Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

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

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Pörksen, S, Laborie, L, Nielsen, L, Louise Max Andersen, M, Sandal, T, de Wet, H, Schwarcz, E, +man, J, Swift, P, Kocova, M, Schönle, E, de Beaufort, C, Hougaard, P, Ashcroft, F, Molven, A, Knip, M, Mortensen, HB, Hansen, L, Njølstad, P & Diabetes, HSGOC 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 Endocr Disord., vol. 10, no. 1, pp. 16.

APA

CBE

Pörksen S, Laborie L, Nielsen L, Louise Max Andersen M, Sandal T, de Wet H, Schwarcz E, +man J, Swift P, Kocova M, Schönle E, de Beaufort C, Hougaard P, Ashcroft F, Molven A, Knip M, Mortensen HB, Hansen L, Njølstad P, Diabetes HSGOC. 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 Endocr Disord. 10(1):16.

MLA

Vancouver

Author

Pörksen, Sven ; Laborie, Lene ; Nielsen, Lotte ; Louise Max Andersen, Marie ; Sandal, Tone ; de Wet, Heidi ; Schwarcz, Erik ; +man, Jan ; Swift, Peter ; Kocova, Mirjana ; Schönle, Eugen ; de Beaufort, Carine ; Hougaard, Philip ; Ashcroft, Frances ; Molven, Anders ; Knip, Mikael ; Mortensen, Henrik Bindesbøl ; Hansen, Lars ; Njølstad, Pål ; Diabetes, Hvidøre Study Group on Childhood. / Disease progression and search for monogenic diabetes among children with new onset type 1 diabetes negative for ICA, GAD- and IA-2 Antibodies. In: BMC Endocr Disord. 2010 ; Vol. 10, No. 1. pp. 16.

Bibtex

@article{ecc92492705d411e9a33826b7fcc8812,
title = "Disease progression and search for monogenic diabetes among children with new onset type 1 diabetes negative for ICA, GAD- and IA-2 Antibodies",
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 {\^i}-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 {\^i}-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",
author = "Sven P{\"o}rksen and Lene Laborie and Lotte Nielsen and {Louise Max Andersen}, Marie and Tone Sandal and {de Wet}, Heidi and Erik Schwarcz and Jan +man and Peter Swift and Mirjana Kocova and Eugen Sch{\"o}nle and {de Beaufort}, Carine and Philip Hougaard and Frances Ashcroft and Anders Molven and Mikael Knip and Mortensen, {Henrik Bindesb{\o}l} and Lars Hansen and P{\aa}l Nj{\o}lstad and Diabetes, {Hvid{\o}re Study Group on Childhood}",
year = "2010",
language = "English",
volume = "10",
pages = "16",
journal = "BMC Endocrine Disorders",
issn = "1472-6823",
publisher = "BioMed Central Ltd",
number = "1",

}

RIS

TY - JOUR

T1 - Disease progression and search for monogenic diabetes among children with new onset type 1 diabetes negative for ICA, GAD- and IA-2 Antibodies

AU - Pörksen, Sven

AU - Laborie, Lene

AU - Nielsen, Lotte

AU - Louise Max Andersen, Marie

AU - Sandal, Tone

AU - de Wet, Heidi

AU - Schwarcz, Erik

AU - +man, Jan

AU - Swift, Peter

AU - Kocova, Mirjana

AU - Schönle, Eugen

AU - de Beaufort, Carine

AU - Hougaard, Philip

AU - Ashcroft, Frances

AU - Molven, Anders

AU - Knip, Mikael

AU - Mortensen, Henrik Bindesbøl

AU - Hansen, Lars

AU - Njølstad, Pål

AU - Diabetes, Hvidøre Study Group on Childhood

PY - 2010

Y1 - 2010

N2 - 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 î-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 î-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

AB - 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 î-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 î-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

M3 - Journal article

VL - 10

SP - 16

JO - BMC Endocrine Disorders

JF - BMC Endocrine Disorders

SN - 1472-6823

IS - 1

ER -

ID: 32320835