Reference : Impact of IDDM2 on disease pathogenesis and progression in children with newly diagno...
Scientific journals : Article
Human health sciences : Multidisciplinary, general & others
http://hdl.handle.net/10993/27202
Impact of IDDM2 on disease pathogenesis and progression in children with newly diagnosed type 1 diabetes: Reduced insulin antibody titres and preserved beta cell function
English
Nielsen, L. B. [Department of Paediatrics, Glostrup University Hospital, Ndr. Ringvej 57, DK-2600, Glostrup, Denmark]
Mortensen, H. B. [Department of Paediatrics, Glostrup University Hospital, Ndr. Ringvej 57, DK-2600, Glostrup, Denmark]
Chiarelli, F. [Department of Paediatrics, University of Chieti, Chieti, Italy]
Holl, R. [Department of Mathematics, University of Ulm, Ulm, Germany]
Swift, P. [Department of Paediatrics, Leicester Royal Infirmary Children's Hospital, Leicester, United Kingdom]
De Beaufort, Carine mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Pociot, F. [Steno Diabetes Center, Gentofte, Denmark]
Hougaard, P. [Department of Statistics, University of Southern Denmark, Odense, Denmark]
Gammeltoft, S. [Department of Clinical Biochemistry, Glostrup University Hospital, Glostrup, Denmark]
Knip, M. [Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland]
Hansen, L. [Science and Medicine, Novo Nordisk A/S, Bagsværd, Denmark]
2006
Diabetologia
49
1
71-74
Yes
0012186X
[en] Beta cell function ; IDDM2 ; Insulin antibodies ; Type 1 diabetes ; C peptide ; HLA system ; C-Peptide ; Child ; Diabetes Mellitus, Type 1 ; Follow-Up Studies ; Genetic Predisposition to Disease ; Humans ; Insulin ; Insulin Antibodies ; Insulin-Secreting Cells ; Minisatellite Repeats ; Polymorphism, Single Nucleotide ; Time Factors
[en] Aims/hypothesis: The insulin-dependent diabetes mellitus 2 gene (IDDM2) is a type 1 diabetes susceptibility locus contributed to by the variable number of tandem repeats (VNTR) upstream of the insulin gene (INS). We investigated the association between INS VNTR class III alleles (-23HphIA/T) and both insulin antibody presentation and residual beta cell function during the first year after diagnosis in 257 children with type 1 diabetes. Materials and methods: To estimate C-peptide levels and autoantibody presentation, patients underwent a meal-stimulated C-peptide test 1, 6, and 12 months after diagnosis. The insulin -23HphIA/T variant was used as a marker of class III alleles and genotyped by PCR-RFLP. Results: The insulin antibody titres at 1 and 6 months were significantly lower in the class III/III and class I/III genotype groups than in the class I/I genotype group (p = 0.01). Class III alleles were also associated with residual beta cell function 12 months after diagnosis and independently of age, sex, BMI, insulin antibody titres, and HLA-risk genotype group (p = 0.03). The C-peptide level was twice as high among class III/III genotypes as in class I/I and class I/III genotypes (319 vs 131 and 166 pmol/l, p=0.01). Furthermore, the class III/III genotype had a 1.1% reduction in HbA1c after adjustment for insulin dose (p = 0.04). Conclusions/interpretation: These findings suggest a direct connection in vivo between INS VNTR class III alleles, a decreased humoral immune response to insulin, and preservation of beta cell function in recent-onset type 1 diabetes. © Springer-Verlag 2005.
http://hdl.handle.net/10993/27202
10.1007/s00125-005-0042-1

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