S., Laborie, L. B., Nielsen, L., Louise Max Andersen, M., Sandal, T., de Wet, H., Schwarcz, E., Aman, J., Swift, P., Kocova, M., Schönle, E. J., de Beaufort, C., Hougaard, P., Ashcroft, F., Molven, A., Knip, M., Mortensen, H. B., Hansen, L., Njølstad, P. R. (2010). Disease progression and search for monogenic diabetes among children with new onset type 1 diabetes negative for ICA, GAD- and IA-2 Antibodies. BMC endocrine disorders, 1016. https://doi.org/10.1186/1472-6823-10-16
Pörksen, Sven, et al. "Disease progression and search for monogenic diabetes among children with new onset type 1 diabetes negative for ICA, GAD- and IA-2 Antibodies." BMC endocrine disorders vol. 10 (2010): 16. doi: https://doi.org/10.1186/1472-6823-10-16
Pörksen S, Laborie LB, Nielsen L, Louise Max Andersen M, Sandal T, de Wet H, Schwarcz E, Aman J, Swift P, Kocova M, Schönle EJ, de Beaufort C, Hougaard P, Ashcroft F, Molven A, Knip M, Mortensen HB, Hansen L, Njølstad PR. Disease progression and search for monogenic diabetes among children with new onset type 1 diabetes negative for ICA, GAD- and IA-2 Antibodies. BMC Endocr Disord. 2010 Sep 23;10:16. doi: 10.1186/1472-6823-10-16. PMID: 20863361; PMCID: PMC2955624.
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BMC Endocr Disord. 2010 Sep 23;10:16. doi: 10.1186/1472-6823-10-16.

Disease progression and search for monogenic diabetes among children with new onset type 1 diabetes negative for ICA, GAD- and IA-2 Antibodies.

BMC endocrine disorders

Sven Pörksen, Lene Bjerke Laborie, Lotte Nielsen, Marie Louise Max Andersen, Tone Sandal, Heidi de Wet, Erik Schwarcz, Jan Aman, Peter Swift, Mirjana Kocova, Eugen J Schönle, Carine de Beaufort, Philip Hougaard, Frances Ashcroft, Anders Molven, Mikael Knip, Henrik B Mortensen, Lars Hansen, Pål R Njølstad,

Affiliations

  1. Department of Pediatrics, Glostrup Hospital & University of Copenhagen, Copenhagen, Denmark. [email protected].

PMID: 20863361 PMCID: PMC2955624 DOI: 10.1186/1472-6823-10-16

Abstract

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.

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